Survivorship

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)
Survivorship
Version 2.2020 — July 14, 2020
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Version 2.2020, 07/14/20 © 2020 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
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NCCN Guidelines Version 2.2020 NCCN Guidelines Index

Table of Contents
Survivorship Discussion
*Crystal S. Denlinger, MD/Chair † Melissa Hudson, MD € ‡ † Tracey O’Connor, MD † Lillie Shockney, RN, MAS # ¶
Fox Chase Cancer Center St. Jude Children's Research Roswell Park Cancer Institute The Sidney Kimmel Comprehensive
*Tara Sanft, MD/Vice-Chair † Þ Hospital/The University of Tennessee *Linda Overholser, MD, MPH Þ Cancer Center at Johns Hopkins
Yale Cancer Center/ Health Science Center University of Colorado Sophia Smith, PhD, MSW £
Smilow Cancer Hospital Nazanin Khakpour, MD ¶ Cancer Center Duke Cancer Institute
Saro Armenian, DO, MPH € Moffitt Cancer Center *Electra D. Paskett, PhD ɛ *Karen L. Syrjala, PhD q £
City of Hope Divya Koura, MD ‡ ξ The Ohio State University Fred Hutchinson Cancer
National Medical Center UC San Diego Comprehensive Cancer Center - Research Center/Seattle
K. Scott Baker, MD, MS € ξ Moores Cancer Center James Cancer Hospital and Solove Cancer Care Alliance
Fred Hutchinson Cancer Allison L. McDonough, MD Þ Research Institute Amye Tevaarwerk, MD ‡
Research Center/ Massachusetts General Hospital Chirayu Patel, MD, MPH § University of Wisconsin
Seattle Cancer Care Alliance Cancer Center Massachusetts General Hospital Carbone Cancer Center
Gregory Broderick, MD w Michelle Melisko, MD † £ Cancer Center Phyllis Zee, MD, PhD ɛ ψ
Mayo Clinic Cancer Center UCSF Helen Diller Family Lindsay Peterson, MD † Robert H. Lurie Comprehensive
Wendy Demark-Wahnefried, PhD, RD ≅ Comprehensive Cancer Center Siteman Cancer Center at Barnes- Cancer Center of Northwestern
O’Neal Comprehensive *Kathi Mooney, RN, PhD # † Jewish Hospital and Washington University
Cancer Center at UAB Huntsman Cancer Institute University School of Medicine
Kristin Dickinson, PhD, RN § at the University of Utah *William Pirl, MD q NCCN

Fred & Pamela Buffett Cancer Halle C. F. Moore, MD † Dana-Farber/Brigham and Women's Deborah Freedman-Cass, PhD
Center Case Comprehensive Cancer Cancer Center Nicole McMillian, MS
Debra L. Friedman, MD, MS € ‡ † Center/University Hospitals Seidman *M. Alma Rodriguez, MD ‡ † Þ

Vanderbilt-Ingram Cancer Center Cancer Center and Cleveland Clinic The University of Texas
Taussig Cancer Institute MD Anderson Cancer Center
Mindy Goldman, MD Ω
UCSF Helen Diller Family Natalie Moryl, MD Þ £ Kathryn J. Ruddy, MD, MPH ‡ †
Comprehensive Cancer Center Memorial Sloan Kettering Mayo Clinic Cancer Center
Cancer Center
Norah Lynn Henry, MD, PhD †
University of Michigan *Javid J. Moslehi, MD l Þ
Rogel Cancer Center Vanderbilt-Ingram Cancer Center ξ Bone marrow transplantation q Psychiatry, psychology, including
l Cardiology health behavior
Christine Hill-Kayser, MD € ‡ ɛ Epidemiology § Radiotherapy/Radiation
Abramson Cancer Center at the Ω Gynecology/Gynecologic oncology
University of Pennsylvania oncology £ Supportive care including
‡ Hematology/Hematology palliative, pain management,
oncology pastoral care, and oncology
Continue Þ Internal medicine
† Medical oncology
social work
¶ Surgery/Surgical oncology
ψ Neurology/Neuro-oncology w Urology
# Nursing *Discussion Section Writing
≅ Nutrition science/Dietitian Committee
NCCN Guidelines Panel Disclosures € Pediatric oncology

Table of Contents
Survivorship Sub-Committees
Cardiovascular Disease Risk Assessment Anxiety, Depression, Trauma, and Distress Cognitive Function
and Anthracycline-Induced Cardiac Toxicity Karen L. Syrjala, PhD/Lead q £ William Pirl, MD q/Lead
Javid J. Moslehi, MD/Lead Þ Fred Hutchinson Cancer Research Center/ Dana-Farber/Brigham and
Vanderbilt-Ingram Cancer Center Seattle Cancer Care Alliance Women's Cancer Center
Saro Armenian, DO, MPH € Crystal Denlinger, MD † K. Scott Baker, MD, MS € ξ
City of Hope Fox Chase Cancer Center Fred Hutchinson Cancer Research
National Medical Center Norah Lynn Henry, MD, PhD † Center/Seattle
K. Scott Baker, MD, MS € ξ University of Michigan Rogel Cancer Center Cancer Care Alliance
Fred Hutchinson Cancer Research Center/ Kathi Mooney, RN, PhD # † Debra L. Friedman, MD, MS € ‡ †
Seattle Cancer Care Alliance Huntsman Cancer Institute Vanderbilt-Ingram Cancer Center
Crystal S. Denlinger, MD † at the University of Utah Michelle Melisko, MD † £
Fox Chase Cancer Center William Pirl, MD q UCSF Helen Diller Family
Melissa Hudson, MD € ‡ † Dana-Farber/Brigham and Women's Cancer Center Comprehensive Cancer Center
St. Jude Children's Research Hospital/The Lillie Shockney, RN, MAS # ¶ Halle C. F. Moore, MD †
University of Tennessee Health Science The Sidney Kimmel Comprehensive Case Comprehensive Cancer
Center Cancer Center at Johns Hopkins Center/University Hospitals
Divya Koura, MD ‡ ξ Seidman Cancer Center and
Sophia Smith, PhD, MSW £ Cleveland Clinic Taussig Cancer
UC San Diego Moores Cancer Center Duke Cancer Institute Institute
Halle C. F. Moore, MD †
Case Comprehensive Cancer Center/
University Hospitals Seidman Cancer
Center and Cleveland Clinic Taussig
Cancer Institute
Linda Overholser, MD, MPH Þ
University of Colorado Cancer Center
Chirayu Patel, MD, MPH § ξ Bone marrow transplantation q Psychiatry, psychology,
Massachusetts General Hospital Cancer l Cardiology including health behavior
‡ Hematology/Hematology § Radiotherapy/Radiation
Center oncology oncology
Kathryn J. Ruddy, MD, MPH ‡ † Þ Internal medicine £ Supportive care including
† Medical oncology palliative, pain management,
Mayo Clinic Cancer Center # Nursing pastoral care, and oncology
Tara Sanft, MD † Þ Continue € Pediatric oncology social work
Yale Cancer Center/
Smilow Cancer Hospital NCCN Guidelines Panel Disclosures

Table of Contents
Fatigue Lymphedema Hormone-Related Symptoms Pain
Kathi Mooney, RN, PhD # †/Lead Electra D. Paskett, PhD ɛ/Lead Mindy Goldman, MD/Lead Ω Natalie Moryl, MD Þ £/Lead
Huntsman Cancer Institute The Ohio State University UCSF Helen Diller Family Memorial Sloan Kettering Cancer
at the University of Utah Comprehensive Cancer Center- Comprehensive Cancer Center Center
Debra L. Friedman, MD, MS € ‡ † James Cancer Hospital and Gregory Broderick, MD w Debra L. Friedman, MD, MS ‡ †
Vanderbilt-Ingram Cancer Center Solove Research Institute Mayo Clinic Cancer Center Vanderbilt-Ingram
Allison L. McDonough, MD Þ Nazanin Khakpour, MD ¶ Norah Lynn Henry, MD, PhD † Cancer Center
Massachusetts General Hospital Moffitt Cancer Center University of Michigan Norah Lynn Henry, MD, PhD †
Cancer Center Halle C. F. Moore, MD † Rogel Cancer Center University of Michigan
Michelle Melisko, MD † £ Case Comprehensive Cancer Michelle Melisko, MD † £ Rogel Cancer Center
UCSF Helen Diller Family Center/University Hospitals UCSF Helen Diller Family Tara Sanft, MD † Þ
Comprehensive Cancer Center Seidman Cancer Center and Comprehensive Cancer Center Yale Cancer Center/Smilow
Cleveland Clinic Taussig Cancer Hospital
Tracey O’Connor, MD † Cancer Institute Halle C. F. Moore, MD †
Roswell Park Cancer Institute Case Comprehensive Cancer Karen L. Syrjala, PhD q £
Tracey O’Connor, MD † Center/University Hospitals Fred Hutchinson Cancer
Tara Sanft, MD † Þ Roswell Park Cancer Institute
Yale Cancer Center/ Seidman Cancer Center and Research Center/Seattle Cancer
Smilow Cancer Hospital Cleveland Clinic Taussig Care Alliance
Cancer Institute Amye Tevaarwerk, MD ‡
Tracey O’Connor, MD † University of Wisconsin
Roswell Park Cancer Institute Carbone Cancer Center
Electra D. Paskett, PhD ɛ
The Ohio State University
Comprehensive Cancer Center-
James Cancer Hospital and
Solove Research Institute
Amye Tevaarwerk, MD ‡
University of Wisconsin
Carbone Cancer Center
ɛ Epidemiology q Psychiatry, psychology,

‡ Hematology/Hematology including health behavior
Continue oncology
Þ Internal medicine
£ Supportive care
including palliative, pain
† Medical oncology management, pastoral care,
# Nursing and oncology social work
€ Pediatric oncology ¶ Surgery/Surgical oncology
NCCN Guidelines Panel Disclosures w Urology

Table of Contents
Sexual Function Sleep Disorders Second Cancers
Mindy Goldman, MD/Co-Lead Ω Phyllis Zee, MD, PhD/Lead ɛ ψ Linda Overholser, MD, MPH Þ/Lead
UCSF Helen Diller Family Robert H. Lurie Comprehensive Cancer University of Colorado
Comprehensive Cancer Center Center of Northwestern University Cancer Center
Gregory Broderick, MD/Co-Lead w Halle C. F. Moore, MD † Crystal S. Denlinger, MD †
Mayo Clinic Cancer Center Case Comprehensive Cancer Center/ Fox Chase Cancer Center
Norah Lynn Henry, MD, PhD † University Hospitals Seidman Cancer Center Debra L. Friedman, MD, MS € ‡ †
University of Michigan and Cleveland Clinic Taussig Cancer Institute Vanderbilt-Ingram Cancer Center
Rogel Cancer Center Tracey O’Connor, MD † Divya Koura, MD ‡ ξ
Michelle Melisko, MD † £ Roswell Park Cancer Institute UC San Diego
UCSF Helen Diller Family Tara Sanft, MD † Þ Moores Cancer Center
Comprehensive Cancer Center Yale Cancer Center/Smilow Cancer Hospital Norah Lynn Henry, MD, PhD †
Halle C. F. Moore, MD † University of Michigan Rogel Cancer Center
Case Comprehensive Cancer Center/ Immunizations and Infections Halle C. F. Moore, MD †
University Hospitals Seidman Cancer Case Comprehensive Cancer Center/University
Center and Cleveland Clinic Taussig M. Alma Rodriguez, MD ‡ † Þ/Lead
The University of Texas Hospitals Seidman Cancer Center and Cleveland
Cancer Institute Clinic Taussig Cancer Institute
MD Anderson Cancer Center
Kathryn J. Ruddy, MD, MPH ‡ †
Mayo Clinic Cancer Center K. Scott Baker, MD, MS € ξ
Fred Hutchinson Cancer Research Center/
Lillie Shockney, RN, MAS # ¶ Seattle Cancer Care Alliance
The Sidney Kimmel Comprehensive
Cancer Center at Johns Hopkins Melissa Hudson, MD € ‡ †
St. Jude Children's Research Hospital/
Amye Tevaarwerk, MD ‡ The University of Tennessee Health Science
University of Wisconsin Center
Carbone Cancer Center
Divya Koura, MD ‡ ξ
UC San Diego Moores Cancer Center
ξ Bone marrow transplantation # Nursing

Continue Ω Gynecology/Gynecologic
oncology
€ Pediatric oncology
£S upportive care including
‡ Hematology/Hematology palliative, pain management,
oncology pastoral care, and oncology
Þ Internal medicine social work
† Medical oncology ¶ Surgery/Surgical oncology
ψ Neurology/Neuro-oncology w Urology
NCCN Guidelines Panel Disclosures

Table of Contents
Healthy Lifestyles Halle C. F. Moore, MD †

Crystal Denlinger, MD/Lead † Case Comprehensive Cancer Center/
Fox Chase Cancer Center University Hospitals Seidman Cancer
Center and Cleveland Clinic Taussig
Saro Armenian, DO, MPH € Cancer Institute
City of Hope National Medical Center
Wendy Demark-Wahnefried, PhD, RD ≅ Linda Overholser, MD, MPH Þ
O’Neal Comprehensive University of Colorado Cancer Center
Cancer Center at UAB
Electra D. Paskett, PhD ɛ
Melissa Hudson, MD € ‡ † The Ohio State University Comprehensive
St. Jude Children's Research Hospital/The Cancer Center -
University of Tennessee Health Science James Cancer Hospital and
Center Solove Research Institute
Nazanin Khakpour, MD ¶ Lindsay Peterson, MD †
Moffitt Cancer Center Siteman Cancer Center at Barnes-
Michelle Melisko, MD † £ Jewish Hospital and Washington
UCSF Helen Diller Family University School of Medicine
Comprehensive Cancer Center Tara Sanft, MD † Þ
Yale Cancer Center/
Smilow Cancer Hospital
Continue ɛ Epidemiology € Pediatric oncology

‡ Hematology/Hematology £S upportive care including
oncology palliative, pain management,
Þ Internal medicine pastoral care, and oncology
† Medical oncology social work
≅ Nutrition science/Dietitian ¶ Surgery/Surgical oncology
NCCN Guidelines Panel Disclosures

Table of Contents
NCCN Survivorship Panel Members

NCCN Survivorship Sub-Committee Members Clinical Trials: NCCN believes that
the best management for any patient
Summary of the Guidelines Updates
with cancer is in a clinical trial.
General Survivorship Principles Participation in clinical trials is
• Definition of Survivorship & Standards for Survivorship Care (SURV-1) especially encouraged.
• General Principles of the Survivorship Guidelines (SURV-2)
• Screening for Subsequent New Primary Cancers (SURV-3) To find clinical trials online at NCCN
• Assessment By Health Care Provider at Regular Intervals (SURV-4) Member Institutions, click here:
nccn.org/clinical_trials/member_
• Survivorship Assessment (SURV-A)
institutions.aspx.
• Survivorship Resources For Health Care Professionals And Patients (SURV-B)
Preventive Health NCCN Categories of Evidence and
• Healthy Lifestyles (HL-1) Consensus: All recommendations
Physical Activity (SPA-1) are category 2A unless otherwise
Nutrition and Weight Managment (SNWM-1) indicated.
Supplement Use (SSUP-1) See NCCN Categories of Evidence
• Immunizations and Infections (SIMIN-1) and Consensus.
Late Effects/Long-Term Psychosocial and Physical Problems
• Cardiovascular Disease Risk Assessment (SCVD-1)
• Anthracycline-Induced Cardiac Toxicity (SCARDIO-1)
• Anxiety, Depression, Trauma, and Distress (SANXDE-1)
• Cognitive Function (SCF-1)
• Fatigue (SFAT-1)
• Lymphedema (SLYMPH-1)
• Hormone-Related Symptoms (SMP-1)
• Pain (SPAIN-1)
• Sexual Function (SSF-1)
Female Treatment Options (SSF-2)
Male Treatment Options (SSF-3)
• Sleep Disorders (SSD-1)
The NCCN Guidelines® are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to
treatment. Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual
clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes no representations
or warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCN
Guidelines are copyrighted by National Comprehensive Cancer Network®. All rights reserved. The NCCN Guidelines and the illustrations herein may not
be reproduced in any form without the express written permission of NCCN. ©2020.

Table of Contents
Updates in Version 2.2020 of the NCCN Guidelines for Survivorship from Version 1.2020 include:
MS-1
• The Discussion has been updated to reflect the changes in the algorithm.
Updates in Version 1.2020 of the NCCN Guidelines for Survivorship from Version 2.2019 include:
Global Changes
• New algorithm added for Cardiovascular Disease Risk Assessment (SCVD-1 and SCVD-2)
GENERAL SURVIVORSHIP PRINCIPLES
SURV-1
• Standards for Survivorship Care
Care of the cancer survivor should include
◊ Point #3 revised: Assessment of late psychosocial, and physical, and immunologic effects
◊ Point #6 and following sub-bullets revised:
– Survivorship care Planning for ongoing survivorship care
– Removed: Develop and provide to survivor and key health care providers a survivorship care plan that includes:
– Summary of Information on treatment received including all surgeries, radiation therapy, and systemic therapies
– Information on post-treatment needs, including information regarding acute, late, and long-term treatment-related side effects and
health risks when possible (See NCCN Guidelines for Treatment of Cancer by Site)
• References and links were updated for footnotes a, c, and d.
• Footnote reference removed: Mayer DK, Nekhlyudov L, Snyder CF, et al. American society of clinical oncology clinical expert statement on
cancer survivorship care planning. J Oncol Pract 2014;10:345-351.
SURV-3 Screening for Subsequent New Primary Cancers

• Bullets 7-9 were extensively revised.
• Last bullet revised: Criteria for genetic risk assessment and testing, and for management recommendations for of patients with known
germline mutations linked to an increased risk for cancer can be found in the following NCCN Guidelines:
SURV-A Survivorship Assessment (Patient Version)

• Healthy Lifestyle: Question revised, "Do you take vitamins or other supplements?"
SURV-B Survivorship Resources for Health Care Professionals and Patients

• New sections were added for:
Information About LGBTQ Individuals with Cancer
Menopause and Sexual Health
• Suicide Prevention and Other Psychosocial Issues: New resource added, Anxiety and Depression Association of America
• Outdated links were removed.
Continued
Version 2.2020, 07/14/20 © 2020 National Comprehensive Cancer Network (NCCN ), All rights reserved. NCCN Guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
® ® ®
UPDATES

Table of Contents
PREVENTIVE HEALTH
Healthy Lifestyles
HL-1 General Principles
• Under the second bullet; the following arrow sub-bullets were revised:
"Engage in physical activity (eg, exercise, taking the stairs..."
"...and whole grains and low in excess sugars, fried foods, and fats and red and processed meat"
Avoid use or stop using cigarette/tobacco products.
• Third bullet revised: "Obtain nutrients should be obtained from food sources rather than relying on dietary supplements. Routine use of
dietary supplements is not recommended for the purposes of cancer control." The order of the sentences was also revised.
Physical Activity
SPA-1 General Principles
• Second bullet; Third arrow sub-bullet: Revised, "...major muscle groups at least two days per week on days that other exercises are
performed."
SPA-A Guidance for Resistance Training Recommendations

• New bullet added: Core and strength training is important to maintain balance and minimize fall risk.
• The following bullets and sub-bullets were revised
All major muscle groups (chest, shoulders, arms, back, abdomen core, and legs) should be incorporated into a resistance training
program.
Frequency: 2–3 times/wk; survivors should wait at least 48 hours between resistance training with adequate rest between sessions
For survivors who do not currently do resistance training: Start with one set of each exercise and progress up to 2–3 sets as tolerated wish
to start resistance training, refer to trained personnel or exercise specialist if available.
• The following bullets were removed
Multi-joint exercises are recommended over exercises focused on a single joint
Larger muscle groups (legs, back, and chest) should be worked before smaller muscle groups (arms and shoulders)
• Footnote e regarding trained personnel was added to this page.
Continued
® ® ®
UPDATES

Table of Contents
PREVENTIVE HEALTH
Physical Activity--continued SNWM-1 General Principles of Nutrition (continued)
SPA-B • Bullet revised: For patients desiring further recommendations for
• Examples of Physical Activity dietary guidelines, the USDA approximate food plate volumes (www.
Footnote b reference updated to U.S. Department of Health choosemyplate.gov) are:
and Human Services. Move Your Way. Washington, DC: U.S. • New sub-bullet added: Consider referral to a dietitian or nutritionist.
Department of Health and Human Services. https://health.gov/ • Sub-bullet revised: "The USDA approximate food plate volumes
moveyourway (www.choosemyplate.gov) are: Vegetables and fruits should
• Strategies to Increase Physical Activity comprise half the volume of food on the plate..."
Physician recommendation and/or fitness expert recommendation • Footnote a reference link updated: https://www.aicr.org/cancer-
Referral to trained personnel or exercise specialist if available prevention/food-facts/aicrs-new-american-plate/
SPA-C Considerations for Specific Populations SNWM-2 General Principles of Weight Management
• Ostomy users recommendations revised • This section was revised extensively. Many of the recommendations
New bullets added on this section were moved to page SNWM-4.
◊ Modify core exercises to minimize excess intra-abdominal
pressure and avoid Valsalva maneuvers, as ostomy survivors SNWM-4 Additional Nutrition and Weight Management Interventions
may be at risk for parastomal hernias. • New header "Goal" was added. The order of the "Goal" listings
◊ Use ostomy protector when engaging in contact sports or where were revised to Weight gain, Weight maintenance, and Weight Loss.
there is a risk of a trauma to the ostomy. Previously Weight gain was listed last and Weight loss was listed
◊ Discuss hydration strategies prior to, during, and after physical first.
activity in survivors with ileostomies, as dehydration is possible
given ostomy placement and output. Immunizations and Infections
Bullets removed • References were updated throughout the section.
◊ Use caution with contact sports and exercises that result in SIMIN-2
excessive intra-abdominal pressure • Risk Assessment and Screening; Risk factors for infections:
◊ Infection precautions are recommended Seventh bullet revised: Prior Hematopoietic cell transplantation
New reference added: Campbell KL, Winters-Stone KM, Wiskemann (HCT) cellular therapies. HCT listed as a separate sub-bullet.
J, et al. Exercise guidelines for cancer survivors: Consensus CAR T-cell therapy added under "Prior cellular therapies"
statement from international multidisciplinary roundtable. Med Sci • Interventions; Education on infection prevention practices: Proper
Sports Exerc 2019;51:2375-2390. hand hygiene added with corresponding new footnote j "For proper
hand hygiene see the Centers for Disease Control and Prevention
Nutrition and Weight Management "Clean Handwashing: Clean Hands Save Lives" campaign https://
SNWM-1 General Principles of Nutrition www.cdc.gov/handwashing/."
• Second bullet revised: "Assess eating and snacking habits,
including portion size, night grazing, snacking habits, frequency of SIMIN-3
eating out, timing of meals, and..." • Treatment; Fourth bullet: Revised, Human papillomavirus (HPV) in
• Third bullet, Third arrow sub-bullet revised: Limit refined sugars and previously unvaccinated females and males adults through 45 years
processed foods. of age
• Sub-bullet revised: Alcohol is high in calories, and leads to poorer • Footnote p: Reference updated
food choices, and is associated with elevated risk for several Continued
cancers. UPDATES

Table of Contents
PREVENTIVE HEALTH
SIMIN-B General Principles of Vaccines in Cancer Survivors 3 of 3 Vaccines Considered Safe for Cancer and Transplant Survivors
1 of 3 and Close Contacts
• Vaccination in Non-Tranplant Survivors: Last sub-bullet revised: • Recombinant viral antigens; Second bullet revised, Human
"Human papillomavirus (HPV) vaccine in adult survivors..." papillomavirus female and HPV male
2 of 3
• Heading change to: Vaccination in Hematopoietic Cell Transplant (HCT) SIMIN-C Principles of Influenza Vaccine(s)
Survivors Who Had Cellular Therapy (ie, HCT, CAR T-cell therapy) • References udpated
New bullet added: For infection concerns and recommended
prophylaxis for immune-targeted agents, see NCCN Guidelines for SIMIN-D Principles Of Zoster (Shingles) Vaccine Use In Cancer Or
Prevention and Treatment of Cancer-Related Infections. Transplant Survivors
• Human papillomavirus vaccine: Revised to, "Administration of 3 doses • Recombinant zoster vaccine listed as preferred.
of HPV vaccine 6–12 months after HCT for adult survivors through age
45 years.
LATE EFFECTS/LONG-TERM PSYCHOSOCIAL AND PHYSICAL PROBLEMS
Anthracycline-Induced Cardiac Toxicity SCARDIO-3
SCARDIO-1 • Treatment: Revised, "Address underlying risk factors (hypertension,
• Footnote 1: New reference added. lipids, cigarette/tobacco use..."
SCARDO-2 Anxiety, Depression, Trauma, and Distress

• Initial Clinical Assessment For Patients Who Have Received Previous SANXDE-1
Anthracycline Therapy • Second bullet revised: "Survivors of cancer and its treatment.."
The following bullets were moved up in the list:
◊ Review medications, alcohol use, and other substance use SANXDE-8
– Review oncologic history • Non-pharmacologic interventions; For adjustment disorder or distress
– Review total cumulative dose of anthracycline without safety risk, mania, or psychosis: The following bullets were
– Other systemic therapy and/or chest radiation therapy revised:
• Second column; Second bullet revised Cognitive behavioral therapy (CBT) (eg, mindfulness, behavioral
Consider two-dimensional echocardiogram (ECHO) with doppler flow activation, structured CBT groups, digital modalities)
study for survivors with one or more risk factors within 1 year after Consider referral to chaplain for spiritual support for religious
completion of anthracycline therapy for survivors with conflict, concerns about death and afterlife, guilt, grief, and meaning
◊ High cumulative anthracycline dose and purpose in life
◊ Low cumulative anthracycline dose and 1 or more heart failure risk Consider referral for couples, family, caregiver, or relationship
factors counseling/support
• New footnote f added: For survivors of certain cancer types, longer-
term cardiovascular surveillance may be needed. Please see the NCCN SANXDE-C Principles of Pharmacologic Interventions
Guidelines for Treatment of Cancer by Site for specific monitoring • Caveats; Fifth bullet; Use psychotropics with cytochrome P450
recommendations. interactions with caution in survivors taking tamoxifen: Duloxetine and
• Footnote removed: Trastuzumab, pertuzumab (other HER2-targeted clomipramine were added to the list.
therapy), VEGF signaling pathway (VSP) inhibitors, or taxanes in • Footnote a revised: Pure SSRIs, and in particular paroxetine, block
combination with anthracyclines. conversion of tamoxifen to active metabolites through CYP2D6 and
should be used with caution for women on tamoxifen. Continued
UPDATES

Table of Contents

Cognitive Function
• There were no updates for this version. (SCF-1) SMP-4 (Females)
• Vasomotor symptoms;Non-hormonal pharmacologic treatments;
Fatigue Sub-bullet revised: "Categories include low-dose antidepressants..."
• There were no updates for this version. (SFAT-1) • New footnote i added: Lower doses of antidepressants are often
effective if the intent is to treat hot flashes (See SMP-A).
Lymphedema • Second bullet in footnote j revised: "...however, randomized data
SLYMPH-A Survivor Lymphedema Education in breast cancer survivors show no benefit (www.ncbi.nlm.nih.gov/
• Third bullet; New sub-bullet added: Water exercise under pubmed/16782922). There is concern about potential liver toxicity
supervision may be an option to consider after assessing any with long-term use of black cohosh.
skin integrity and/or incision issues with corresponding footnote
reference 4, Lindquist H, Enblom A. Water exercise compared to SMP-5 (Females)
land exercise or standard care in female cancer survivors with • Vaginal dryness; Treatment
secondary lymphedema. Lymphology 2015;48:64-79. Non-hormonal treatments: Topical vitamin D and E were removed
New bullet added: For vaginal pain or discomfort see SFF-2.
Hormone-Related Symptoms • Footnote n is new: Survivors should be cautioned that some
SMP-1 Principles of Menopause Management in Female Survivors lubricants may be irritating to the area of application.
• Menopause • Footnote p is new: Although compounded testosterone vaginal
New bullets added: creams are often used, there is a lack of data showing efficacy or
◊ In non-cancer populations, primary ovarian insufficiency or safety in cancer survivors.
early menopause may be associated with specific menopause-
related health risks (see below). There are limited data in cancer SMP-A Non-Hormonal Pharmacologic Treatments and Dosing
survivors. • Footnote d revised: Pure SSRIs, and in particular paroxetine, block
◊ Survivors who have become amenorrheic and are sexually conversion of tamoxifen to active metabolites through CYP2D6 and
active should be counseled on the need for contraception to should be used with caution for women on tamoxifen.
prevent unintended pregnancy if they do not meet the definition
of menopause. SMP-B Principles of Menopausal Hormone Therapy Use in Survivors
Bullet revised: For Peri- or pre-menopausal female survivors (Females)
◊ For survivors who have become amenorrheic... • Second bullet; Sub-bullet revised: There is a lack of data supporting
• Menopause-related health risks: Cognitive change and Parkinson's claims that custom-compounded bioidentical hormones are a safer
disease were added. and more effective alternative to standard hormone therapies. In
• Treatment options for vasomotor symptoms; Hormonal therapies: fact, they may be harmful.
Sub-bullet revised, Custom-compounded bioidentical hormone
therapy (contraindicated in survivors of hormonally mediated
cancers; use with caution in those with increased genetic cancer
risk) (See SMP-B)
Continued
UPDATES

Table of Contents
PAIN
SPAIN-1 General Principles of Pain Management
• New bullet added: The panel acknowledges the legalization of medical marijuana for various conditions in multiple states. However, there are
presently not enough data to make any guideline recommendations regarding use in cancer survivors.
SPAIN-10 Post-radiation Pain

• First column; Third bullet revised: Radiation to a localized area of the body (ie, head and neck, breast) may cause a chronic pain syndrome in
that area.
• Treatment: New bullet added, Consider referral to pain management services, interventional specialist, physical therapy, physical medicine
and rehabilitation, orthopedic services, and/or palliative care for post-radiation pain including after stereotactic body RT (SBRT).
Sexual Function
SSF-2 Sexual Function (Female)
• Low or lack of desire, libido, or intimacy; Treatment: Revised, Discussion of available drugs (ie, androgens, bupropion, buspirone,
flibanserin, bremelanotide)
Sleep Disorders
• There were no updates for this version. (SSD-1)
Continued
UPDATES

Table of Contents
General Survivorship
Principles

Table of Contents
DEFINITION OF SURVIVORSHIP
• An individual is considered a cancer survivor from the time of diagnosis, during and immediately after treatment, and through the balance of
his or her life. Family members, friends, and caregivers are also affected by cancer.a
• These guidelines focus on the vast and persistent impact both the diagnosis and treatment of cancer have on the adult survivor. This
includes the potential impact on health, physical and mental states, health behaviors, professional and personal identity, sexuality, and
financial standing.
• These guidelines are applicable to survivors across the continuum of care, including those on endocrine therapy, with chronic cancers (eg,
metastatic disease), and long-term survivors.
STANDARDS FOR SURVIVORSHIP CAREb
Care of the cancer survivor should include:
1. Prevention of new and recurrent cancers and other late effects
2. Surveillance for cancer spread or recurrence, and screening for subsequent primary cancers (SURV-3)c
3. Assessment of late psychosocial, physical, and immunologic effects
4. Intervention for consequences of cancer and treatment
(eg, medical problems, symptoms, psychologic distress, financial and social concerns)
5. Coordination of care between primary care providers and specialists to ensure that all of the survivor's health needs are met
6. Planning for ongoing survivorship care:d
◊ Information on treatment received including all surgeries, radiation therapy, and systemic therapies
◊ Information regarding follow-up care, surveillance, and screening recommendations
◊ Information on post-treatment needs, including information regarding acute, late, and long-term treatment-related side effects and health
risks when possible (See NCCN Guidelines for Treatment of Cancer by Site)
◊ Delineation regarding roles of oncologists, primary care physicians (PCPs), and subspecialty care physicians in long-term care and the
timing of transfer of care if appropriate
◊ Healthy behavior recommendations (See HL-1)
◊ Periodic assessment of ongoing needs and identification of appropriate resources
aAdapted with permission from the National Coalition for Cancer Survivorship as shown in the National Cancer Institute’s Office of Cancer Survivorship Definitions web
page, available at https://cancercontrol.cancer.gov/ocs/statistics/index.html#definition-survivorship.
bFrom Hewitt M, Greenfield S, Stovall E. From Cancer Patient to Cancer Survivor: Lost in Transition. Committee on Cancer Survivorship: Improving Care and Quality of
Life, Institute of Medicine and National Research Council 2006. Available at: http://www.nap.edu/catalog/11468.html.
cSurveillance testing (eg, labwork, imaging, other studies) should be based on cancer diagnosis and individualized patient risk. A small excess risk of cancer has been
linked to frequent radiographic imaging. Surveillance testing should be performed as per NCCN Guidelines for Treatment of Cancer by Site. Additional labwork, imaging,
or other studies to evaluate for recurrence should be based on clinical presentation and judgment.
dCommission on Cancer: Optimal Resources for Cancer Care (2020 Standards): https://www.facs.org/-/media/files/quality-programs/cancer/coc/optimal_resources_for_
cancer_care_2020_standards.ashx.
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
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GENERAL PRINCIPLES OF THE SURVIVORSHIP GUIDELINES
• These guidelines are focused on options to maintain and enhance wellness in cancer survivors, including those who are enduring ongoing
treatment, those who have completed cancer treatment, and those in clinical remission.
(Also see the NCCN Guidelines for Supportive Care Table of Contents)
• These guidelines are designed to provide a framework for the general survivorship care and management of potential long-term and/or late
effects of cancer and its treatment that survivors may experience.
• The NCCN Guidelines for Survivorship should be used as a supplement to the follow-up recommendations within the disease-specific
guidelines. See the NCCN Guidelines for Treatment of Cancer by Site and NCCN Guidelines for Palliative Care for recommendations
regarding metastatic disease.
• These guidelines provide screening, evaluation, and treatment recommendations for common consequences of cancer and cancer
treatment, and are intended for health care professionals who work with survivors of adult-onset cancer in the post-treatment period,
including those in both the oncology and primary care practices.
• These guidelines, with the appropriate disease-specific guideline, provide a framework for the coordination of care between the survivor's
health care providers to insure that needs are appropriately addressed.
• The panel does not assume that all survivorship issues will be addressed at every visit. The panel recommends periodic screening
assessments and appropriate follow-up care as clinically indicated.
• Referral to other health care disciplines/providers or community resources may be used to address several indications or identified issues
with one intervention (eg, rehabilitation for fatigue, depression, and pain).
• For survivorship issues related to younger populations, also see the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology and
the Children's Oncology Group Long-Term Follow-up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers
(www.survivorshipguidelines.org).
• For survivors treated with immunotherapy, ongoing surveillance for immune-mediated toxicities is warranted. See NCCN Guidelines for
Management of Immunotherapy-Related Toxicities.

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SCREENING FOR SUBSEQUENT NEW PRIMARY CANCERS

• Subsequent new primary malignant neoplasms may occur in survivors years after treatment when the survivor's oncologist may no longer
be involved in the survivor's care.
• The overall cancer rate in survivors is higher than in the general population. This increased risk is due to genetic susceptibilities (eg,
hereditary cancer syndromes) and/or family history, shared etiologic exposures (eg, smoking, environmental exposures), and mutagenic
effects of cancer treatment.
• Treatment-related subsequent primary cancers vary with the type and intensity of anticancer treatment and are associated in particular with
radiation and specific chemotherapeutic agents.
• Screening for subsequent primary cancers should be a shared responsibility between primary and oncology care physicians
(See the NCCN Guidelines for Detection, Prevention, and Risk Reduction Table of Contents).
• Evidence suggests that excess lifetime radiation exposure from CT imaging may be associated with a mildly increased risk of developing a
radiation-associated cancer. Use of radiologic studies to screen for recurrent cancer should be based on diagnosis and evidence that early
detection of recurrence will improve cancer-related outcomes. Recommendations for surveillance imaging modality and frequency can be
found in the NCCN Guidelines for Treatment of Cancer by Site.
• Healthy lifestyle and behavioral counseling are important to reduce risk factors that may contribute to subsequent cancers (See HL-1).
• Periodic updating of family cancer history (when known) is recommended to reassess hereditary risk, as it should not be assumed that all
cancer survivors were assessed at diagnosis. Genetic testing guidelines and knowledge about hereditary cancer risk evolve over time and
new family diagnoses may occur making periodic assessment important.
• Genetic risk assessment is appropriate for all breast cancer survivors, all survivors of epithelial ovarian cancer, survivors of colorectal or
endometrial cancer diagnosed at age 50 or younger, high-grade prostate cancer, or pancreatic cancer. Many other survivors of rare cancers,
cancers diagnosed at young ages, multiple primary cancers, or those with one or more relatives with the same or related cancers are
also candidates for risk assessment per guidelines from NCCN and other expert groups. Genetic testing is recommended for appropriate
survivors based on results of the risk assessment.
• Referral to genetic risk assessment and/or testing should be considered for appropriate candidates when available to identify those with
an increased risk for subsequent malignancies. Genetic testing may also provide opportunities to identify and reduce risks in relatives of
cancer survivors.
• Criteria for genetic risk assessment and testing, and for management of patients with known germline mutations linked to an increased risk
for cancer can be found in the following NCCN Guidelines:
NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic
NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal
NCCN Guidelines for Gastric Cancer
NCCN Guidelines for Neuroendocrine and Adrenal Tumors
NCCN Guidelines for Thyroid Carcinoma
NCCN Guidelines for Prostate Cancer
NCCN Guidelines for Cutaneous Melanoma

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ASSESSMENT BY HEALTH CARE PROVIDER (ONCOLOGY OR PRIMARY CARE) AT REGULAR INTERVALS
• A periodic assessment at least annually is recommended for all survivors to determine any needs and necessary interventions. For sample
assessment, see SURV-A.e
• Shared coordinated care between the oncology, primary care, and subspecialty care providers is encouraged. Depending on the cancer type
and stage of disease, transition of care to a PCP may be done when deemed clinically appropriate with referral back to oncologic care as
needed.
• Care providers are also encouraged to assess the following at regular intervals:
1. Current disease status
2. Functional/performance status
3. Medication use (including over-the-counter [OTC] medications and supplements)
4. Comorbidities
5. Prior cancer treatment history and modalities used
6. Family history
7. Psychosocial factors
8. Assess weight and health behaviors that can modify cancer and comorbidity risk (including tobacco/alcohol use)
9. See NCCN Guidelines for Treatment of Cancer by Site for disease-specific recommendations for surveillance/follow-up
eThis is a sample assessment tool. While this instrument has not yet been piloted or validated, the answers can be used to guide providers to topics within the
guidelines that require more in-depth assessment. Validation of the best way to assess survivorship issues is ongoing.

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SURVIVORSHIP ASSESSMENT (Patient Version)

Please answer the following questions:
Survivorship Survivorship Care Survey
Concerns
Cardiac Toxicity 1. Do you have shortness of breath or chest pain after physical activities (eg, climbing stairs) or exercise? Yes/No
2. Do you have shortness of breath when lying flat, wake up at night needing to get air, or have persistent leg swelling? Yes/No
Anxiety, 3. In the past two weeks, have you been bothered more than half the days by little interest or pleasure in doing things? Yes/No
Depression, 4. In the past two weeks, have you been bothered more than half the days by feeling down, depressed, or hopeless? Yes/No
Trauma, and 5. Has stress, worry, or being nervous, tense, or irritable interfered with your life? Yes/No
Distress
Cognitive 6. Do you have difficulties with multitasking or paying attention? Yes/No
Function 7. Do you have difficulties with remembering things? Yes/No
8. Does your thinking seem slow? Yes/No
Fatigue 9. Do you feel persistent fatigue despite a good night's sleep? Yes/No
10. Does fatigue interfere with your usual activities? Yes/No
11. How would you rate your fatigue on a scale of 0 (none) to 10 (extreme) over the past week? 0–10
Lymphedema 12. Since your cancer treatment, have you had any swelling, fatigue, heaviness, or fullness on the same side as your treatment that has not gone away?
Yes/No
Hormone- 13. Have you been bothered by hot flashes/night sweats? Yes/No
Related 14. Have you been bothered by other hormone-related symptoms (ex, vaginal dryness, incontinence)? Yes/No
Symptoms
Pain 15. Are you having any pain? Yes/No
16. How would you rate your pain on a scale of 0 (none) to 10 (extreme) over the past month? 0–10
Sexual Function 17. Do you have any concerns regarding your sexual function, sexual activity, sexual relationships, or sex life? Yes/No
18. Are these concerns causing you distress? Yes/No
Sleep Disorder 19. Are you having problems falling asleep, staying asleep, or waking up too early? Yes/No
20. Are you experiencing excessive sleepiness (ie, sleepiness or falling asleep in inappropriate situations or sleeping more during a
24-hour period than in the past)? Yes/No
21. Have you been told that you snore frequently or that you stop breathing during sleep? Yes/No
Healthy Lifestyle 22. Do you engage in regular physical activity or exercise, such as brisk walking, jogging, weight/resistance training, bicycling, swimming, etc.? Yes/No
► 22a. If you answered “Yes,” how often?
23. Excluding white potatoes, do you eat at least 2½ cups of fruits and/or vegetables each day? Yes/No
24. Do you have concerns about your weight? Yes/No
25. Do you take vitamins or other supplements? Yes/No
Immunizations 26. Have you received your flu vaccine this flu season? Yes/No
and Infections 27. Are you up to date on your vaccines? Yes/No/Don't know

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SURVIVORSHIP ASSESSMENTa
(Provider Key)
Based on the survivor's answers to the assessment questions, refer to the detailed recommendations indicated below:
Survivorship Concerns Survivorship Care Survey Provider Key
Cardiac Toxicity Questions 1–2 If YES to any question, refer to SCARDIO-1
Anxiety, Depression, and Distress Questions 3–5 If YES to any question, refer to SANXDE-1
Cognitive Function Questions 6–8 If YES to any question, refer to SCF-1
Fatigue Questions 9–11 If YES to either question 9 or 10,

or a rating of >3 to question 11,
refer to SFAT-1
Lymphedema Questions 12 If YES to question 12, refer to SLYMPH-1
Hormone-Related Symptoms Questions 13–14 If YES to any question, refer to SMP-1
Pain Questions 15–16 If YES to question 15

and a rating of >4 to question 16,
refer to SPAIN-1
Sexual Function Questions 17–18 If YES to any question, refer to SSF-1
Sleep Disorder Questions 19–21 If YES to any question, refer to SSD-1
Healthy Lifestyle Questions 22–25 If NO to question 22 or 23, or YES to question 24, OR if

question 22a is less than 3 times per week, OR if BMI not
in the healthy range, refer to HL-1
If YES to question 25, refer SSUP-1
Immunizations and Infections Questions 26–27 If NO to question 26,

or NO or DON'T KNOW to question 27,
refer to SIMIN-1
aThis is a sample assessment tool. While this instrument has not yet been piloted or validated, the answers can be used to guide providers to topics within the
guidelines that require more in-depth assessment. Validation of the best way to assess survivorship issues is ongoing.

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SURVIVORSHIP RESOURCES FOR HEALTH CARE PROFESSIONALS AND PATIENTSa

General Online Information
National Coalition for Cancer Survivorship (NCCS) http://www.canceradvocacy.org/
American Association for Cancer Research (AACR) http://www.aacr.org
American Cancer Society (ACS) http://www.cancer.org/index
• Survivorship information http://www.cancer.org/treatment/survivorshipduringandaftertreatment/index
• Cancer Survivors Network http://csn.cancer.org/
• National Cancer Survivorship Resource Center http://www.cancer.org/SurvivorshipCenter
• Physical side effects information, including sexual function http://www.cancer.org/treatment/treatmentsandsideeffects/physicalsideeffects/index
American Institute for Cancer Research (AICR): Survivorship information http://www.aicr.org/patients-survivors/
• Survivorship information
• Nutrition, physical activity, weight management
American Society of Clinical Oncology (ASCO) http://www.cancer.net/survivorship
• Survivorship information for patients https://www.asco.org/practice-policy/cancer-care-initiatives/prevention-survivorship/
• Tools and resources for oncology providers survivorship/survivorship-compendium
Cancer Care: Free, professional support services for anyone affected by cancer www.cancercare.org
Centers for Disease Control and Prevention: Survivorship information http://www.cdc.gov/cancer/survivorship/index.htm
Leukemia & Lymphoma Society: Survivorship information http://www.lls.org/diseaseinformation/managingyourcancer/survivorship/
LIVESTRONG http://www.livestrong.org/
National Cancer Institute: Cancer Survivorship Research http://survivorship.cancer.gov
• Springboard Beyond Cancer, Facing Forward series, designed to educate cancer https://survivorship.cancer.gov/springboard
survivors, family members, and health care providers about the challenges associated http://cancercontrol.cancer.gov/ocs/resources/ffseries.html
with life after cancer treatment
National Comprehensive Cancer Network (NCCN) http://www.nccn.org/index.asp
• Life After Cancer: Patient and Caregiver Resources and Information http://www.nccn.org/patients/resources/life_after_cancer/
MedlinePlus: Current accurate information by cancer site http://www.nlm.nih.gov/medlineplus/cancers.html
Oncology Nursing Society: Putting Evidence Into Practice https://www.ons.org/explore-entrance
Help Lines
American Cancer Society 1.800.227.2345 http://www.cancer.org
American Psychosocial Oncology Society 1.866.276.7443 http://apos-society.org/
Cancer Support Community 1.888.793.9355 http://www.cancersupportcommunity.org/
LIVESTRONG SurvivorCare 1.855.220.7777
National Cancer Institute’s Cancer Information Service 1.800.4.CANCER
National Suicide Prevention Lifeline 1-800-273-TALK http://suicidepreventionlifeline.org
aThere are many smart phone/tablet/mobile device apps, web-based programs, DVDs, and TV programs available to help survivors with various aspects of health care and wellness.
Continued
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Other Survivorship Guidelines
Children’s Oncology Group: Long-Term Follow-Up Guidelines for Survivors of Childhood, http://www.survivorshipguidelines.org/
Adolescent, and Young Adult Cancers
Survivorship Care Planning
ASCO Cancer Treatment Summaries http://www.cancer.net/survivorship/follow-care-after-cancer-treatment/asco-cancer-
treatment-and-survivorship-care-plans
Integrative Therapies
Memorial Sloan Kettering Cancer Center's Herbs website https://www.mskcc.org/cancer-care/treatments/symptom-management/integrative-medicine/
herbs
National Center for Complementary and Integrative Resources for Health Care Providers https://nccih.nih.gov/health/providers
Legal and Employment Issues
Cancer and Careers: Patient information about working and dealing with cancer http://www.cancerandcareers.org/en
National Coalition for Cancer Survivorship (NCCS) Employment Rights, http://www.canceradvocacy.org/resources/employment-rights/
“Working It Out” Publication
National Coalition for Cancer Survivorship (NCCS) “What Cancer Survivors Need To Know http://www.canceradvocacy.org/resources/health-insurance/
About Health Insurance” Publication
ACS: Understanding Health Insurance https://www.cancer.org/treatment/finding-and-paying-for-treatment/understanding-health-
insurance.html
Information About LGBTQ Individuals with Cancer
CDC Lesbian, Gay, Bisexual, and Transgender Health https://www.cdc.gov/lgbthealth/index.htm
National LGBT Cancer Network https://cancer-network.org/
Menopause and Sexual Health
The North American Menopause Society http://www.menopause.org
American College of Obstetricians and Gynecologists (ACOG) https://www.acog.org/
International Society for the Study of Women's Sexual Health (ISSWSH) https://www.isswsh.org/
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Physical Activity
American Cancer Society http://onlinelibrary.wiley.com/doi/10.3322/caac.21146/pdf
• Nutrition and Physical Activity Guidelines for Cancer Survivors, http://www.cancer.org/treatment/survivorshipduringandaftertreatment/stayingactive/
Patient Page physical-activity-and-the-cancer-patient
• “Physical Activity and the Cancer Patient” guide
American College of Sports Medicine: ACSM ProFinder: Search for Certified Professionals https://www.acsm.org/get-stay-certified/find-a-pro
Cancer Supportive and Survivorship Care: Exercise: A Cancer Survivor’s Tool For http://www.cancersupportivecare.com/whyexercise.html
Wellness
LIVESTRONG at the YMCA http://www.livestrong.org/YMCA
SilverSneakers: A program that helps older adults live healthy, active lifestyles https://www.silversneakers.com/
Nutrition and Weight Management
ASCO Obesity and Cancer Toolkit https://www.asco.org/practice-policy/cancer-care-initiatives/prevention-survivorship/obesity-
cancer
Cancer Nutrition Consortium: Nutritional Guidance & Support https://www.cancernutrition.org/
LIVESTRONG MyPlate Calorie Tracker http://www.livestrong.com/myplate
National Heart, Lung, and Blood Institute
• Guideline for the Management of Overweight and Obesity in Adults http://www.nhlbi.nih.gov/health-pro/guidelines/in-develop/obesity-evidence-review
• 3 Steps to Initiate Discussion About Weight Management With Your Patients http://www.nhlbi.nih.gov/health/prof/heart/obesity/aim_kit/steps.pdf
National Institute of Diabetes and Digestive Kidney Diseases https://www.niddk.nih.gov/health-information/health-topics/weight-control/body-weight-
Body Weight Planner planner/Pages/bwp.aspx/Pages/default.aspx
New American Plate http://www.aicr.org/new-american-plate
Oncology Nutrition Dietetic Practice Group of the Academy of Nutrition and Dietetics http://www.oncologynutrition.org/
Cardiovascular Health
American Heart Association/American Stroke Association Tools https://millionhearts.hhs.gov/tools-protocols/tools.html
CardioOnc.org (database of cancer drugs and cardiac toxicities) http://cardioonc.org/providers/
Oral and Dental Health
National Institute of Dental and Craniofacial Research: Oral Complications of Cancer http://www.nidcr.nih.gov/oralhealth/Topics/CancerTreatment/OralComplicationsCancerOral.
Treatment htm
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Sleep Disorders
National Cancer Institute Sleep Disorders (PDQ®)–Health Professional Version https://www.cancer.gov/about-cancer/treatment/side-effects/sleep-disorders-hp-pdq
Smoking Cessation
American Cancer Society: Smoking cessation support http://www.cancer.org/healthy/stayawayfromtobacco/index
ASCO: Tobacco Cessation and Control Resources https://www.asco.org/practice-policy/cancer-care-initiatives/prevention-survivorship/
tobacco-cessation-control
North American Quitline Consortium http://map.naquitline.org/
U.S. Federal Government: Smoking cessation support http://www.smokefree.gov/
Suicide Prevention and Other Psychosocial Issues
Veterans Affairs/Department of Defense Practice Guidelines: https://www.healthquality.va.gov/guidelines/MH/srb/
Assessment and Management of Patients at Risk for Suicide VASuicidePreventionPocketGuidePRINT508FINAL.pdf
NCCN Guidelines for Patients: Distress https://www.nccn.org/patients/guidelines/distress/index.html
Anxiety and Depression Association of America https://adaa.org/
https://adaa.org/finding-help/mobile-apps

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Preventive Health

Table of Contents
Survivorship Healthy Lifestyles
Survivorship: Discussion
GENERAL PRINCIPLES OF HEALTHY LIFESTYLES

• Healthy lifestyle habits have been associated with improved overall health and quality of life. For some cancers, a healthy lifestyle has
been associated with a reduced risk of recurrence and death.
• All survivors should be encouraged to achieve and maintain a healthy lifestyle. At a minimum all survivors should be encouraged to:
Achieve and maintain a healthy body weight throughout life (SNWM-2).
Engage in physical activity (eg, exercise, taking the stairs, parking in the back of parking lot) daily (SPA-1).
Maintain a healthy diet high in vegetables, fruits, and whole grains and low in excess sugars, fried foods, and red and processed meat
(SNWM-1).
Minimize alcohol intake (SNWM-1).
Avoid use or stop using cigarette/tobacco products. (See NCCN Guidelines for Smoking Cessation)
Practice sun safety.
◊ Utilize a sunscreen with an SPF of at least 30 that protects against UVA and UVB rays and is water resistant.
◊ Apply sunscreen generously and reapply every 2 hours or after swimming/excessive sweating.
◊ Consider using physical barriers whenever possible (ie, hats, shirts with sleeves, avoiding direct sun during peak hours).
◊ Avoid tanning beds.
Ensure adequate amount of sleep (SSD-1).
Follow up with PCP regularly.
◊ Adhere to age-appropriate and treatment-associated health screening, preventive measures (SIMIN-1), and cancer screening
recommendations (See NCCN Guidelines for Detection, Prevention, & Risk Reduction).
• Obtain nutrients from food sources rather than relying on dietary supplements. Routine use of dietary supplements is not recommended
for the purposes of cancer control. (SSUP-1)
• Set incremental goals for diet, physical activity, and weight management.
• Clinicians should assess individual and community-level barriers to meeting the healthy lifestyle recommendations and support patients
in developing strategies to overcome challenges.

HL-1

Table of Contents
Survivorship Physical Activity
GENERAL PRINCIPLES OF PHYSICAL ACTIVITY

• Physical activity and exercise recommendations should be tailored to individual survivor’s abilities and preferences
• Physical activity for cancer survivors:a
Overall volume of weekly activity should be at least 150–300 minutes of moderate-intensityb activity or 75 minutes of vigorous-intensityb
activity or equivalent combination spread out over the course of the week.
Two to three sessions per week of strength/resistance training that include major muscle groups (See SPA-A)
Stretch major muscle groups at least two days per week on days that other exercises are performed
• Engage in general physical activity daily (eg, taking the stairs, parking in the back of parking lot)
Physical activity includes exercise, daily routine activities, and recreational activities
• Avoid prolonged sedentary behavior (eg, sitting for long periods)
aRock CL, Doyle C, Demark-Wahnefried W, et al. Nutrition and physical activity guidelines for cancer survivors. CA Cancer J Clin 2012;62:243-274.
Available at: http://onlinelibrary.wiley.com/doi/10.3322/caac.21142/full. Schmitz KH, Courneya KS, Matthews C, et al. American College of Sports Medicine roundtable
on exercise guidelines for cancer survivors. Medicine & Science in Sports & Exercise 2010;42:1409-1426.
Available at: http://journals.lww.com/acsm-msse/Fulltext/2010/07000/American_College_of_Sports_Medicine_Roundtable_on.23.aspx.
bLight physical activity: No noticeable change in breathing pattern; Moderate exercise: Can talk, but not sing; Vigorous exercise: Can say a few words without stopping
to catch a breath (See Examples of Physical Activity [SPA-B]).

SPA-1

Table of Contents
PHYSICAL ACTIVITY ASSESSMENT
Focused clinical evaluation

Assessment of
• Weight/BMI
comorbidities and treatment
• Blood pressure
effects as appropriate:
• Functional status
• Cardiovascular
• Assess baseline level of activity prior to
disease (including
diagnosis and current level of activityc
cardiomyopathy)
• Barriers to physical activity as assessed
• Pulmonary disease
by survivor
• Arthritis/musculoskeletal
Environmental
Ask about prior issues
(home, gym access, outdoor space)
and current • Lymphedema
Financial
participation in • Peripheral neuropathy Determine risk level
Physical limits
physical activity • Bone health/bone strength for exercise-induced
Time/competing demands
and assess level (including presence of adverse events
Social support
of current physical bone metastases) (See SPA-3)
Stress
activity at regular • Incontinence or bowel/
• Review of systems
intervals bladder symptoms
• Disease status
• Presence of stoma or
• Nutritional status
ostomy
Assessment of treatable
• Fall risk assessment
contributing factors
• Need for assistive devices
• Pain
(cane, walker, brace, etc.)
• Fatigue
• History or presence of
• Emotional distress
anemia/thrombocytopenia
• Nutritional deficits/imbalance
• Steroid myopathy
• Medications/side effects
cAsk patient about duration, intensity, and frequency of activity. For example, see Godin G and Shepard RJ. Godin Leisure-Time Exercise questionnaire. Medicine and
Science in Sports and Exercise 1997; 29 June Supplement: S36-S38.
(https://journals.lww.com/acsm-msse/Fulltext/1997/06001/Godin_Leisure_Time_Exercise_Questionnaire.9.aspx)

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Table of Contents
RISK ASSESSMENT FOR PHYSICAL ACTIVITY-INDUCED ADVERSE EVENTS
General recommendationsd for physical

No significant comorbidities
activity for cancer survivors
• General recommendationsd for cancer

• Peripheral neuropathy Implementation of
survivors with modifications based on
• Arthritis/musculoskeletal issues physical activity
assessment
(See SPAIN-6) recommendations
• Consider medical evaluation prior to
• Poor bone health (See SPA-4)
initiation of exercise program
• Lymphedema (See SLYMPH-B)
• Consider referral to trained personnele
• History of lung surgery or major abdominal Considerations
surgery for specific
• Ostomy populations
• Cardiopulmonary comorbidities (See SPA-C)
(ie, chronic obstructive pulmonary
disease [COPD], congestive heart failure • Medical evaluation and clearance
[CHF], coronary artery disease [CAD], by physician prior to initiation of
cardiomyopathy) exercise program
(See SCARDIO-1) • Refer to trained personnele
• Severe fatigue (See SFAT-1)
• Ataxia
• Severe nutritional deficiencies (See SNWM-3)
• Worsening/changing physical condition
(ie, lymphedema exacerbation)
dSee General Principles of Physical Activity (SPA-1).

eTrained personnel can include physical and occupational therapists, certified exercise professionals, and rehabilitation specialists. Specialized training in working with
survivors is available for both physical therapists and exercise professionals (American College of Sports Medicine [ACSM] [http://www.acsm.org/get-stay-certified] and
American Physical Therapy Association [APTA] Oncology section [http://oncologypt.org]).

SPA-3

Table of Contents
IMPLEMENTATION OF RECOMMENDATIONSf
• Periodic reassessment, positive
reinforcement with review of benefits of
exercise, and encouragement to maintain
Meeting Guideline activity level i
recommendationsd,g • Discuss and review possible side effects
of and/or barriers to exercise (eg, pain,
access)
Current or prior
exercise
behavior:
• Frequency If toleratingg
• Intensity
• Type
• Time • Evaluate and address barriers
• Develop incremental short- Progression:
and long-term goals regarding If
• Incremental increases in time spent in
physical activity participation. tolerating i
physical activity or in intensity of activity
• Suggested initial prescription:
Not meeting Guideline Frequency: 1–3 days/wk
recommendationsd,h Intensity: Light to moderate i
(See SPA-3) Type: Aerobic activity
(ie, walking) and/or resistance
prescriptionj If not
Time goal: 20 min/session tolerating Consider referral to appropriate
or not trained personnele
progressing
dSee General Principles of Physical Activity (SPA-1).
eTrained personnel can include physical and occupational therapists, certified
exercise professionals, and rehabilitation specialists. Specialized training in working
with survivors is available for both physical therapists and exercise professionals gIf tolerating minimum guideline recommendations, consider encouragement of
(American College of Sports Medicine [ACSM] [http://www.acsm.org/get-stay- variation within exercise program or physical activities.
certified] and American Physical Therapy Association [APTA] Oncology section hPatients with comorbidities may need additional evaluation before doing more
[http://oncologypt.org]). rigorous activity.
fReproduced and adapted with permission from Jones LW, Eves ND, Peppercorn iSee Examples of Physical Activity and Strategies to Increase Physical Activity
J. Pre-exercise screening and prescription guidelines for cancer patients. Lancet (SPA-B).
Oncol 2010;11:914-916. jSee Guidance for Resistance Training Recommendations (SPA-A).

SPA-4

Table of Contents
GUIDANCE FOR RESISTANCE TRAINING RECOMMENDATIONS

• Health benefits of resistance training include improvement in muscle strength and endurance, improvements in functional status, and
maintenance/improvement in bone density.
• Core and strength training is important to maintain balance and minimize fall risk.
• All major muscle groups (chest, shoulders, arms, back, core, and legs) should be incorporated into a resistance training program.
• Resistance training prescription
Frequency: 2–3 times/wk with adequate rest between sessions
Intensity: 2–3 sets of 10–15 repetitions per set; consider increasing weight amount as tolerated when 3 sets of 10–15 repetitions becomes
easy
Rest: 2- to 3-minute rest period between sets and exercises
For survivors who wish to start resistance training, refer to trained personnel or exercise specialist if available.a
• Utilize weight amount that would allow for performance of 10–15 repetitions.
• For survivors at risk for or with lymphedema, See SLYMPH-B.
aTrained personnel can include physical and occupational therapists, certified exercise professionals, and rehabilitation specialists. Specialized training in
working with survivors is available for both physical therapists and exercise professionals (American College of Sports Medicine [ACSM] [http://www.acsm.org/
get-stay-certified] and American Physical Therapy Association [APTA] Oncology section [http://oncologypt.org]).

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EXAMPLES OF PHYSICAL ACTIVITY

Light Exercisea Moderate Exerciseb Vigorous Exerciseb
(No noticeable change in breathing pattern) (Can talk, but not sing) (Can say a few words without stopping to
• Leisurely biking at 5 miles/hour or less • Ballroom/line dancing catch a breath)
• Activity-promoting video game • Biking on level ground or with few hills • Aerobic/Fast dancing
• Light housework (light sweeping, dusting) • General gardening • Biking faster than 10 miles/hour
• Bowling • Baseball, softball, volleyball • Heavy gardening
• Playing catch • Doubles tennis • Hiking uphill
• Slow walking • Using a manual wheelchair • Jumping rope
• Child care • Brisk walking • Martial arts
• Yoga • Water aerobics • Race walking, jogging, running
• Tai chi • Yoga • Running sports (basketball, hockey, soccer)
• Pilates • Swimming (fast pace or laps)
• Singles tennis
• Stair climbing
• High-intensity yoga
STRATEGIES TO INCREASE PHYSICAL ACTIVITY
• Physician recommendation
• Referral to trained personnel or exercise specialist if available
• Supervised exercise program or classes
• Telephone counseling
• Motivational interviewingc
• Evaluate readiness to change, importance of change, self-efficacy
• Cancer survivor-specific print materials (See SURV-B 2 of 2)
• Set short- and long-term goals
• Consider use of pedometer or wearable fitness tracker to monitor activity goals
(eg, obtain 10,000 steps per day)
• Encourage social support (exercise buddy, group)
aFrom the National Heart, Lung, and Blood Institute (http://www.nhlbi.nih.gov/health/public/heart/obesity/lose_wt/phy_act.htm) and the Compendium of Physical
Activities (https://sites.google.com/site/compendiumofphysicalactivities).
bReproduced and adapted from U.S. Department of Health and Human Services. Move Your Way. Washington, DC: U.S. Department of Health and Human Services.
https://health.gov/moveyourway. Accessed March 16, 2020.
cConsider referral to trained personnel.

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CONSIDERATIONS FOR SPECIFIC POPULATIONSa

• Established lymphedema:
For workup and treatment of established lymphedema (See SLYMPH-3)
For considerations regarding physical activity in survivors with established lymphedema (See SLYMPH-B)
• Ostomy users:1
Empty ostomy bag before engaging in exercise
Weight lifting/resistance exercises should start with low resistance and progress slowly under the guidance of trained exercise
professionalsb
Modify core exercises to minimize excess intra-abdominal pressure and avoid Valsalva maneuvers, as ostomy survivors may be at risk for
parastomal hernias.
Use ostomy protector when engaging in contact sports or where there is a risk of a trauma to the ostomy.
Discuss hydration strategies prior to, during, and after physical activity in survivors with ileostomies, as dehydration is possible given
ostomy placement and output.
• Peripheral neuropathy:
Stability, balance, and gait should be assessed before engaging in exercise; consider balance training as indicated
Consider alternative aerobic exercise (stationary biking, water aerobics) rather than walking if neuropathy affects stability
Resistance training recommendations:
◊ Monitor discomfort in hands when using hand-held weights
◊ Consider using dumbbells with soft/rubber coating, and/or wear padded gloves (eg, cycling gloves)
◊ Consider resistance training machines
Footnotes
aWhen possible, survivors in these populations should initiate an exercise program under supervision by trained personnel.
bTrained personnel can include physical and occupational therapists, certified exercise professionals, and rehabilitation specialists. Specialized training in working with
survivors is available for both physical therapists and exercise professionals (American College of Sports Medicine [ACSM] [http://www.acsm.org/get-stay-certified] or
References
1Campbell KL, Winters-Stone KM, Wiskemann J, et al. Exercise guidelines for cancer survivors: Consensus statement from international multidisciplinary roundtable.
Med Sci Sports Exerc 2019;51:2375-2390.

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Survivorship Nutrition and Weight Management
GENERAL PRINCIPLES OF NUTRITION

• Assess dietary pattern for daily intake of fruits, vegetables, and unrefined grains, as well as red and processed meats, alcohol, and
processed foods or beverages with added fats and/or sugars.
• Assess eating and snacking habits, including portion size, frequency of eating out, timing of meals, and use of added fats and/or sugars to
foods or beverages.
• All survivors should be encouraged to:
Make informed choices about food to ensure variety and adequate nutrient intake.
Limit red meat intake to <18 oz per week and avoid processed meat.
Limit refined sugars and processed foods.
Eat a diet that is at least 50% plant-based, with the majority of food being vegetables, fruit, and whole grains.a,b
Track calorie intake.
◊ Self-monitoring of caloric intake has been shown to be an effective strategy for weight management.
Minimize alcohol intake.
◊ Limit intake to no more than one drink per day for a woman and two drinks per day for a man.c,d
◊ Alcohol is high in calories, leads to poorer food choices, and is associated with elevated risk for several cancers.
• For patients desiring further recommendations for dietary guidelines
Consider referral to a dietitian or nutritionist.
The USDA approximate food plate volumes (www.choosemyplate.gov) are:
◊ Vegetables and fruits should comprise half the volume of food on the plate
◊ Vegetables: 30% of plate; fruits 20% of plate
◊ Whole grains: 30% of plate
◊ Protein: 20% of plate
• Recommended sources of dietary components:
Fat: plant sources such as olive or canola oil, avocados, seeds and nuts, and fatty fishe
Carbohydrates: fruits, vegetables, whole grains, and legumes
Protein: poultry, fish, legumes, low-fat dairy foods, and nuts
• Currently there is no consensus either refuting or supporting the role of soy foods in cancer control. Thus, moderate consumption
(3 or fewer servings per day) of soy foods is considered prudent.
aRecommendation for healthy food portion sizes can be found on the American Institute of Cancer Research (AICR) New American Plate website
(https://www.aicr.org/cancer-prevention/food-facts/aicrs-new-american-plate/) as well as the USDA “Choose My Plate” website www.choosemyplate.gov.
bEncourage the use of healthy recipes from resources such as the American Cancer Society’s “Find Healthy Recipes” website:
http://www.cancer.org/healthy/eathealthygetactive/eathealthy/findhealthyrecipes/maindishes/index.
cRock CL, Doyle C, Demark-Wahnefried W, et al. Nutrition and physical activity guidelines for cancer survivors. CA Cancer J Clin 2012;62:242-274.
Available at: http://onlinelibrary.wiley.com/doi/10.3322/caac.21142/full.
dThere are some cancers for which survivors should abstain from alcohol. These include liver, esophageal, kidney, and head and neck cancers.
eThese foods are high in calories and should be limited if overweight or obesity is an issue.

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GENERAL PRINCIPLES OF WEIGHT MANAGEMENT

• All survivors should be encouraged to achieve and maintain a normal body mass index (BMI) and strive for metabolic health.
Weight gain should be a priority for underweight survivors. (See SNWM-4)
Weight loss should be a priority for overweight/obese survivors.
◊ Weight gain after cancer diagnosis and treatment is common and can exacerbate risk for functional decline, comorbidity, and possibly
cancer recurrence or death, and can reduce quality of life.
Weight maintenance should be a priority for normal weight survivors.
• In conjunction with primary care, survivors should be assessed for metabolic health and body composition independently of BMI.
• Providers should discuss strategies for weight management.
◊ Practice portion control.
◊ Make informed food choices through routine evaluation of food labels.
◊ Incorporate physical activity, particularly strength training, to assure optimal lean body mass (SPA-1).
◊ Track weight, diet, calories, and physical activity routines (eg, journaling, mobile-phone apps).
• Referrals to registered dietitians, especially those who are Certified Specialists in Oncology Nutrition (CSO) and members of the Oncology
Nutrition Dietetic Practice Group of the Academy of Nutrition and Dietetics, should be considered.f
• There is no current evidence to support the use of weight loss supplements in cancer survivors.
fMany hospitals employ CSOs and those in private practice can be accessed via the Academy of Nutrition and Dietetics locator at www.eatright.org.

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NUTRITION AND WEIGHT MANAGEMENT INTERVENTIONS

ASSESSMENTg Assess treatment effects and
medical issues:
• Effects of treatment
GI dysmotility
Swallowing issues/
Clinical evaluation: dysphagia
• Assess current dietary Dysgeusia/change in taste
and physical activity Oropharyngeal anatomic
habits and ask about: changes
Daily food intake and Bowel dysfunction • Discuss “General
eating habits Digestive enzyme Principles of
• Evaluate Physical activity habits insufficiency Nutrition”
weight status Willingness to address GI tract (See SNWM-1)
based on BMI weight (if necessary) and reconstruction/ • Discuss “General Additional Nutrition and
criteriah past strategies used to anastomoses Principles of Weight Weight Management
• Evaluate changej • Comorbidities: Management” Interventions (See SNWM-4)
involuntary Barriers to nutrition and Cardiovascular disease (See SNWM-2)
weight weight management: Diabetes • Discuss “General
changei ◊ Access to healthful, Renal disease Principles of
nutrient-dense foods Liver disease Physical Activity”
◊ Financial and Mood disorders (See SPA-1)
socioeconomic issues (eg, anxiety and
◊ Time depression)
Appetite and changes in Thyroid dysfunction
eating patterns GI disease
• Medication use
• Dental health
• Supplement use
• Psychosocial distress and
fear of recurrence
gCoordination with primary care physicians and other involved providers is recommended.
hThe following BMI calculator from the Centers for Disease Control and Prevention may be used:
http://www.cdc.gov/healthyweight/assessing/bmi/adult_bmi/english_bmi_calculator/bmi_calculator.html.
BMI is calculated using the following formula: weight in pounds (lbs) X 703 / height in inches squared. The weight categories are as follows:
Underweight (BMI <18.5 kg/m2), Normal weight (BMI 18.5–24.9 kg/m2), Overweight (BMI 25–29.9 kg/m2), Obese (BMI ≥30 kg/m2).
iConsider workup for disease recurrence in the setting of cachexia or signifcant involuntary weight loss/gain >5% within 3 months.
jFor additional resources see the ASCO Toolkit on Obesity and Cancer: https://www.asco.org/practice-policy/cancer-care-initiatives/prevention-survivorship/obesity-cancer
and the LIVESTRONG My Plate Calorie Tracker: http://www.livestrong.com/myplate.

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GOAL ADDITIONAL NUTRITION AND WEIGHT MANAGEMENT INTERVENTIONSg,j

• Discuss increasing frequency of feeding
• Discuss avoiding fluid intake with meals
• Encourage foods that are both high in calories and nutrient-dense (eg, avocados, nuts)
• Manage contributing treatment effects and risk factors as clinically indicated
Dental health and risk factors for poor oral intake
Swallowing disorder, taste/smell disorders, and GI motility as appropriate
Weight gaink Offer smoking cessation assistance as appropriate
(See NCCN Guidelines for Smoking Cessation)
Contributing psychosocial factors (See SANXDE-1)
Barriers to food access and preparation such as living too far from grocery store, lack of transportation, or lack of abilities to
prepare food
• Consider referral to dietitian for individualized counseling
• Reinforce maintenance of normal body weight throughout lifetime
• Monitor weight weekly
Weight
• Limit foods that are high in calories, particular those that provide relatively few nutrients such as sugar-sweetened beverages
maintenance
and foods with high amounts fo fats and sugars
• Practice portion control through plate and serving size awareness
• Manage contributing treatment effects and risk factors as clinically indicated
Contributing psychosocial factors, including depression (See SANXDE-1)
Barriers to healthy food access such as living too far from grocery store, lack of transportation, or lack of abilities to prepare food
• Refer to community resources or PCP
• Refer to dietitian or weight management programs for individualized help as needed k
• Consider evaluation for bariatric surgery or pharmacologic therapym as appropriate (if obese or morbidly obese)
Weight lossk • Monitor weight daily
• Recommend weight loss of no more than 2 lbs per week and no more than 1 lb per week in survivors older than 64 years
• Limit foods that are high in calories, particularly those with relatively few nutrients such as sugar-sweetened beverages and foods
with high amounts of fat and sugars
• Substitute high-calorie foods with low-calorie, nutrient-dense foods such as water-rich/low-starch vegetables, broth-based soups,
whole grains, fresh fruits for desserts, and beverages such as water, unsweetened tea, and black coffee.
• Practice portion control by using smaller plates and restricting intake to one serving
gCoordination with primary care physicians and other involved providers is recommended.
jFor additional resources see the ASCO Toolkit on Obesity and Cancer: https://www.asco.org/practice-policy/cancer-care-initiatives/prevention-survivorship/obesity-
cancer and the LIVESTRONG My Plate Calorie Tracker: http://www.livestrong.com/myplate.
kModification of diet and dietary components should be done on an individual basis.
lStrongly consider for survivors with negligible weight loss from diet and exercise interventions.
mThe safety and efficacy of these drugs in cancer survivors is unknown. Lifestyle modifications are preferred over pharmacologic therapy.

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Survivorship Supplement Use
GENERAL PRINCIPLES OF SUPPLEMENT USE

• Supplement use is not recommended for most survivors, except in instances of documented deficiencies, inadequate diet, or comorbid
indications (eg, osteoporosis, ophthamologic disorders, cirrhosis).
• Little data exist to support the use of vitamins or other dietary supplements for the purposes of cancer control, recurrence, or prevention.
• Taking vitamin supplements does not replace the need for adhering to a healthy diet. All efforts should be made to obtain nutrients from
dietary intake.a
• Providers should assess supplement use at regular intervals. Ask about reasons for supplement use and supplement ingredients.b
• Refer survivors using multiple and/or or unfamiliar supplements to a registered nutritionist/dietitian, preferably one with oncology
credentials.
• Survivors of certain cancers are at risk for vitamin deficiencies based on their cancer treatment. Deficiencies should be assessed and
repleted as needed (for example, See GAST-I 2 of 3 from the NCCN Guidelines for Gastric Cancer).
aReferral
to registered dietitians, especially those who are Certified Specialists in Oncology Nutrition (CSO) , should be considered for guidance in supplement use, if
deemed necessary.
bConsider use of available resources for information on supplements (See SURV-B 2 of 3).

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Survivorship Immunizations and Infections
GENERAL PRINCIPLES OF IMMUNIZATIONS

• These principles apply to cancer survivors, including those with hematologic or solid tumor malignancies and those post transplant.
• Clinicians should consider and encourage the administration of inactivated vaccines (eg, influenza) or vaccines made of purified antigens
(eg, pneumococcus), bacterial components (eg, diphtheria-tetanus-pertussis), or genetically engineered recombinant antigens
(eg, hepatitis B) in all cancer and transplant survivors. In the absence of known harm, administration of inactivated vaccines with the hope of
achieving some protection may be worthwhile. The usual doses and schedules are recommended.a,b,c
Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States https://www.cdc.gov/vaccines/schedules/
downloads/adult/adult-combined-schedule.pdf
• Vaccines as a strategy to prevent infection represents a unique challenge in cancer and transplant survivors. Vaccines may not trigger
protective immune responses in actively immunocompromised individuals or in survivors with residual immune deficits. In addition, certain
vaccines such as those that are live attenuated (eg, zoster, MMR) are contraindicated in actively immunosuppressed individuals because of
a proven or theoretical increased risk of prolonged shedding and disease from the live organism present in the vaccine; other live attenuated
vaccines might also be contraindicated in survivors’ close contacts. When other vaccine options exist, they should be preferred over live
attenuated vaccines in survivors (eg, recombinant zoster vaccine).
• Ideally, clinicians should have administered all indicated vaccines to patients before initiation of cancer treatment (if possible, at least 2
weeks before cancer treatment).e
Inactivated or recombinant vaccines should be administered 2 or more weeks before cancer treatment and 3 or more months after cancer
chemotherapy. While this schedule is preferred, the inactivated influenza vaccine can be administered during cancer treatment.
Live viral vaccinesd can be administered 4 or more weeks before cancer treatment or 3 or more months after cancer chemotherapy, but
consultation with an infectious disease specialist or physician familiar with vaccination in survivors and/or patients with cancer is strongly
recommended.
• In survivors who received anti–B-cell antibody therapy, vaccination should be delayed for at least 6 months after chemotherapy and the last
dose of such therapy.
aNational Center for Immunization and Respiratory Diseases. General recommendations on immunization — recommendations of the Advisory Committee on
Immunization Practices (ACIP). MMWR Recomm Rep 2011;60:1-64. Available at: http://www.ncbi.nlm.nih.gov/pubmed/21293327.
bAlso see: Freedman MS, Hunter P, Ault K, Kroger A. Advisory Committee on Immunization Practices recommended immunization schedule for adults aged 19 years or
older - United States, 2020. MMWR Morb Mortal Wkly Rep 2020;69:133-135.
cRubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58:309-318.
dSee Vaccines Contraindicated or to Be Used With Caution in Actively Immunocompromised Survivors or In Close Contacts of Immunocompromised Survivors
(SIMIN-A).
eCancer treatment includes chemotherapy, surgery, treatment with immunosuppressive drugs, radiation, and splenectomy.

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RISK ASSESSMENT INTERVENTIONS

AND SCREENING
• Education on infection prevention practices

Risk factors for infections: Safe pet care/avoidance of zoonosisg
• Underlying disease Travel precautionsh
• Post-splenectomy Gardening precautionsi
• Prior chemotherapy Proper hand hygienej
• Monoclonal antibodies • Vaccinesd,k
(eg, rituximab, alemtuzumab) Assess overall immune system viability and history of allergic
• Prior radiation reactions to vaccines
• Corticosteroids ◊ Baseline white blood cell count (WBC) should be adequate See SIMIN-3
• Prior cellular therapies before starting vaccinations, unless elevated due to disease
Hematopoietic cell status
transplantation (HCT)f ◊ Patient should not be on immunosuppressive drugsl or
CAR T-cell therapy chemotherapy
• Prior/current exposure to endemic ◊ Ongoing infection should not be present
infections or epidemics • Antimicrobial prophylaxis
• Blood transfusion history (See NCCN Guidelines for Prevention and
Treatment of Cancer-Related Infections)
dSee Vaccines Contraindicated or to Be Used With Caution in Actively Immunocompromised Survivors or In Close Contacts of Immunocompromised Survivors
(SIMIN-A).
fHCT includes peripheral blood stem cell transplantation, bone marrow transplantation (BMT), and cord blood transplantation.
gSafe pet care tips include washing hands with soap and running water after handling animal feces. If possible, survivors at high risk for immune suppression should
avoid direct contact with animal feces and other bodily secretions. Survivors with elevated risk of infection and those who are immunocompromised are at higher risk
for zoonoses and should use extra caution.
hTravel precautions include education on the need for pre-travel vaccines, prophylaxis against specific infections, and education on how to prevent waterborne,
airborne, and zoonotic infections. Travelers may find useful information at https://wwwnc.cdc.gov/travel/yellowbook/2020/travelers-with-additional-considerations/
immunocompromised-travelers or by consulting a travel clinic.
iExamples of gardening precautions include:
• Wearing gloves to avoid skin cuts/punctures that could have delayed healing and to avoid thorns that can have fungus or staphylococcus/streptococcus.
• Wearing a protective mask to avoid spores. (For guidelines on physical activity, see [SPA-1])
jFor proper hand hygiene, see the Centers for Disease Control and Prevention (CDC) "Clean Handwashing: Clean Hands Save Lives" campaign https://www.cdc.gov/
handwashing/.
kFor dosing and schedule, See General Principles of Vaccines in Cancer Survivors (SIMIN-B).
lPatients should not be on immunosuppressive drugs including ≥0.5 mg/kg of prednisone or equivalent, or greater than a combination of two immunosuppressive
medications given concurrently.

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VACCINE TYPEd,j TREATMENTk

• Inactivated influenza vaccine (IIV) or recombinant influenza
vaccine (RIV) recommended annuallyo
Recommended for • Tetanus, diphtheria, pertussis (Tdap)
all cancer survivors • Recombinant zoster vaccine in all survivors 50 years or older
• Human papillomavirus (HPV) in previously unvaccinated
adults through 45 years of age
• Pneumococcal vaccinep
Inactivated, purified antigensl • Hepatitis B
or 2 doses of hepatitis B vaccine, recombinant (adjuvanted)
Bacterial componentsl given at least 4 weeks apart or
3 doses of a different hepatitis B vaccine (at 0, 1, and 6
months) 40 mcg/mL
• Hepatitis A
Recommended if some
2 doses of single-antigen hepatitis A vaccine or
special circumstance or
3-dose series of combination hepatitis A and hepatitis B
risk factor is presentn
vaccine
• Haemophilus influenzae type b
• Meningococcusq
• Typhoid bacterial capsular polysaccharide
• Inactivated polio vaccine (IPV)
• Japanese encephalitis
• Rabies virus
dSee Vaccines Contraindicated or to Be Used With Caution in Actively
pPCV-13 and PPSV-23 are recommended for adults 65 years or older and for younger
Immunocompromised Survivors or In Close Contacts of Immunocompromised
Survivors (SIMIN-A). adults who are immunocompromised (ie, HCT and functional or anatomic asplenia)
kFor dosing and schedule, See General Principles of Vaccines in Cancer Survivors or for lung cancer survivors or those who had lung resection. [Matanock A, Lee G,
(SIMIN-B). Gierke R, et al. Use of 13-valent pneumococcal conjugate vaccine and 23-valent
mnactivated or purified antigens or bacterial components should be administered pneumococcal polysaccharide vaccine among adults aged ≥65 years: Updated
beginning at least 3 months after chemotherapy or radiation therapy and 6 months recommendations of the Advisory Committee on Immunization Practices. MMWR
after HCT (a dose of inactivated influenza vaccine can be given as early as 4 months Morb Mortal Wkly Rep 2019;68:1069-1075; and Centers for Disease Control and
after HCT, but a second dose should be considered in this situation). Prevention (CDC). Use of 13-valent pneumococcal conjugate vaccine and 23-valent
nThese vaccines should be considered if there are unique circumstances such as pneumococcal polysaccharide vaccine for adults with immunocompromising
functional or anatomic asplenia or in patient's lifestyle, upcoming travel, or local conditions: recommendations of the Advisory Committee on Immunization Practices
epidemic or risks that merit their use. Please consult with an infectious disease (ACIP). MMWR Morb Mortal Wkly Rep 2012;61:816-819.]
or travel medicine specialist. Vaccination precautions for survivors who had qRecommended in high-risk patients or those with functional or anatomic
hematopoietic cell transplant can be found on SIMIN-B (2 of 3). asplenia. Committee on Infectious Diseases. Recommendations for serogroup B
oSee Principles of Influenza Vaccine(s) (SIMIN-C). meningococcal vaccine for persons 10 years and older. Pediatrics 2016;138.

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VACCINES CONTRAINDICATED OR TO BE USED WITH CAUTION

IN ACTIVELY IMMUNOCOMPROMISED SURVIVORS
OR
TO BE USED WITH CAUTION IN CLOSE CONTACTS OF
IMMUNOCOMPROMISED SURVIVORS1
Live attenuated vaccinesa
• Measles, mumps, rubella (MMR)
• Varicella zosterb,c,d
• Oral typhoid
• Yellow fever
• Rotaviruse
Footnotes
aSevere complications have followed vaccination with live attenuated vaccines among immunocompromised patients. They should not be offered to an actively
immunocompromised or transplant survivor or their close contacts, unless cleared by a clinician experienced in vaccine use or by an infectious disease specialist.
If a live attenuated vaccine is inadvertently administered to a survivor's close contact, close contact with the survivor should be avoided for 2 to 6 weeks following
vaccination depending on the type of administered vaccine.
bA new recombinant zoster vaccine has become available in the United States and should be considered the preferred zoster vaccine for cancer survivors. For
additional recommendations regarding zoster vaccine, see Principles of Zoster (Shingles) Vaccine Use in Cancer or Transplant Survivors (SIMIN-D).
cImmunocompromised patients should avoid contact with persons who develop skin lesions after receipt of varicella or zoster vaccine, until the lesions clear.
dThere are 3 vaccines that contain live attenuated varicella zoster virus: Varicella Virus Vaccine Live (VAR) is a single-antigen vaccine indicated for active immunization
for the prevention of varicella in individuals 12 months of age and older; Measles, Mumps, Rubella and Varicella Virus Vaccine Live (MMRV) is indicated for active
immunization for the prevention of measles, mumps, rubella, and varicella in children 12 months through 12 years of age; and Zoster Vaccine Live (ZVL) is indicated
for prevention of herpes zoster (shingles) in individuals 50 years of age and older.
eImmunocompromised survivors should avoid handling diapers of children who have been vaccinated with rotavirus vaccine for 4 weeks after vaccination.
References
1Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58:309-318.

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GENERAL PRINCIPLES OF VACCINES IN CANCER SURVIVORS

Vaccination in Non-Transplant Survivors1,2
• These principles apply to survivors of hematologic or solid tumor malignancies except those receiving anti–B-cell antibodies.a
• The following vaccines can be administered to cancer survivors:

Influenza vaccine annually (See Principles of Influenza Vaccine(s) SIMIN-C)
Pneumococcal vaccine
◊ Recommended for adults 65 years or older and for younger adults who are immunocompromised1
◊ 13-valent pneumococcal conjugate vaccine (PCV13) x 1 dose if never vaccinated against pneumococcus
◊ 23-valent pneumococcal polysaccharide vaccine (PPSV23) should be administered at least 8 weeks after the indicated dose(s) of PCV13.
◊ For those who received PPSV23, PCV13 should be administered ≥1 year after the last PPSV23 dose.
◊ A second dose of PPSV23 is recommended 5 years after the first dose for immunocompromised survivors and those with functional or
anatomic asplenia.
Tetanus, diphtheria, pertussis vaccine (Td/Tdap):
◊ Administer a one-time dose of Tdap to adults younger than 65 years of age who have not received Tdap previously or for whom vaccine
status is unknown to replace one of the 10-year Td boosters (substitute 1-time dose of Tdap for Td booster; then boost with Td every 10
years). Otherwise administer Td booster every 10 years.
◊ Consider administering a Tdap booster every 5 years.
Human papillomavirus (HPV) vaccine in adult survivors through age 45 years. For dosing and schedules see
https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/hpv.html
Footnotes
aIn survivors who received anti–B-cell antibody therapy, the above vaccines can be given, but should be delayed for at least 6 months after chemotherapy and the last
dose of such therapy.
References
1Centers for Disease Control and Prevention (CDC). Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults
with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2012;61:816-
819 https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6140a4.htm
2Freedman MS, Hunter P, Ault K, Kroger A. Advisory Committee on Immunization Practices recommended immunization schedule for adults aged 19 years or older -
United States, 2020. MMWR Morb Mortal Wkly Rep 2020;69:133-135.
Continued
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Vaccination in Survivors Who Had Cellular Therapy (ie, HCT, CAR T-cell therapy)b,3
• For infection concerns and recommended prophylaxis for immune- • Hepatitis B (HepB) vaccine
targeted agents, see NCCN Guidelines for Prevention and Treatment of Two doses of HepB vaccine, recombinant (adjuvanted) given at least
Cancer-Related Infections. 4 weeks apart or three doses of HepB vaccine should be administered
• Influenza vaccine annually 6–12 months after HCT.
(See Principles of Influenza Vaccine(s) SIMIN-C) 3 doses of a different hepatitis B vaccine (at 0, 1, and 6 months)
One dose should be administered annually to all cancer survivors 40 mcg/mL
starting 6 months after HCT and starting 4 months after if there is If a postvaccination anti-hepatitis B surface antigen (anti-HBsAg)
a community outbreak of influenza as defined by the local health concentration of ≥10 mIU/mL is not obtained, a second series of HepB
department. vaccine is recommended.
• Pneumococcal vaccine 1st dose of HepB vaccine (after which anti-HBs is tested) using high
Three doses (1 month apart) of PCV13 should be administered dose (40 μg) should be administered.
3–6 months after HCT. • Inactivated polio vaccine (IPV)
At 12 months after HCT, 1 dose of PPSV23 should be given provided the Three doses of IPV vaccine should be administered 6–12 months after
patient does not have chronic graft-versus-host disease (GVHD). HCT
For patients with chronic GVHD, a fourth dose of PCV13 can be given at • Human papillomavirus (HPV) vaccine
12 months after HCT. Administration of 3 doses of HPV vaccine 6–12 months after HCT for
• Haemophilus influenzae type b (Hib) vaccine adult survivors through age 45 years.
Three doses of Hib vaccine should be administered 6–12 months after • Live viral vaccines should not be administered to HCT survivors
HCT. with active GVHD or ongoing immunosuppression. They should only
• Meningococcal conjugate vaccine quadrivalent (MCV4) be administered to HCT survivors without active GVHD or ongoing
The MCV4 vaccine may be considered in outbreak situations or in immunosuppression following consultation with an infectious diseases
endemic areas. specialist.
The MCV4 vaccine is appropriate for splenectomized/functional asplenia Measles, mumps, rubella (MMR) vaccine
survivors ◊ MMR vaccine should be avoided within 4 weeks before HCT.
• Tetanus, diphtheria, pertussis vaccination 4 ◊ A 2-dose series of MMR vaccine should be administered to measles-
Three doses of DTaP vaccine should be administered 6–12 months after seronegative adolescents and adults 24 months after HCT in patients
HCT (administer the first 2 doses at least 4 weeks apart and the third with neither chronic GVHD nor ongoing immunosuppression and 8–11
dose 6–12 months after the second). This three-dose regimen should be months after the last dose of immune globulin intravenous (IGIV).
followed by Td boosters every 10 years. Zoster vaccine (VAR)
Alternatively, one dose of Tdap and 2 doses of DT or one dose of Tdap ◊ The new recombinant zoster vaccine is recommended, but the
and 2 doses of Td can be given. VAR vaccine may be used if patients have normal immunity and
recombinant zoster is not available. (see SIMIN-D)
◊ A 2-dose series of recombinant zoster vaccine or VAR should be
Footnotes
bHCT includes peripheral blood stem cell transplantation, bone marrow transplantation (BMT), administered 24 months after HCT to varicella-seronegative patients
and cord blood transplantation.
with neither GVHD nor ongoing immunosuppression and 8–11
months after the last dose of IGIV.
References
https://www.ncbi.nlm.nih.gov/pubmed/24421306.
Continued
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Vaccines Considered Safe for Cancer and Transplant Survivors and Close Contactsc
Inactivated or purified antigens or bacterial componentsd Recombinant viral antigens
• Influenza: inactivated influenza virus vaccinee • Hepatitis B
Trivalent (IIV3), standard dose • Human papillomavirus (HPV)
Trivalent (IIV3), high dose • Recombinant trivalent influenza vaccine (RIV3)e
Quadrivalent (IIV4), standard dose • Zoster (RZV)
• Pneumococcus:
Pneumococcal conjugate vaccine (PCV)
PPSV
• Meningococcus:
Quadrivalent meningococcal conjugate vaccine
(MCV4: serotypes A, C, W, Y)
Meningococcal vaccine (serotype B)3
• Tetanus, diphtheria, pertussis (Td/Tdap)
• Hepatitis A
• Haemophilus influenzae type b
Footnotes
cIdeally, clinicians should have administered all indicated vaccines to patients at least 2 weeks before initiation of cancer treatment (ie, chemotherapy, surgery, treatment
with immunosuppressive drugs, radiation, splenectomy).
dFor patients traveling to endemic countries, vaccines such as typhoid bacterial capsular polysaccharide, inactivated polio vaccine (IPV), Japanese encephalitis, and
rabies virus are recommended by the Centers for Disease Control and Prevention (www.cdc.gov).
eAdministration of the flu vaccine to survivors with egg allergy symptoms (other than hives) should be done at a center that can manage severe allergic reactions.
Grohskopf LA, Alyanak E, Broder KR, et al. Prevention and control of seasonal influenza with vaccines: Recommendations of the Advisory Committee on Immunization
Practices - United States, 2019-20 influenza season. MMWR Recomm Rep 2019;68:1-21.
References
3Folaranmi T, Rubin L, Martin SW, Patel M, MacNeil JR; Centers for Disease Control (CDC). Use of serogroup B meningococcal vaccines in persons aged ≥10 years at
increased risk for serogroup B meningococcal disease: recommendations of the Advisory Committee on Immunization Practices, 2015. MMWR Morb Mortal Wkly Rep
2015 Jun 12;64(22):608-612.

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PRINCIPLES OF INFLUENZA VACCINE(S)1,2

• Annual influenza vaccination is recommended2 for all cancer and transplant survivors. Live attenuated influenza vaccines should be avoided
in these individuals unless they have been cleared to do so by an infectious disease specialist or physician familiar with vaccination in this
population.
• For a summary of recommendations for prevention and control of influenza with vaccines see:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713402/
• Components of the influenza vaccine are determined each year by the World Health Organization (WHO) according to reports of the most
common influenza viruses that are likely to circulate that year.
• Influenza vaccines can be inactivated or recombinant. They may contain standard or higher doses of the antigen. They can be trivalent or
quadrivalent.
Preferred Vaccines
• Inactivated influenza vaccine
Trivalent (IIV3), standard dose
Trivalent (IIV3), high dose
Quadrivalent (IIV4), standard dose
• Recombinant influenza vaccinea
Trivalent (RIV3)
Quadrivalent (RIV4)
To date, there is no evidence that one vaccine is superior to any other vaccine.
Footnotes
aAdministration of the flu vaccine to survivors with egg allergy symptoms (other than hives) should be done at a center that can manage severe allergic reactions.
Grohskopf LA, Alyanak E, Broder KR, et al. Prevention and control of seasonal influenza with vaccines: Recommendations of the Advisory Committee on Immunization
References
1Freedman MS, Hunter P, Ault K, Kroger A. Advisory Committee on Immunization Practices recommended immunization schedule for adults aged 19 years or older -
United States, 2020. MMWR Morb Mortal Wkly Rep 2020;69:133-135.
2Grohskopf LA, Alyanak E, Broder KR, et al. Prevention and control of seasonal influenza with vaccines: Recommendations of the Advisory Committee on Immunization

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PRINCIPLES OF ZOSTER (SHINGLES) VACCINE USE IN CANCER OR TRANSPLANT SURVIVORS1,2

Recombinant zoster vaccine (Preferred)
• A new recombinant zoster vaccine has become available in the United States. The recombinant vaccine is the preferred zoster vaccine for cancer
survivors, and is recommended for survivors aged 50 years and older.
• In survivors who have previously received the live attentuated zoster vaccine, immunization with recombinant zoster vaccine should be
considered. The recombinant vaccine should not be given less than 2 mo after receiving the live attenuated vaccine.
Live attenuated zoster vaccine
• Although the recombinant zoster vaccine is preferred, the live attenuated zoster vaccine can be given if the recombinant vaccine is unavailable or
access to the recombinant vaccine is an issue.
• Live attenuated zoster vaccine may be considered in survivors with a history of solid tumors or leukemia whose disease is in remission, who have
restored their immunocompetence, and who have not received chemotherapy or radiation for at least 3 months.
• If live attenuated zoster vaccine is given prior to starting therapy, it should be administered at least 4 weeks prior to the first dose of
immunosuppressive therapy.2
• The vaccine can be administered to select immunocompetent survivors regardless of whether they report a prior episode of herpes zoster.a
• Licensed antiviral medications active against members of the herpes virus family (eg, acyclovir, famciclovir, valacyclovir, valganciclovir) might
interfere with replication of the live, varicella zoster virus (VZV)-based zoster vaccine.b
• A single dose of live attenuated zoster vaccine is recommended for cancer or transplant survivors 60 years of age and older assuming that active
or ongoing immunodeficiency is not present and that there is no history of cellular immunodeficiency.
For survivors aged 50–59 years, live attenuated zoster vaccination should be considered in those with a history of varicella or zoster infection or
VZV seropositive with no previous doses of varicella vaccine.
• Live attenuated zoster vaccine should be avoided:
in patients with lymphomas, other malignant neoplasms affecting the bone marrow or lymphatic system, or a history of cellular
immunodeficiency;
in patients on immunosuppressive therapy, including high-dose corticosteroids (>20 mg/day of prednisone or equivalent) lasting 2 or more
weeks; and
in patients undergoing or with history of HCT. The experience of HCT recipients with VZV-containing vaccines (eg, zoster vaccine) is limited.
Physicians should assess the immune status of the recipient on a case-by-case basis to determine the relevant risks. If a decision is made to
vaccinate with zoster vaccine, the vaccine should be administered at least 24 months after transplantation in patients without active GVHD or
enhanced immunosuppression.
Footnotes
aZoster vaccination is not indicated to treat acute zoster, to prevent persons with acute zoster from developing postherpetic neuralgia (PHN, a common complication of zoster
that results in chronic, often debilitating pain that can last months or even years), or to treat ongoing PHN. Before routine administration of zoster vaccine, it is not necessary
to ask patients about their history of varicella (chickenpox) or to conduct serologic testing for varicella immunity. Dooling KL, Guo A, Patel M, et al. Recommendations of the
Advisory Committee on Immunization Practices for use of herpes zoster vaccines. MMWR Morb Mortal Wkly Rep 2018;67:103-108.
bSurvivors taking chronic acyclovir, famciclovir, valacyclovir, or valganciclovir should discontinue these medications at least 24 hours before administration of zoster vaccine.
These medications should not be used for at least 2 weeks after vaccination, by which time the immunologic effect should be established.
References
1Dooling KL, Guo A, Patel M, et al. Recommendations of the Advisory Committee on Immunization Practices for use of herpes zoster vaccines. MMWR Morb Mortal Wkly Rep
2018;67:103-108. https://www.cdc.gov/mmwr/volumes/67/wr/mm6703a5.htm

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Late Effects/Long-Term
Psychosocial and Physical
Problems

Table of Contents
Survivorship Cardiovascular Disease Risk Assessment
PRINCIPLES OF CARDIOVASCULAR DISEASE RISK ASSESSMENT

• Cardiovascular disease (CVD) remains a leading cause of death in cancer survivors. The risk of CVD-related death varies with years from
diagnosis, with most survivors being at greatest risk 5 or more years after diagnosis and completion of curative therapy.
• Shared risk factors for both cancer and CVD (ie, smoking, poor health behaviors) contribute to the development of CVD and structural heart
disease or heart failure, a concept that becomes especially relevant to cancer survivors. Attention and counseling regarding shared risk
factors may improve cancer- and cardiovascular-related outcomes.
• Cancer treatments (cytotoxic and targeted systemic therapies,a radiation therapy) can result in diverse cardiovascular issues, including
cardiomyopathy, hypertension, hyperlipidemia, cardiac arrhythmia, myocardial infarction, and cerebrovascular accidents. Survivors treated
with anthracyclines may be at increased risk for heart failure. (See SCARDIO-1)
• Most cardiovascular diseases (such as atherosclerosis) develop over time as a result of well-defined risk factors such as hypertension,
hyperlipidemia, tobacco abuse, obesity and diabetes. Control of these risk factors can decrease the risk of subsequent cardiovascular
events.
• Survivors should be assessed throughout the survivorship continuum for:
Pre-existing and emerging CVD (eg, coronary artery disease [CAD], congestive heart failuree [CHF], peripheral vascular disease,
arrhythmias including atrial fibrillation) and CVD risk factors (eg, hypertension, dislipidemia, obesity, cigarette/tobacco use, diabetes
mellitus), with intervention for modifiable risk factors as necessary
Cancer treatment history (eg, regimen/dose,a radiation field)
Diet and exercise habits, cigarette/tobacco use
• Tools exist to help quantify atherosclerotic CVD (ASCVD) risk (eg, ASCVD risk scoreb).
• Survivors should be counseled on any increased risk of CVD they may have based on prior treatment, comorbidity, or CVD risk factors and
on the ABCDEs of CVD Prevention. (See Table 1 on SCVD-2)
• Cooperation and shared care with primary care providers, and cardiovascular specialists as needed, is key to optimizing cardiac and
vascular outcomes in cancer survivors.
• Consider referral to cardio-oncology or a cardiology specialist for high-risk survivors.
aHER2-directed
therapy, VEGF signaling pathway inhibitors, cisplatin, anthracyclines with or without taxanes, and androgen deprivation therapy are CVD risk
factors.
bThe ASCVD Risk Estimator Plus from the American College of Cardiology is available at http://tools.acc.org/ascvd-risk-estimator-plus/#!/calculate/estimate/.

SCVD-1

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Survivorship Cardiovascular Disease Risk Assessment
PRINCIPLES OF CARDIOVASCULAR DISEASE RISK ASSESSMENT
Table 1: ABCDEs to Promote Cardiovascular Wellness in Cancer Survivorsc

A • Awareness of risks and presentation of heart disease
• Assessment of cardiovascular disease and cardiovascular risk
• Aspirin use as appropriate (indicated for secondary prevention; clinician-survivor discussion
required for primary prevention with careful weighing of benefits and risks)
B • Blood pressure monitoring/management (with clinician-survivor discussion regarding the use of
hypertension treatment and blood pressure goals)
C • Cholesterol assessment/management (with clinician-survivor discussion regarding the use of
statin therapy for primary prevention and lipid profile goals)
• Cigarette/tobacco cessation (See NCCN Guidelines for Smoking Cessation)
D • Diet and weight management (See SNWM-1)
• Dose (cumulative) of anthracyclines and/or radiation to heart
• Diabetes mellitus prevention/treatment
E • Exercise (See SPA-1)
• Echocardiogram and/or EKG based on individual risk
cAdapted with permission from Montazeri K, Unitt C, et al. ABCDE Steps to Prevent Heart Disease in Breast Cancer Survivors. Circulation 2014;130:e157-e159.

SCVD-2

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Survivorship: Anthracycline-Induced Cardiac Toxicity Discussion
PRINCIPLES OF ANTHRACYCLINE-INDUCED CARDIAC TOXICITY

• Cancer treatments can result in diverse cardiovascular issues (See SCVD-1). This algorithm focuses specifically on heart failure or
cardiomyopathy that may arise from anthracycline therapy. Other systemic therapies may also cause cardiomyopathy (eg, HER2-targeted
therapies), and some of the concepts presented in these recommendations may apply to these other cardiomyopathies.
• Anthracycline-induced heart failure may take years or even decades to manifest. Data suggest that signs of cardiac dysfunction can be
seen prior to the development of symptoms. If detected early, anthracycline-induced heart failure may be responsive to cardioprotective
medications, although prospective studies evaluating these medications are lacking.
• Survivors may have risk factors that predispose them to heart failure. Some survivors may have structural heart disease (such survivors
are considered to have Stage B heart failure) even if they have no actual symptoms. A history of anthracycline exposure is a risk factor that
predisposes survivors to cardiac disease.a (See SCARDIO-3).
• Having a history of anthracycline exposure plus additional cardiovascular risk factors increases the risk of developing cardiomyopathy and
heart failure. It is encouraged that such survivors should have heart failure risk factors, including hypertension, dyslipidemia, and diabetes
addressed in coordination with primary care.
• The risk for cardiovascular problems varies greatly depending on the type of anthracycline used and the cumulative dose received.
• For this algorithm, the panel has placed an emphasis on early recognition and prevention of clinical heart failure, as well as early treatment
of patients at risk with appropriate cardioprotective medications to prevent cardiac remodeling over time. Therefore, for high-risk survivors,
the panel emphasizes the need for a thorough clinical screening for heart failure within one year after completion of anthracycline therapy.
aYancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/
American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;62:e147-e239.

SCARDIO-1

Table of Contents
INITIAL CLINICAL ASSESSMENT FOR PATIENTS WHO HAVE

RECEIVED PREVIOUS ANTHRACYCLINE THERAPY
• Cardiovascular • Workup for
• History and physical (H&P) risk factor other causes of
Assess for signs and symptoms of heart failureb,c management No evidence of symptoms
Assess patient’s ability to perform routine and desired (see SCVD-1)d structural heart disease, • Referral to other
activities of daily living (ADLs) • Consider two- but symptomaticb specialties
Look for signs of volume overload dimensional (eg, pulmonology
• Review medications, alcohol use, and other substance use echocardiogram or cardiology)
• Review oncologic history (ECHO) with
Review total cumulative dose of anthracycline doppler flow
Other systemic therapy and/or chest radiation therapy study within
• Evaluate for presence of heart failure risk factors 1 year after No evidence of
Hypertension completion of structural heart disease
Dyslipidemia anthracycline and asymptomatic See Stage A
Diabetes mellitus therapy for or (SCARDIO-3)
Family history of cardiomyopathy survivors No ECHO performed
Age >65 years withc,e,f and asymptomatic
High cumulative anthracycline dose (ie, cumulative High
doxorubicin dose at or higher than 250 mg/m2 or cumulative
equivalent) anthracycline Evidence of structural heart
Low-normal LVEF (50%–54%) at baseline dose disease (asymptomatic or
History of other cardiovascular comorbidities Low cumulative symptomaticb):
(ie, atrial fibrillation, known coronary artery disease anthracycline Determine stage of
• Left ventricular (LV)
[CAD], baseline evidence of structural heart disease) dose and 1 or cardiomyopathy
dysfunction
more (heart failure)
Smoking • LV hypertrophy
heart failure (See SCARDIO-3)
Obesity • Valvular disease
risk factors • LV dilatation and/or wall
thinning
bSigns and symptoms of heart failure include: shortness of breath or chest pain after physical activity or exercise, shortness of breath when sleeping, waking up at night
due to shortness of breath, and swelling in the legs.
cPatients with symptoms of heart failure should undergo an echocardiogram.
dEncourage primary care provider involvement in treatment of cardiovascular risk factors and encourage routine follow-up in coordination with primary care provider.
eReferral to cardiologist/cardio-oncologist if there are echocardiographic abnormalities.
fFor survivors of certain cancer types, longer-term cardiovascular surveillance may be needed. Please see the NCCN Guidelines for Treatment of Cancer by Site for
specific monitoring recommendations.

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Table of Contents
STAGES OF CARDIOMYOPATHY (HEART FAILURE)g TREATMENT SURVEILLANCE

Stage A
(No structural disorder of the heart, but at risk of developing heart • Address underlying risk factors
failure)g,h,i (hypertension, lipids, cigarette/tobacco
• Patients may have any of the following: use, obesity, metabolic syndrome,
History of potentially cardiotoxic chemotherapyj diabetes)d
(including anthracyclines) • Recommend regular physical activity and
History of chest irradiation (especially mantle and left-sided) healthy diet habits (See HL-1)
Hypertension, CAD, diabetes mellitus • Consider referral to cardiologist for
History of alcohol abuse, personal history of rheumatic fever, managementj
family history of cardiomyopathy
Reassess based
Stage B on symptoms
(Structural heart disease but no signs or symptoms of heart failure)g
• Patients may have any of the following:
• Measures under Stage A as appropriate
LV hypertrophy
• Referral to cardiologist for management
LV dilatation or hypocontractility
Asymptomatic valvular heart disease
Previous myocardial infarction
Stage C
(Signs and symptoms of heart failure with
underlying structural heart disease)g
Stage D Referral to cardiologist for management
(Advanced structural heart disease and marked symptoms
of heart failure at rest despite maximal medical therapy and
requiring specialized interventions)g
dEncourage primary care provider involvement in treatment of cardiovascular risk factors and encourage routine follow-up in coordination with primary care provider.
gYancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the Amercian College of Cardiology Foundation/
American Heart Association Task Force on practice guidelines. Circulation 2013;128:e240-e327.
hConsider use of biomarkers in select patients at high risk for heart failure (Stage A) (See Discussion).
iAny patient who has received potentially cardiotoxic chemotherapy and/or chest radiation (and specifically anthracycline-based chemotherapy) should be considered
Stage A cardiomyopathy.
jFor a list of potentially cardiotoxic chemotherapy agents, see Moslehi JJ. Cardiovascular toxic effects of targeted cancer therapies. N Eng J Med 2016;375:1457-1467.
kConsider referral to a cardiologist, especially if additional anthracycline therapy or other cardiotoxic treatment is needed.

SCARDIO-3

Table of Contents
Survivorship Anxiety, Depression, Trauma, and Distress
GENERAL PRINCIPLES OF ANXIETY, DEPRESSION, TRAUMA, AND DISTRESS

• The NCCN Guidelines for Distress Management define distress as “a multifactorial unpleasant emotional experience of a psychological (ie,
cognitive, behavioral, emotional), social, spiritual, and/or physical nature that may interfere with the ability to cope effectively with cancer, its
physical symptoms, and its treatment.” The NCCN Guidelines for Survivorship complement the NCCN Guidelines for Distress Management.
• Survivors of cancer and its treatment are at elevated risk for mental health issues such as fear of recurrence, distress, anxiety, and
depression that may persist formany years after diagnosis.a
Fear of recurrence can lead to increased symptoms when surveillance testing or follow-up appointments are scheduled and increased
anxiety when physical symptoms occur that may or may not be similar to those experienced during the cancer diagnosis.
Medical, psychosocial, environmental, and psychiatric health factors may affect the mood of cancer survivors and need to be considered
when screening for distress, anxiety, and depression in survivors and deciding on treatment. (See SANXDE-6)
Recurrent worry, fear, thoughts, or images related to cancer events should be distinguished from obsessive compulsive disorders.
Repetitive, persisting thoughts, images, or behaviors or mental acts that a person is compelled to perform, aimed at reducing intense
anxiety or preventing a dreaded event require psychiatric referral for evaluation and treatment.
Monitor distress, especially at times of transitions in care, cancer surveillance, significant loss, other major life events, and with social
isolation.
◊ Patients may not appear to be distressed and should be encouraged to inform their health care provider when they are feeling increased
distress, anxiety, or depression. See DIS-B from the NCCN Guidelines for Distress Management.
Clinical assessments should include and evaluate psychosocial aspects of a survivor's background, including trauma (See SANXDE-7)
• This algorithm is intended for oncologists and other health care providers to screen for distress, anxiety, and depression in cancer
survivors, to provide steps for addressing these concerns with survivors, and to facilitate decisions about referral to specialists.
The algorithm is not intended as a psychiatric diagnosis and treatment tool.
The algorithm focuses on more common mood disorders after cancer; it does not screen or address treatment for psychiatric conditions
such as bipolar disorders, schizophrenia, personality disorders, or obsessive compulsive disorders.
• Decisions about treatment and referral will depend on the acuteness of onset of symptoms, their intensity, and safety of the survivor and
others. (See SANXDE-6 and SANXDE-A)
aLu D, Andersson TM, Fall K, et al. Clinical diagnosis of mental disorders immediately before and after cancer diagnosis: a nationwide matched cohort study in sweden.
JAMA Oncol 2016;1188-1196.

SANXDE-1

Table of Contents
SCREENING: ANXIETY AND DEPRESSION
Screening questionsb to be asked at regular intervals,

Screening for anxiety and post-
especially when there is a change in clinical status or
Nervous/anxious and traumatic stress disorder (PTSD)
treatment, or patient presents with multiple somatic
impact on quality of life symptoms
complaints:c
See (SANXDE-3 and SANXDE-4)
• In the past two weeks, on more days than not have
you:
Nervous/anxious
◊ had worries or fears related to your cancer?
◊ felt nervous, or worried about other things?
Sad/depressed
◊ had trouble controlling your worry?
and impact on quality of life
Sad/depressed Screening for depression
or
◊ had less interest or enjoyment in activities than See (SANXDE-5)
Mixed depressed/anxious
usual?
and impact on quality of life
◊ felt sad or depressed?
• Additional screening for impact of mood on quality
of life if “Yes” to any of the above:
had difficulty functioning or withdrawn from daily
activities because of these (above-mentioned)
feelings or problems?
had trouble sleeping (eg, staying asleep, falling No significant impact of
Rescreen at next visit
asleep, too much sleep)? b mood on quality of life
had difficulty concentrating? b
bA positiveresponse to any of the questions should result in further assessment. However, if a patient has an isolated problem with sleep or concentration in the
absence of other symptoms, see (SSD-1) or (SCF-1).
cIf the NCCN Distress Thermometer is used as a primary screening tool, these questions would follow for those survivors with an elevated level of distress.

SANXDE-2

Table of Contents
SCREENING: ANXIETY AND PANICd DIAGNOSIS

See Evaluation
≥3 symptoms and persisting (SANXDE-7)
more than 6 months: or
Anxiety Safety evaluationg Refer to mental
Consider general anxiety
Excessive anxiety and worry that is difficult to health services
disorder, PTSD symptoms,
control and ≥3 of the following: for evaluation
or adjustment disorder
• Restless or on edge and treatmenth
• Easily fatigued
<3 symptoms and/or
• Difficulty concentrating or mind going blank
persisting less than 6 months:
• Irritability
Adjustment disorder f See Screening
• Muscle tension
with anxious or mixed mood (SANXDE-6)
• Sleep disturbance
or
Other anxiety disorder
Panic
Sudden intense fear or discomfort that peaks within
minutes and ≥4 of the following:e
• Palpitations, pounding heart
• Sweating See Evaluation
• Trembling or shaking (SANXDE-7)
• Sensations of shortness of breath or smothering or
• Chest pain or discomfort Panic disorder Safety evaluationg Refer to mental
• Nausea or abdominal distress health services
• Feeling dizzy, lightheaded, unsteady for evaluation
• Chills or heat sensations and treatmenth
• Paresthesias (numbness or tingling)
• Feelings of unreality or being detached from oneself
• Fear of losing control
• Fear of dying
dThe following additional tools may be used for individual intensive screening for a specific problem: Anxiety: GAD7; Panic: Brief Patient Health Questionnaire,
item 2 a-e. Both tools can be found at http://www.phqscreeners.com.
eConsideration should be taken for evaluation of other medical causes to rule out alternative etiologies.
fDevelopment of emotional or behavioral symptoms in response to an identifiable stressor(s) occurring within 3 months of the onset of the stressor(s). (American
Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing.)
gSee Safety Evaluation for Anxiety and Depression (SANXDE-A).
hPsychiatrist, psychologist, advanced practice clinician, and/or social worker.

SANXDE-3

Table of Contents
SCREENING: POST-TRAUMATIC STRESS SYMPTOMS DIAGNOSIS

OR DISORDER (PTSD)i,j
• Assess risk factors for PTSD (See SANXDE-B)
• Diagnosis of PTSD requires symptoms from each of the following
4 categories
Exposure to traumatic events (eg, cancer diagnosis, treatment)k
and the following symptoms that cause clinically significant
distress or impairment in social interactions, capacity to work,
or other functioning for more than 1 month: • Post-traumatic stress See Evaluation
◊ Re-experiencing: repeated, disturbing memories, dreams, or symptoms impacting (SANXDE-7)
flashbacks (minimum 1 symptom) quality of life or
Safety
◊ Persistent avoidance: avoidance of distressing memories, • Consider PTSD l Refer to mental
evaluationg
thoughts, feelings, or external reminders of the cancer • Consider adjustment health services
experience (minimum 1 symptom) disorder/distress for evaluation and
◊ Negative alterations in mood or cognition: exaggerated (see SANXDE-6) treatmenth
negative beliefs about oneself or the world, feeling detached
or estranged from others, lack of positive emotions, feelings
of fear, horror, anger, guilt, or shame (minimum 2 symptoms)
◊ Arousal: hypervigilance (being super alert or watchful
or on guard), difficulty concentrating, sleep disturbance,
aggressiveness, risky or self-destructive behavior (minimum
2 symptoms)

iFor a complete list of screening symptoms review the American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.).
Arlington, VA: American Psychiatric Publishing.
jThe following additional tools may be used for screening: Primary Care PTSD Screen (PC-PTSD), 4 items,
http://www.ptsd.va.gov/professional/assessment/screens/pc-ptsd.asp; or full screening with the 20-item PTSD Checklist for DSM-5 (PCL-5), intended for use by
qualified health professionals with advanced graduate training in psychological diagnostic assessment:
http://www.ptsd.va.gov/professional/assessment/documents/ptsd_trauma_assessments.asp.
kPerson may directly experience the traumatic event, witness the event, learn of the event occurring to a close family member or friend, or experience repeated or
extreme exposure to aversive details of the trauma. Life-threatening illness or cancer or debilitating medical condition is not necessarily a traumatic event, but may be
in some cases. A history of PTSD prior to a cancer diagnosis increases risk for symptoms of PTSD to be associated with cancer treatment if experiences remind the
survivor of a prior traumatic event. A future trauma may also evoke traumatic cancer memories increasing post-traumatic stress symptoms.
lSee Risk Factors for PTSD (SANXDE-B).

SANXDE-4

Table of Contents
SCREENING: DEPRESSIONi,m,n DIAGNOSIS

Safety evaluationg
and Evaluate medical
factors (See
Consider symptoms of mania or history of Evaluation
For at least 2 weeks, at least mania with ≥3 of these symptoms: SANXDE-7)
half the time, having ≥5 of • Expansive or irritable mood Safety risk,
or
the following: • Increased energy or goal-directed activity mania, or
Refer to appropriate
• Depressed, sad, empty, • Inflated self-esteem or grandiosity psychosis
emergency mental
or hopeless mood or • Decreased need for sleep health services for
appearance • More talkative, pressured speech evaluation and
• Loss of interest or • Racing thoughts, flight of ideas treatmenth
pleasure in most activities • High-risk behaviors
Major
• Weight loss or gain
depressive and
disorder
• Psychomotor agitation or Consider any of these symptoms of psychosis:
(MDD) See Evaluation
retardation • Delusions
• Lack of energy (SANXDE-7)
• Auditory hallucinations No safety risk, or
• Feeling worthless or • Disorganized thinking/speech
having excessive guilt mania, or Refer to mental
• Abnormal behavior, catatonia psychosis health services
• Diminished concentration, • Diminished emotional expression
indecisiveness for evaluation and
• Lack of self-initiated activities treatmenth
• Thoughts of death, suicidal
ideation
Does not meet Adjustment disorder or other See Screening

MDD criteria depressive symptoms disorder (SANXDE-6)

mThe following additional tools may be used for individual intensive screening for a specific problem: Screening Tools: PHQ-9 or PHQ-2. The PHQ-2 is comprised of the
first two items of the PHQ-9 and can be used as an initial depression screening. If the patient responds affirmatively to either of these two items, the remaining 7 items
are asked. (Available at: www.phqscreeners.com and http://www.commonwealthfund.org/usr_doc/PHQ2.pdf).
nWhen screening, also take into consideration a survivor’s cultural differences at presentation (eg, somatization as expression of emotional distress).

SANXDE-5

Table of Contents
SCREENING: DIAGNOSIS
ADJUSTMENT
DISORDER/DISTRESSi,o
Moderate/severe See Evaluation (SANXDE-7)

adjustment disorder or
or Refer to mental health
Adjustment disorder
Distress impacting services for evaluation and
with anxious,
quality of life treatmenth
Emotional or behavioral depressed, or mixed
symptoms in response to mood
an identifiable stressor(s) or
Safety evaluationg
or Distress from trauma
Distress that interferes or stressors that do Mild adjustment
with the ability to cope not meet criteria for disorder
mood disorder or or See Nonpharmacologic
PTSD Distress not Interventions (SANXDE-8)
impacting
quality of life

oThe following additional tool may be used for screening distress level: NCCN Distress Thermometer Screening Tool [DIS-A]. A score of ≥4 indicates moderate/severe
distress: "On a scale of 0–10 how much distress have you been experiencing in the past week, including today with 0 = No Distress and 10 = Extreme Distress?”

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EVALUATION: ANXIETY, DEPRESSION, TRAUMA, AND DISTRESSp

Medical Factors (H&P Exam) Psychiatric/Emotional Factors Social/External Factors
• General review:
Illness status/progression
Medication changes/side effects
Presence of new or poorly controlled
symptoms (ie, pain, nausea, constipation)
Status of coexisiting medical conditions
• Environmental stressors and
Substance abuse
non–cancer-related factors:
History of prior major depression, anxiety • Symptom review based on the Management
Social isolation, living alone
disorder, or suicide attempt Survivorship Anxiety and and Treatment
Family and caregiver conflicts,
History of trauma Depression screening (See SANXDE-8)
roles, and responsibilities
Fatigue level (See SFAT-1) recommendations (See or
Spouse, intimate partner
Functional status SANXDE-2 through SANXDE-6); For mania,
relationship
Current coping strategies evaluate for anticipation/fear of psychosis,
Financial problems and limited
Sexual function (See SSF-1) recurrence in the setting of: extensive
insurance coverage
Infertility Active surveillance by psychiatric
Employment concerns
Other medical factors including cognitive oncology team history, or
Limited access to medical care
function (See SCF-1) New symptoms or findings moderate to
Adolescents, younger adults,
• Laboratory studies to consider: suggestive of recurrence high safety risk
lack of connection with peers
Metabolic studies Transitions in surveillance • Refer for
History of abuse (ie,
Infection workup and care psychiatric
emotional, physical, sexual)
Anemia with underlying deficiencies • Consider other major evaluation and
Spiritual, religious, or
Endocrine/hormonal status psychiatric disorders treatment
existential concerns
• Other studies as clinically indicated:
Other stresses
Neurologic:
◊ Central nervous system (CNS) imaging
◊ Neuropsychological testing
Cardiac: electrocardiogram (EKG), ECHO,
stress test (See SCARDIO-1)
Pulmonary function tests
Sleep evaluation (See SSD-1)
pThese are general factors/principles that affect anxiety, depression, trauma, distress, and adjustment that need to be considered when evaluating survivors.

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ANXIETY, DEPRESSION, TRAUMA, AND DISTRESS: MANAGEMENT AND TREATMENT

NONPHARMACOLOGIC INTERVENTIONS
• For all survivors:
Address treatable contributing factors
◊ Pain, sleep disturbance, fatigue, toxic metabolic/endocrine/other medical comorbidities, substance abuse
Provide reassurance that symptoms of worry, stress, anxiety, and depression are common problems among
cancer survivors and that these symptoms can be treated
Provide support and education to patient and family regarding normal recovery phases after treatment, common • Reevaluate
stresses, distress and fears, and strategies for managing uncertainty and distress symptoms and
Provide resources for social support networks and specific social, emotional, spiritual, intimacy, and practical function at next
problem needs, including online and mobile phone apps. Consider referral to social work services or patient visit
navigator (if available). (See SURV-B) • Revise referrals
Develop a plan for regular physical activity and healthy nutrition. (See HL-1) and interventions
if symptoms are
• For adjustment disorder or distress without safety risk, mania, or psychosis: persistent or
Refer to a therapist, preferably one with psycho-oncology training if available (ie, psychologist, psychiatrist, increased
social worker, advanced practice clinician, licensed therapist):
◊ Psychological or social factors interfering with prescribed care
◊ Social work for complex social factors
◊ Supportive normalizing of survivor's experience
◊ Cognitive behavioral therapy (CBT) (eg, mindfulness, behavioral activation, structured CBT groups, digital
modalities)
Consider
◊ Existential therapy related to values, meaning, and purpose in life pharmacologic
Consider referral to chaplain for spiritual support for religious conflict, concerns about death and afterlife, guilt, interventions
grief, and meaning and purpose in life (See SANXDE-9)
Consider integrative therapies (ie, mindfulness meditation, imagery/hypnosis, yoga)
Consider referral for couples, family, caregiver, or relationship counseling/support
• For moderate to severe intensity major depression, generalized anxiety, panic, or PTSD symptoms:
Refer for evaluation and treatment by a mental health professionalh
Consider pharmacologic and/or nonpharmacologic treatments
• For substance abuse:
Safety evaluation (SANXDE-A)
See DIS-21 from the NCCN Guidelines for Distress Management
Refer to substance abuse specialist

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ANXIETY, DEPRESSION, TRAUMA, AND DISTRESS: MANAGEMENT AND TREATMENT

PHARMACOLOGIC INTERVENTIONSq
• First-line treatment:
Selective serotonin reuptake inhibitors (SSRIs)
Serotonin-norepinephrine reuptake inhibitors (SNRIs):
◊ Consider for concomitant pain
◊ Consider for concomitant hot flashes
Monitor for potential side effects
Counsel survivor that it may take up to 2 to 6 weeks at a therapeutic dose for
SSRIs and SNRIs to take effect • Reevaluate distress and function at next visit
Benzodiazepines (BZD) • Revise referrals and interventions if distress
(ie, clonazepam, lorazepam): is persistent or increased
◊ For acute anxiety relief or while waiting for antidepressant to take effect
◊ Adjust dose once SSRIs or SNRIs are fully effective and symptoms are
partially or completely abated
Counsel survivor that symptoms of withdrawal may occur should any of the
above-mentioned medications be abruptly discontinued
• Consider referral to mental health professionalh for medication failure if
inadequate response to first-line treatment

qSee Principles of Pharmacologic Interventions (SANXDE-C).

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SAFETY EVALUATIONa
DANGER TO SELF OR OTHERS OR INABILITY TO CARE FOR SELF
Consider at elevated risk if survivor:
Has an organized plan for suicide or homicide
CONSIDER PROTECTIVE FACTORS TO
OR
BALANCE WITH RISKS:
Has suicidal or homicidal thoughts and, based on clinical judgment,
• Psychosocial protective factors
the survivor is at imminent risk of harm to self or others
Personal resources that increase resilience,
• Consider the following risk factors:
environmental support, or coping
Psychosocial risk factors
Strong interpersonal bonds to family/
◊ Previous attempts at suicide or self-injury (eg, cutting or
community
burning)
Reasonably safe and stable environment
◊ Personality dysfunction or bipolar disorder with impulsivity,
Help seeking
irritation, agitation, or aggression
Good impulse control and coping/problem-
◊ Family history or other exposure to suicide
solving skills
◊ Isolation
Sense of belonging, sense of identity, and
◊ Recent loss of important person or relationship breakdown
good self-esteem
◊ Depression
Cultural, spiritual, and religious beliefs Determine
◊ Loss of rational thinking
about the meaning and value of life risk level
◊ Fear of death or dying due to pain and suffering
Identification of future goals (See SANXDE-A
◊ Feeling hopeless or loss of control
Identifies reasons for living 2 of 3)
◊ Perceives self as a burden
Responsibility to family or others; living
◊ Access to firearms/weapons
with family
◊ Financial instability
Supportive social network or family
◊ Alcohol or other substance abuse
Belief that suicide is immoral; high
Demographic risk factors
spirituality
◊ Male
Engaged in work or school
◊ Age (especially young adults and older adults)
Engaged in enjoyable activities
◊ No spouse or live-in partner
Access to health care with support of
Medical risk factors
ongoing medical and mental health
◊ Chronic illness/pain or recent change in health status
relationships
◊ Non-adherence to treatment or difficulty making treatment
• Demographic protective factors
decisions
Married, child-rearing responsibilities
◊ Sleep disorder (See SSD-1)
Employed
◊ Poor physical and emotional function, including disability
◊ Access to potentially lethal medications (opioids, BZD,
antidepressants)
aFor further information on screening and responding to suicide risk see:
https://www.healthquality.va.gov/guidelines/MH/srb/VASuicidePreventionPocketGuidePRINT508FINAL.pdf.

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ACUTE (URGENT/EMERGENT) INTERVENTIONS
Develop safety plan with survivor and family

Lower risk based on: • Immediate referral for mental health evaluation based on urgency
• Suicidal ideation with no plan, no thoughts of • Regular follow-up and monitoring until psychiatric care is in place
danger to others • Address underlying conditions and risk factors
• Clinical judgment based on assessment of • Have survivor agree to contact a health care provider, call 911, or go to
risk factors and protective factors the nearest emergency room if suicidal thoughts increase or change
• For suicide hotline information (See SURV-B)
Emergency intervention:
• Evaluate availability of firearms/weapons and arrange to have them
secured
Elevated risk of danger to self or others based on: • If offsite and threat is to others or patient is agitated or threatening:
• Suicidal or homicidal thoughts with plan Call 911
and/or with multiple other risk factors or and/or identify caregiver who is with patient to take to emergency room
• Clinical judgment based on assessment of or call 911 or follow state mental health emergency plan
risk factors and protective factors • If onsite and patient becomes agitated or threatening:
• Inability to care for self Involve other staff/security, keep door open, call 911, and maintain
direct observation of patient
Refer to emergency psychiatric evaluation procedures onsite
Identify and follow any state reporting or other requirements

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SAFETY EVALUATION ACUTE (URGENT/EMERGENT) INTERVENTIONS
DANGER FOR ABUSE OR NEGLECT

OF VULNERABLE PERSON Determine acuity, involve social work or emergency
(CHILD, ELDERLY, PERSON services, and follow mandatory reporting requirements
UNABLE TO CARE FOR SELF): • Refer to urgent social work or emergency room for
• Self-report or observation of risk for full evaluation of risks and options
or actual physical, sexual, health • Follow state laws for reporting abuse
care, or financial abuse
SUBSTANCE ABUSE/DEPENDENCE
• Self-report, caregiver/family report, or observation of See Substance-Related and Addictive Disorders (DIS-21)
misuse of medications or of altered mental status section in the NCCN Guidelines for Distress Management
potentially related to drug or alcohol use

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RISK FACTORS FOR PTSD

• Physical
Recurrence of cancer
Intensive treatment (eg, bone marrow/stem cell transplant, intensive care unit stay)
Advanced disease
Younger age
• Psychosocial
Exposure to previous trauma (eg, combat, sexual assault, major loss)
History of mental health issues prior to cancer
Poor coping skills (eg, using avoidance)
Lower income and/or less education
Less social support
• Significant change in life stressors including health, interpersonal, financial, and occupational

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PRINCIPLES OF PHARMACOLOGIC INTERVENTIONS

Special Pharmacologic Considerations for Concomitant Problems: Caveats:
• Substance abuse • Review side effects with patient, noting that some may be beneficial
Minimize use of BZD (sedation, arousal, or weight gain and appetite stimulation)
Alternatives for sedation and acute anxiety are low-dose atypical • Monitor QT interval on electrocardiogram at initiation and dose
neuroleptics (ie, olanzapine, quetiapine) or gabapentin increases with neuroleptics and citalopram
• Pain syndromes (eg, neuropathy) (See SPAIN-1) • Blood pressure should be monitored with venlafaxine and treated
SNRIs appropriately
Tricyclic antidepressants (TCAs) • Refer to specialist if first-line treatment fails or if there are
◊ Amitriptyline has sedating properties that may or may not be complicating factors such as chronic pain or substance abuse
desirable • Use psychotropics with cytochrome P450 interactions with caution
◊ Nortriptyline and desipramine have the fewest side effects in survivors taking tamoxifen
• Fatigue (See SFAT-1) Fluoxetinea
Consider less-sedating antidepressants such as bupropion Paroxetinea
Evidence for psychostimulant effects for depression and fatigue Sertralinea
are limited and mixed (See SFAT-5) Bupropion
• Insomnia Fluvoxamine
See Sleep Disorders (See SSD-1) Nefazodone
Duloxetine
Clomipramine
aSSRIs, and in particular paroxetine, block conversion of tamoxifen to active metabolites through CYP2D6.

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Survivorship Cognitive Function
COGNITIVE FUNCTION FOLLOWING CANCER TREATMENT

General Principles
• Growing evidence supports the validity of the patient-reported experience of cognitive dysfunction associated with cancer diagnosis and
treatments.
• Neuropsychological testing and brain imaging have demonstrated abnormalities in patients diagnosed with and treated for cancer.
• Currently no effective brief screening tool for cancer-associated cognitive dysfunction has been identified. Existing diagnostic tools do not
strongly correlate with patient reports of cognitive dysfunction. The Mini-Mental State Examination (MMSE®)a and similar screening tools
lack adequate sensitivity for the more subtle decline in cognitive performance most commonly seen in cancer survivors.
• There is limited evidence to guide management of this condition.
• Patients benefit from validation of their symptom experience, a thorough evaluation of this concern and related issues, and education.
• Imaging studies may not be helpful, except to rule out structural abnormalities as indicated by high-risk illness, or focal neurologic deficits
or comorbidities.
• Patients who report cognitive impairment should be screened for potentially reversible factors that may contribute to cognitive impairment
(ie, depression, sleep disturbance, fatigue).
• These guidelines address cognitive function of survivors with non-CNS malignancies who did not have CNS-directed therapies.
aFolstein MF, Folstein SE, McHugh PR. “Mini-mental state”: A practical method for grading the cognitive state of patients for the clinician.
J Psychiatr Res 1975;12:189-198.

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COGNITIVE FUNCTION ASSESSMENT SPECIALIZED EVALUATION

Focused history:
• Focal neurologic deficits
• High risk or known metastatic disease/brain primary Neuroimaging
• Onset, temporality
• Age (a risk factor for developing cognitive deficiency)
• Trajectory over time
• Cancer treatment history
• Prescription medications/OTC medications and supplements
• Education attainment
• Caregiver assessment of cognitive function
• Nature of impairments per patient; clarifying questions may include:
Do you have difficulty paying attention? Multitasking?
Do you frequently leave tasks incomplete?
Do you have difficulty finding words?
Do you have difficulty remembering things? See Cancer-Associated
Do you need to use more prompts like notes or reminders than you used to? Cognitive Dysfunction
Does it take you longer to think through problems; does your thinking seem slower? Interventions (SCF-3)
Do you notice an impact on functional performance? Job performance?
• Assessment of medical history that may impact cognitive function
Assessment of contributing factors:

• Medications/side effects
• Emotional distress
Depression/anxiety (See SANXDE-1 and
NCCN Guidelines for Distress Management)
• Symptom burden
Pain (See SPAIN-1)
Fatigue (See SFAT-1)
Sleep disturbance (See SSD-1)
• Comorbidities
• Use of alcohol and other agents that alter cognition
• New-onset vitamin deficiencies and
endocrinopathies (eg, TSH, B12)

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CANCER-ASSOCIATED COGNITIVE DYSFUNCTION INTERVENTIONS
General Strategies for Management of Cancer-

Associated Cognitive Dysfunction
• Teach enhanced organizational strategies (ie,
using memory aids like notebooks and planners,
keeping items in the same place, using reminder
notes, smart phone technology)
• Encourage patients to do the most cognitively
demanding tasks at the time of day when energy
levels are highest
• Provide information about relaxation or stress
management skills for daily use
Patient/Family Education and Counseling • Recommend routine physical activity (See HL-1)
• Validation of experience of cognitive dysfunction • Recommend limiting use of alcohol and other
associated with cancer diagnosis and treatment agents that alter cognition and sleep
See Specific Interventions
• Reassurance that cancer-associated cognitive • Consider meditation, yoga, mindfulness-based
(SCF-4)
dysfunction is often not a progressive neurologic stress reduction, and cognitive training (ie, brain
disorder like progressive dementiasb games)
• Support self-management and coping strategies • For older adults also see the cognitive function
section of the NCCN Guidelines for Older Adult
Oncology (OAO-F)
• Optimize management of:
Depression or emotional distress
(See appropriate survivorship guidelines or
NCCN Guidelines for Distress Management)
Contributing symptoms such as pain
(See SPAIN-1)
Medical comorbidities
bCognitive dysfunction may be progressive in survivors of CNS cancers or those who had CNS-directed therapies.

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CANCER-ASSOCIATED COGNITIVE DYSFUNCTION SPECIFIC INTERVENTIONS

FIRST-LINE INTERVENTIONS SECOND-LINE INTERVENTIONS
• Neuropsychological evaluation and recommendationsc

• Cognitive rehabilitation
Occupational therapyd Consider trial use of medications
Speech therapy (methylphenidate, modafinil, or donepezil)e
Neuropsychologist
• Psychotherapy
• Recommend routine physical activity (See HL-1)
cNeuropsychological evaluation and intervention may be therapeutic and validating. Evaluation may also be necessary if an individual is pursuing disability benefits and
cognitive impairment is a contributing factor to work limitation.
dOccupational therapy strategies focus on improvement of cognitive functioning and may be most effective for an individual who notes the impact of specific functional
limitations (ie, word finding, comprehension or task completion, quality-of-life or role expectations).
eOverall the evidence for these medications is lacking, but there may be some benefit in select survivors or certain clinical scenarios.

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Survivorship Fatigue
DEFINITION OF CANCER-RELATED FATIGUE
• Cancer-related fatigue is a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related
to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning.a
CONSIDERATIONS FOR FATIGUE IN CANCER SURVIVORS
• Fatigue is a common complaint in individuals undergoing cancer therapy and can be a persistent problem for some cancer survivors in the
months and years after cancer diagnosis.
Receipt of chemotherapy and radiation are both predisposing factors for cancer-related fatigue, but it can be seen in some patients who
are treated with surgery alone.
The time-course of fatigue is unique to the survivor and his or her treatment plan, but some general principles apply. Mild to moderate
fatigue is common in cancer survivors who undergo chemotherapy and/or radiation; mild to moderate fatigue lasting up to one year can
occur in a proportion of cancer survivors.
Fatigue that initially presents months after the completion of adjuvant therapy or fatigue that worsens over this period warrants additional
evaluation.
aSee the NCCN Guidelines for Cancer-Related Fatigue.

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SCREENING
None to mild (0–3)b Ongoing reevaluation

Screen every patient for fatigue as
vital sign at regular intervalsb
• Severity: 0–10 scalec
(0=No fatigue;
10=Worst fatigue you can imagine)
or
None, mild, moderate, severe
Moderate (4–6)b
See Primary Evaluation (SFAT-3)
or Severe (7–10)b
bRecommended screen and re-evaluation: “How would you rate your fatigue on a scale of 0 –10 over the past 7 days?”
cButt Z, Wagner LI, Beaumont JL, et al. Use of a
single-item screening tool to detect clinically significant fatigue, pain, distress, and anorexia in ambulatory cancer
practice. J Pain Symptom Manage 2008;35:20-30.

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PRIMARY EVALUATION FATIGUE SCORE: EVALUATION

MODERATE OR SEVERE (4–10)
H&P:
• Focused fatigue history
Onset, pattern, duration
Change over time
Associated or alleviating factors Laboratory Evaluation:
Interference with function • Consider performing laboratory
• Evaluate disease status evaluation based on presence
Other Diagnostic Testing:
Evaluate risk of recurrence based on stage, of other symptoms, onset, and
• Consider radiologic
pathologic factors, and treatment history severity of fatigue
assessment only if high
Perform review of systems to determine if other CBC with differential
risk of disease recurrence
symptoms substantiate suspicion for recurrence ◊ Compare end-of-treatment
OR if accompanying signs
• Assessment of treatable contributing factors: hemoglobin/hematocrit with
and symptoms suggest
Comorbidities current values
presence of metastatic
◊ Alcohol/substance abuse ◊ Assess other cell lines (WBC
disease
◊ Cardiac dysfunction and platelets)
• Consider cardiac
◊ Endocrine dysfunction (eg, hypothyroidism, Comprehensive metabolic panel
testing (ECHO) for
hypogonadism, adrenal insufficiency) ◊ Assess electrolytes See Treatment
patients treated with
◊ Gastrointestinal dysfunction ◊ Assess hepatic and renal of Contributing
an anthracycline
◊ Hepatic dysfunction function Factors (SFAT-4)
(See SCARDIO-1),
◊ Infection Endocrine evaluation
trastuzumab,
◊ Pulmonary dysfunction ◊ TSH, especially in patients
bevacizumab, other
◊ Renal dysfunction who have received prior
VEGF- or HER2-targeted
◊ Anemia head/neck, torso, or breast
therapy, or other therapy
◊ Arthritis radiation
known to cause cardiac
Prescribed or OTC medications ◊ Consider more
dysfunction
(eg, sleep aids, pain medications, antiemetics) comprehensive evaluation or
• Chest x-ray and oxygen
Emotional distress- screen for anxiety and referral to specialist if other
saturation testing for
depression (See SANXDE-1) symptoms present
pulmonary complaintsd
Sleep disturbance (eg, insomnia, sleep apnea, ◊ Cortisol stimulation test, if
vasomotor symptoms, restless legs syndrome history of prolonged steroid
[RLS]) (See SSD-1) use
Pain (See SPAIN-1)
Nutritional issues
◊ Weight/caloric intake changes (See SNWM-1)
Deconditioning/loss of muscle mass
dRefer to a pulmonologist for pulmonary complaints.

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TREATMENT OF CONTRIBUTING FACTORS
• Treat contributing factors:

Medications/side effects
Pain (See SPAIN-1)
Emotional distress (See SANXDE-1) and NCCN Guidelines for
Distress Management
Anemia See Interventions for Cancer Survivors (SFAT-5)
◊ Treat iron, B12, folate deficiency, if present
◊ Consider referral/further evaluation for anemia or cytopenias
Nutritional deficit/imbalance
Comorbidities

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INTERVENTIONS FOR CANCER SURVIVORS

Patient/Family Education Physical Activity Other Interventionse Pharmacologich
and Counseling
• Psychosocial interventions
• Maintain adequate levels of physical activity
(category 1)
(category 1) (See SPA-1 and SPA-4)
CBTf/Behavioral therapy
• Survivors at higher risk of injury (eg, those living
Provide information (category 1)
with neuropathy, cardiomyopathy, lymphedema,
about patterns of Mindfulness-based stress
or other long-term effects of therapy or other
fatigue during and reduction (category 1)
comorbidities) should be referred to a physical Consider
after treatment Psycho-educational
therapist or exercise specialist psychostimulantsi
• Self-monitoring of therapies/Educational
• Make use of local resources to help patients (methylphenidatej)
fatigue levels therapies (category 1)
increase exercise after ruling out other
• Energy conservation Supportive expressive
(eg, aerobics, strength training, yoga) causes of fatigue
Set priorities therapies (category 1)g
Community exercise programs or classes, and failure of other
Pace • Nutrition consultation
preferably those focused on cancer survivors interventions
Schedule activities • CBTf for sleep
Exercise professional certified by the American
at times of peak (category 1) (See SSD-1)
College of Sports Medicine
energy Stimulus control
For patients with fatigue interfering with
Sleep restriction
function, consider referral to a physical
Sleep hygiene
therapist or physiatrist
• Acupuncture
eInterventions should be culturally specific and tailored to the needs of patients and families along the illness trajectory, because not all patients may be able to integrate
these options due to variances in individual circumstances and resources.
fA type of psychotherapy that focuses on recognizing and changing maladaptive thoughts and behaviors to reduce negative emotions and facilitate psychological
adjustment.
gSupportive expressive therapies (such as support groups, counseling, and journal writing) facilitate expression of emotion and foster support from one or more people.
hPharmacologic interventions remain investigational, but have been reported to improve symptoms of fatigue in some patients.
iPsychostimulants are at times used to treat cancer-related fatigue. A number of studies have evaluated their efficacy in the setting of active treatment and results have
been mixed. There are extremely limited data regarding the use of these agents in the post-treatment setting.
jMethylphenidate should be used cautiously and should not be used until treatment- and disease-specific morbidities have been characterized or excluded. Optimal
dosing and schedule have not been established for use of psychostimulants in patients with cancer.

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Survivorship Lymphedema
DEFINITION AND STAGES OF LYMPHEDEMAa,b

• Definition: Lymphedema occurs when lymph fluid accumulates in the interstitial tissue, causing swelling of the limb or other areas such as
the neck, trunk, or genitals. It is a common side effect of cancer treatment, occurring on the same side of the body as the cancer treatment,
as a result of dysfunction of the lymphatic system.
• Stage 0 (latent/subclinical): Lymphatic dysfunction without swelling; subtle symptoms, such as a feeling of heaviness or fatigue in the limb,
may be present.
• Stage 1 (spontaneously reversible): Accumulation of fluid and protein causing swelling; pitting edema may be evident; increased girth,
heaviness, and/or stiffness of affected area. For the limbs, swelling is relieved with elevation.
• Stage 2 (irreversible): Spongy tissue consistency, with pitting edema that becomes less evident as swelling increases; tissue fibrosis
causing hardness and increase in size. For the limbs, swelling is not relieved with elevation.
• Stage 3 (lymphostatic elephantiasis): Severe dry, scaly, thickened skin; increased swelling and girth of affected area; can be debilitating. In
the limbs, fluid leakage and blisters are common.
aNational Cancer Institute Lymphedema (PDQ®)–Health Professional Version. https://www.cancer.gov/about-cancer/treatment/side-effects/lymphedema/lymphedema-

hp-pdq.
bInternational Society of Lymphology. The diagnosis and treatment of peripheral lymphedema: 2013 Consensus Document of the International Society of Lymphology.
Lymphology 2013;46:1-11. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23930436.

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PRINCIPLES OF LYMPHEDEMA
• Lymphedema is a potential side effect after the treatment of cancer resulting from damage to the lymphatic system. Lymphedema is most
often diagnosed within 18 months of treatment; however, it can develop anytime in the life of the survivor. Depending on stage of diagnosis,
lymphedema can be an acute or chronic condition.
• Swelling on the same side as the cancer treatment is a universal symptom of lymphedema. Additional initial symptoms may include
sensation of heaviness, fatigue, fullness or tightness in the skin, or pain. Symptoms including decreased range of motion or strength and
thickening of the skin may occur in later stages.a
• Survivors who had surgery or radiation to the axillary, supraclavicular, cervical, or inguinal lymph node system are at risk for the
development of lymphedema. Sentinel node biopsy also increases the risk of lymphedema, although it poses less risk than complete
dissection or radiation to the nodal group.
• Obesity (BMI >30 kg/m2), localized infection, increased number of nodes removed, and higher initial extent of disease raise the risk of
lymphedema development.
• Pretreatment limb measurement of both sides should be performed as a baseline for survivors with treatment-related or individual risk
factors, preferably by a trained lymphedema specialist.
• Early detection/diagnosis is key for optimal lymphedema management because stages 0 and 1 are reversible, whereas stages 2 and 3 are
less responsive to treatment. Therefore, survivors should be told to inform their medical provider if subtle swelling or any other symptoms
(eg, fullness, tightness, heaviness, pain) on the treated side are noted.
• Lymphedema may cause or exacerbate psychological distress (See SANXDE-1).
• Survivors at risk for lymphedema and those with lymphedema are at a higher risk of localized infection in the affected area. These infections
can require hospitalization for IV antibiotics. Therefore, survivors with or at risk for lymphedema should be educated to inform their medical
provider immediately for signs of infection in the affected area.
• Progressive weight training under supervision and physical activity are not associated with exacerbation or development of
lymphedema.c,d,e
• Observational studies have demonstrated that air travel, venipuncture, and blood pressure measurement (via arm cuff) are not associated
with exacerbation or development of lymphedema, and precautionary measures are likely unnecessary.f,g In the absence of high-level data,
however, the panel recommends that medical procedures such as venipuncture and blood pressure measurements be done on the non–at-
risk arm/limb if possible.h If necessary, procedures may be done using the at-risk arm/limb. More research is needed to determine the effect
of these procedures on the risk of lymphedema.
aNational Cancer Institute Lymphedema (PDQ®)–Health Professional Version https://www.cancer.gov/about-cancer/treatment/side-effects/lymphedema/lymphedema-
hp-pdq.
cSchmitz KH, Courneya KS, Matthews C, et al. American College of Sports Medicine. American College of Sports Medicine roundtable on exercise guidelines for cancer
survivors. Med Sci Sports Exerc 2010;42:1409-1426.
dIrwin M, ed. ACSM's Guide to Exercise and Cancer Survivorship. Champaign, IL: The American College of Sports Medicine; 2012.
eNational Lymphedema Network. Position Paper: Exercise 2013. https://issuu.com/lymphnet/docs/exercise.
fAsdourian MS, Skolny MN, Brunelle C, et al. Precautions for breast cancer-related lymphoedema: risk from air travel, ipsilateral arm blood pressure measurements,
skin puncture, extreme temperatures, and cellulitis. Lancet Oncol 2016;17:e392-405.
gAhn S, Port ER. Lymphedema precautions: Time to abandon old practices? J Clin Oncol 2016;34:655-658.
hNational Lymphedema Network. Position Paper: Lymphedema Risk Reduction Practices 2012 https://issuu.com/lymphnet/docs/risk_reduction.

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SURVIVOR AT RISK SYMPTOM WORKUP IF LYMPHEDEMA TREATMENT

FOR LYMPHEDEMA ASSESSMENT IS SUSPECTED
• Survivor lymphedema
• Rule out recurrence of cancer education, including self-
Inquire at each visit Surveillance
• Refer to a certified care management
about: (See
lymphedema therapist (See SLYMPH-A)
• Frequency SLYMPH-4)
(if available)i for assessments • Refer to certified
and severity of or
such as: lymphedema therapist (if
swelling If no
Subjective symptoms/signs available)i for consideration
• Swelling that response, but
Limb volume measurementj of the following:
interferes with persistent
Symptoms Clinical examination, which Compression garmentsk
daily activities symptoms,
present may include, but is not ◊ Review fit of garments
• Pain/discomfort consider
limited to range of motion, ◊ Review use of garments
• Range of motion reviewing
muscle performance, Progressive resistance
and mobility adherance
circulation, sensation, training under
(ie, bending, to treatment
hemodynamic monitoring, supervisionl,m
Inquire stretching, plan and/
and functional mobility Manual lymphatic
about flexibility) or self care
• Assess distress drainagei,n
swelling or • Strength management
(See SANXDE-1) • Refer to physical therapy for
feeling of range-of-motion exercises
heaviness,
fatigue, or
fullness
Symptoms Re-evaluate and inquire about

not present symptoms at each visit
iCertified lymphedema therapists can be located using the following resource: https://www.clt-lana.org/search/therapists/.
jIf baseline measurement is not available, measure unaffected contralateral limb as a reference.
kCompression garments should be prescribed. Optimally, they should be fitted and measured by a certified lymphedema therapist.
lIf a certified therapist is not available, survivors with lymphedema can perform resistance training with a professional trainer who has knowledge of cancer-related
physical activity principles. Weights should be slowly progressed as tolerated, and lymphedema should be evaluated periodically.
mSee Principles of Physical Activity for Survivors with or At Risk for Lymphedema (SLYMPH-B).
nIf a certified lymphedema therapist is not available, consider referral to appropriate provider for treatment.

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SURVEILLANCE
• Inquire about fit and age of compression garments

• Replace compression garments as clinically indicated
• Check range of motion
Follow-up with treatment
• Inquire about performance of prescribed exercises
team as clinically
• Inquire about self-care management
indicated
• Continue survivor lymphedema education (See SLYMPH-A)
• Continue treatment as clinically indicated (See SLYMPH-3)
• Assess for distress (See SANXDE-1)

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SURVIVOR LYMPHEDEMA EDUCATION

• Survivors should be educated regarding:
Signs and symptoms of lymphedema and the importance of rapid reporting to the treatment team.
Signs and symptoms of infection (eg, redness, pain, skin streaking/warm to touch) in the affected area and the importance of rapid
reporting to the treatment team.
Self-care management: Infection prevention measures,a risk reduction strategies,b maintenance of skin integrity on the affected side
• Survivors should also be informed that:
Progressive weight training under supervision and physical activity are not associated with exacerbation or development of
lymphedema.1,2,3 (See SLYMPH-B)
◊ Progressive resistance training under supervision may improve lymphedema symptoms. However, caution is advised in this population,
and survivors with or at risk for lymphedema should discuss physical activity plans with a lymphedema specialist before starting a
program that involves strength or resistance training. (See SLYMPH-B)
◊ Water exercise under supervision may be an option to consider after assessing any skin integrity and/or incision issues.4
Studies have demonstrated that air travel, venipuncture, and blood pressure measurement (via arm cuff) are not associated with
exacerbation or development of lymphedema, and precautionary measures are likely unnecessary.5,6 However, medical procedures such as
venipuncture and blood pressure measurements should be done on the non–at-risk arm/limb if possible.7 If necessary, procedures may be
done using the at-risk arm/limb.
Footnotes
aRisk of infections can be reduced by safe pet care and gardening techniques (See SIMIN-2).
bFor a complete list of lymphedema risk reduction practices, see the Position Statement from the National Lymphedema Network:
https://issuu.com/lymphnet/docs/risk_reduction.
References
1Schmitz KH, Courneya KS, Matthews C, et al. American College of Sports Medicine. American College of Sports Medicine roundtable on exercise guidelines for cancer
survivors. Med Sci Sports Exerc 2010;42:1409-1426.
2Irwin M, ed. ACSM's Guide to Exercise and Cancer Survivorship. Champaign, IL: The American College of Sports Medicine; 2012.
3National Lymphedema Network. Position Paper: Exercise 2013. https://issuu.com/lymphnet/docs/exercise.
4Lindquist H, Enblom A. Water exercise compared to land exercise or standard care in female cancer survivors with secondary lymphedema. Lymphology 2015;48:64-
79.
5Asdourian MS, Skolny MN, Brunelle C, et al. Precautions for breast cancer-related lymphoedema: risk from air travel, ipsilateral arm blood pressure measurements,
skin puncture, extreme temperatures, and cellulitis. Lancet Oncol 2016;17:e392-405.
6Ahn S, Port ER. Lymphedema precautions: Time to abandon old practices? J Clin Oncol 2016;34:655-658.
7National Lymphedema Network. Position Paper: Lymphedema Risk Reduction Practices 2012 https://issuu.com/lymphnet/docs/risk_reduction.

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PRINCIPLES OF PHYSICAL ACTIVITY FOR SURVIVORS WITH OR AT RISK FOR LYMPHEDEMA

• Lymphedema is not a contraindication for physical activity, and no special precautions are required if participating in cardiovascular/aerobic
exercise or strength training of unaffected limbs.
• Continued full use of the extremity and range-of-motion exercises are encouraged to maintain strength and range of motion even in the
presence of lymphedema.
• Progressive strength training:
Gradually increase resistance by smallest increment possible with monitoring.
Consider referral to lymphedema specialist for evaluation prior to starting a physical activity program that involves the affected or at-risk
limb.
Compression garments may be required during training sessions.
When possible, survivors should work with trained exercise professionals1 and initiate exercises involving affected body part only if
lymphedema specialist or other appropriate health care provider determines that lymphedema is stable. Factors that may be considered
include:
◊ No need for lymphedema therapy within past 3 months
◊ No recent limb infections requiring antibiotics
◊ No change in limb circumference >10%
◊ No change in ability to perform activities of daily living
• Survivors should undergo baseline and periodic evaluation for development or exacerbation of lymphedema.
• Survivors should stop exercise and see a lymphedema specialist if exacerbation of lymphedema occurs.
1Trained personnel can include physical and occupational therapists, certified exercise professionals, and rehabilitation specialists. Specialized training in working with
survivors is available for both physical therapists and exercise professionals (American College of Sports Medicine [ACSM] [http://www.acsm.org/get-stay-certified] or

SLYMPH-B

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Survivorship Hormone-Related Symptoms (Female)
PRINCIPLES OF MENOPAUSE MANAGEMENT IN FEMALE SURVIVORS

Menopause
• Menopause is defined as no menses for one year in the absence of prior chemotherapy or tamoxifen use, or no menses after surgical
removal of all ovarian tissue.
• Many survivors may experience symptoms without meeting the definition of menopause.
• In female survivors with prior chemotherapy or pelvic radiation exposure or survivors on tamoxifen, serial estradiol levels may be useful to
confirm post-menopausal status.
• In non-cancer populations, primary ovarian insufficiency or early menopause may be associated with specific menopause-related health
risks (see below). There are limited data in cancer survivors.
• Peri- or pre-menopausal survivors
For survivors who have become amenorrheic and later develop bleeding, serial estradiol levels can be useful to determine return of
ovarian function. Other markers including follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), and inhibin may provide
additional information on ovarian status in female cancer survivors with prior chemotherapy or those on tamoxifen, but alone are not
reliable to ensure menopausal status.
Survivors who have become amenorrheic and are sexually active should be counseled on the need for contraception to prevent
unintended pregnancy if they do not meet the definition of menopause.
Menopausal Signs and Symptoms Menopause-Related Health Risks
• Vasomotor symptoms (ie, hot flashes/night sweats) • Osteoporosis/bone fractures
• Vaginal dryness • Cardiovascular disease
• Urogenital complaints • Cognitive change
• Sexual dysfunction • Parkinson's disease
• Mood disturbance and depression
• Cognitive dysfunction
• Arthralgias/myalgias
• Fatigue
Treatment Options for Vasomotor Symptoms (See SMP-4)
• Non-hormonal options • Hormonal therapies (contraindicated in survivors of hormonally mediated cancers;
Prescription alternatives (See SMP-A) use with caution in those with increased genetic cancer risk) (See SMP-B)
OTC options Combination estrogen and progestins (for survivors with an intact uterus) or
Integrative therapies estrogen alone (for survivors without a uterus)
Lifestyle modifications (See HL-1) Tissue selective estrogen complexes (TSECs)a
Custom-compounded bioidentical hormone therapy (contraindicated in survivors
of hormonally mediated cancers; use with caution in those with increased genetic
cancer risk) (See SMP-B)
aNovel therapies that combine a selective estrogen receptor modulator (SERM) with estrogen creating a tissue selective estrogen complex (TSEC).
SMP-1

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Survivorship Hormone-Related Symptoms (Male)
PRINCIPLES OF MANAGEMENT OF HORMONAL SYMPTOMS IN MALE SURVIVORS

• Male survivors who have received radiation therapy, chemotherapy, or surgery for non-prostate malignancies may have hypogonadism and should
be evaluated for biochemical evidence of hypogonadism (ie, testosterone free and total, LH, prolactin) and treated with testosterone for menopausal
symptoms.
• Male survivors of prostate cancer who have no evidence of recurrent disease may have symptoms of hypogonadism or have prior history of
hypogonadism. These patients should be evaluated for biochemical evidence of hypogonadism. When to initiate treatment for low testosterone in
prostate cancer survivors or resume treatments for men who had pre-existing hypogonadism is controversial and should be coordinated with the
patient’s primary cancer physician (ie, surgeon, oncologist, radiation oncologist).
• Androgen deprivation therapy (ADT) is the main therapeutic approach to metastatic prostate cancer, and may be used as adjuvant or neoadjuvant
therapy in the treatment of prostate cancer.
• Male survivors who are receiving ADT may experience menopausal symptoms and sexual dysfunction. These patients should not receive androgens (eg,
testosterone).
• ADT-related symptoms and health risks:
Acute kidney injury Fatigue
Anemia Gynecomastia
Arthralgias/myalgias Osteoporosis/bone fractures
Cardiovascular diseaseb Sexual dysfunctionc
◊ Prolongation of QT/QTc interval Sleep disturbance
Cognitive dysfunction Testicle atrophy
Decreased muscle (sarcopenia) and increased body fat Thinning body haird
Decreased penile size Vasomotor symptoms (ie, hot flashes/night sweats)e
Mood disturbance and depression Venous thromboembolic disease
Diabetes mellitus (new onset)
◊ Reduced insulin sensitivity
Treatment Options for Vasomotor Symptoms (See SMP-6)

• Non-hormonal options • Hormonal therapies (contraindicated in survivors of hormonally
Prescription alternatives (See SMP-A) mediated cancers; use with caution in those with increased genetic
OTC options cancer risk)
Integrative therapies Androgens (eg, testosterone)
Lifestyle modifications (See HL-1) ◊ Contraindicated in males with carcinoma of the breast or known
or suspected prostate cancer
Medroxyprogesterone acetate (a progestin)
Cyproterone acetate (an antiandrogen)
Estrogen (eg, diethylstilbestrol)
bIn males, ADT may increase cardiovascular morbidity and mortality, notably in the first 6 months of therapy and in men with two or more prior cardiovascular events. An
increase in serum LDL cholesterol, HDL cholesterol, and triglycerides may also be seen.
cADT-related sexual dysfunction includes loss of libido, loss of nocturnal and morning erections, and varying degrees of erectile dysfunction.
dAlthough facial and body hair decrease, some bald men may have some regrowth of scalp hair.
eHot flashes may be associated with nausea and sweating and may occur during sleep.

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Survivorship: Hormone-Related Symptoms (Females and Males) Discussion
SCREENING WORKUP/ TREATMENT

ASSESSMENT
• H&P
• Rule out other causes of
menopausal symptoms • Females
(ie, thyroid disease, Vasomotor symptoms (ie, hot flashes/night sweats)
diabetes) (See SMP-4)
• In females assess serial Vaginal dryness and/or urogenital complaints
estradiol levels as (See SMP-5)
clinically indicatedf • Males
• In males assess morning Vasomotor symptoms (See SMP-6)
Symptoms
total testosterone and Gynecomastia (See SMP-6)
disruptive to
free testosterone as Anemiag
quality of life
clinically indicated • Males and Females
present
• Assess FSH, LH, and Sexual dysfunction (See SSF-1)
prolactin levels as Lack of sexual desire (See SSF-1)
clinically indicated Sleep disturbance (See SSD-1)
• For vaginal dryness, Mood disturbance and depression (See SANXDE-1)
Screen for menopausal consider pelvic Cognitive dysfunction (See SCF-1)
symptoms disruptive to evaluation to assess Arthralgias/myalgias (See SPAIN-6)
quality of life at regular for vaginal atrophy or Fatigue (See SFAT-1)
intervals referral to appropriate
(See SMP-1 and SMP-2) specialist
No symptoms
disruptive to
Rescreen at subsequent visits
quality of life
present
fForperi- or pre-menopausal female survivors who have become amenorrheic and later develop bleeding, serial estradiol levels can be useful to determine return of
ovarian function. Other markers including follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), and inhibin may provide additional information on ovarian
status in female cancer survivors with prior chemotherapy or those on tamoxifen, but alone are not reliable to ensure menopausal status.
gADT-associated anemia is generally responsive to blood transfusions and erythropoietin and should be treated as per the NCCN Guidelines for Hematopoietic Growth
Factors.

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MENOPAUSE SYMPTOM TREATMENT
• Non-hormonal pharmacologic treatmentsh

Categories include antidepressants,i anti-convulsants, neuropathic pain relievers, and
certain anti-hypertensives
• Non-pharmacologic treatmentsj
Vasomotor symptoms Acupuncture
(ie, hot flashes/night Exercise/physical activity (See SPA-1)
sweats) disruptive to Lifestyle modificationsk (See HL-1)
quality of life in females
Weight loss if overweight or obese (See SNWM-1)
Integrative therapies including CBT, yoga, and hypnosis
• Menopausal hormone therapy (MHT) or other hormonal therapies in appropriate
candidatesl,m with referral to appropriate specialist for MHT dosing and management
jCompounds with limited evidence of safety and efficacy

Phytoestrogens
Botanicals
Dietary supplements
• Limited data show a possible benefit of black cohosh for vasomotor symptoms in the general population; however, randomized
data in breast cancer survivors show no benefit (www.ncbi.nlm.nih.gov/pubmed/16782922). There is concern about potential liver
toxicity with long-term use of black cohosh.
• Data are limited on the effectiveness and safety of these nonpharmacologic treatments in survivors of some cancers. The panel
consensus is that the efficacy and safety data for these treatments are too limited to make a recommendation for use.
hSee Non-Hormonal Pharmacologic Treatments and Dosing (SMP-A).
iLower doses of antidepressants are often effective if the intent is to treat hot flashes (See SMP-A).
kDrinking alcohol may cause hot flashes in males/females. Individual responses to alcohol may vary. If alcohol is a trigger, consider limiting intake.
lSee Principles of Menopausal Hormone Therapy (MHT) Use In Survivors (Females) (SMP-B).
mMHT is contraindicated in survivors of hormonally mediated cancers.

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MENOPAUSE SYMPTOM TREATMENT
• Non-hormonal treatments
Vaginal moisturizers, vaginal gels, oils (category 2B)
• Lubricants for sexual activityn
• Local estrogen treatmento (ie, rings, suppositories, creams) (category 2B)
Limited data in breast cancer survivors suggest minimal systemic absorption
Vaginal dryness
with rings and suppositories. Therefore, if estrogen-based treatment is warranted,
rings and suppositories are preferred over creams for survivors of hormonally
sensitive tumors.
• Other topical hormones (ie, testosterone,p DHEAo,q)
• Consider referral to appropriate specialist for management
• For vaginal pain or discomfort, see SSF-2
• Local estrogen treatmento

Urogenital complaints (females)
• Referral to appropriate specialist for management
nSurvivors should be cautioned that some lubricants may be irritating to the area of application.
oVaginal estrogen and vaginal testosterone preparations can be used in managing vaginal atrophy,but safety has not been established for use in patients with or
survivors of estrogen-dependent cancers.
pAlthough compounded testosterone vaginal creams are often used, there is a lack of data showing efficacy or safety in cancer survivors.
qDHEA should be used with caution in survivors with a history of estrogen-dependent cancers.

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Survivorship Hormone-Related Symptoms (Male)
ADT-RELATED SYMPTOMS TREATMENT

• Modification to ADT (See NCCN Guidelines for Prostate Cancer)
• Pharmacologic treatments
Hormonal therapy in appropriate candidatesr with referral to appropriate specialist
for dosing and management
◊ Medroxyprogesterone
◊ Cyproterone acetate
Vasomotor symptoms ◊ Estrogen (eg, diethylstilbestrol)
(ie, hot flashes/night Non-hormonal therapiesi
sweats) disruptive to ◊ Venlafaxine
quality of life in males ◊ Gabapentin
• Non-pharmacologic treatmentss
Acupuncture
Exercise/physical activity (See SPA-1)
Lifestyle modificationsj (See HL-1)
Cognitive behavior therapy
Weight loss if overweight or obese (See SNWM-1)
• Prophylactic radiation (must be delivered prior to development of breast tissues)

Gynecomastia • Tamoxifen
• Reduction mammoplasty
sCompounds with limited evidence of safety and efficacy

Phytoestrogens
Botanicals
Vitamin E
Dietary supplements
• Data are limited on the effectiveness and safety of these nonpharmacologic treatments in
survivors of some cancers. The panel consensus is that the efficacy and safety data for these
treatments are too limited to make a recommendation for use.
iSee Non-Hormonal Pharmacologic Treatments and Dosing (SMP-A).

kDrinking alcohol may cause hot flashes in males/females. Individual responses to alcohol may vary. If alcohol is a trigger, consider limiting intake.
rTestosterone is contraindicated in males with carcinoma of the breast or known or suspected prostate cancer.

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Survivorship: Hormone-Related Symptoms (Females and Males) Discussion
NON-HORMONAL PHARMACOLOGIC TREATMENTS AND DOSINGa
Class Drug Commonly Used Daily Dose for Comments

Managment of Vasomotor Symptoms (For maximum benefit, may increase to higher doses after a week as
tolerated)
Antidepressantsb Venlafaxinec 75 mg Start at lowest dose possible (25 mg or 37.5 mg) and increase as
(SNRI) tolerated
(preferred)
Desvenlafaxine 100 mg Start at lowest dose possible (25 mg or 50 mg) and increase as
(SNRI) tolerated
Escitalopram 20 mg • Start at lowest dose possible (10 mg) and increase as tolerated
(SSRI)
Citalopram 20 mg • Start at lowest dose possible (10 mg) and increase as tolerated
(SSRI)
Sertraline 50 mg • Start at lowest dose possible (25 mg) and increase as tolerated
(SSRI)d • Limited data on effectiveness
• Use with caution for survivors on tamoxifen
Paroxetine Low-dose 7.5 mg • Low-dose (7.5 mg) paroxetine is the only FDA-approved alternative to
(SSRI)d or hormones for hot flashes
Standard paroxetine short acting up to • Use with caution for survivors on tamoxifen
20 mg, controlled release up to 25 mg
Fluoxetine 20 mg • Start at lowest dose possible (10 mg) and increase as tolerated
(SSRI)d • Limited data on effectiveness
• Use with caution for survivors on tamoxifen
Anti-convulsant Gabapentinc 900 mg • Start at lowest dose possible (100 mg or 300 mg) and increase as
(preferred) (typically 300 mg 3 times a day) tolerated
• Consider starting at night time as this drug tends to cause sedation
Pregabalin 150–300 mg Start at lowest dose possible (25 mg) and increase as tolerated
Alpha-agonist Clonidine 0.1 mg Transdermal preparations may have fewer side effects
hypertensive (oral or transdermal)
aFor long-term care or maintenance and/or if lack of response, consider referral to
appropriate health care specialist. A gradual tapering of dose rather than an abrupt cVenlafaxine and gabapentin have been studied for the treatment of menopause symptoms
discontinuation of drug is recommended when discontinuing these treatments. in males, but data are limited. The other therapies have been used but not tested in males.
bAnticipated clinical response of SSRIs/SNRIs for menopausal symptoms tends to be more dSSRIs and in particular paroxetine block conversion of tamoxifen to active metabolites
rapid than the typical response for depression. through CYP2D6.

SMP-A

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PRINCIPLES OF MENOPAUSAL HORMONE THERAPY (MHT) USE IN SURVIVORS (FEMALES)

• MHT is the most effective therapy for management of vasomotor symptoms.
• General recommendations are to use the lowest dose possible to control symptoms.
Combination estrogen and progestins (for survivors with an intact uterus) or estrogen alone (for survivors without a uterus)
◊ Formulations of hormones include oral, transdermal, vaginal ring, and intrauterine device.
The TSEC conjugated estrogens/bazedoxifene is FDA approved for treating menopausal symptoms in healthy post-menopausal women.
◊ These drugs are contraindicated in survivors of hormonally dependent cancers.
Custom-compounded bioidentical hormone therapy
◊ There is a lack of data supporting claims that custom-compounded bioidentical hormones are a safer and more effective alternative to
standard hormone therapies. In fact, they may be harmful.
• If MHT is used, refer to appropriate specialist for MHT dosing and management.
• For young cancer survivors experiencing menopause at an early age, consider oral contraceptives or MHT for symptom relief and potential
cardiac and bone benefits as long as not contraindicated.
• Contraindications for MHT in cancer survivors mirror those for the general population and include:
History of hormonally mediated cancers
History of abnormal vaginal bleeding
Active or recent history of thromboembolic event
Pregnancy
Active liver disease
• Caution in:
Survivors with coronary heart disease or hypertension
Survivors at increased genetic risk for cancers
Current smokers, especially if older than 35 years
• Approach to treatment should be individualized based on risks and benefits.

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Survivorship Pain
GENERAL PRINCIPLES OF PAIN MANAGEMENT

• Comprehensive pain assessment should be done to determine the etiology of the pain.
If the pain is new and acute, differential diagnosis should include cancer recurrence.
If the pain is chronic, a specific cancer pain syndrome should be identified if possible.
• Conduct a discussion with the patient and family regarding realistic treatment goals, including improvement in functionality as well as pain
relief.
• Opioid treatment is sometimes necessary, and the lowest appropriate dose should be used for the shortest amount of time, if possible.
Adjuvant medications should be used in addition to the opioids if indicated.
• Non-opioids are appropriate as primary therapy for many pain syndromes.
• Non-pharmacologic interventions can be used as the sole treatment for pain, or as adjuncts to pharmacologic therapy.
• Physical modalities (heat, cold, massage, physical therapy, or occupational therapy) are useful and should be considered for some pain
syndromes.
• Use a multimodality approach to pain management if warranted, and if those resources are available.
• Psychological support of the survivor with chronic pain is necessary, and referral to psychosocial services should be considered for
survivors in distress. (See SANXDE-1)
• Consider referral to a specialist for patients who might benefit from further pain interventions. This could include referral to interventional
pain, physical medicine and rehabilitation, palliative care, urology, gynecology, orthopedic surgery, gastroenterology, or other appropriate
consultants.
• The panel acknowledges the legalization of medical marijuana for various conditions in multiple states. However, there are presently not
enough data to make any guideline recommendations regarding use in cancer survivors.
• Also see the NCCN Guidelines for Adult Cancer Pain.

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Survivorship Pain
PRINCIPLES OF OPIOID USE IN LONG-TERM SURVIVORS

• When opioids are appropriate and necessary, establish treatment goals with survivors and caregivers and use the lowest effective opioid
dose for the shortest period of time possible.
• Functional outcomes are important measures for patients on opioid therapy. The expected outcome (ie, improvement in function and/or
pain) should be clearly discussed with survivors and caregivers, agreed upon, and documented upon initiation and continuation of chronic
therapy.
• Re-evaluate the effectiveness and necessity of opioids on a regular basis.
If the expected outcome is not achieved, other treatment alternatives should be considered. If opioids are no longer appropriate,
recommend gradual tapering of opioids to help avoid symptoms of withdrawal.
Discussion of gradual tapering should be routine.
• Consider establishing pain treatment agreements (See PAIN-L of the NCCN Guidelines for Adult Cancer Pain).
• Address medical-related issues due to chronic or high-dose opioids.
Endocrine/hypopituitary abnormalities
◊ Testosterone deficiency
Management of opioid adverse effects (ie, constipation, nausea, pruritus, delirium, motor and cognitive impairment, respiratory depression,
sedation) (See PAIN-F of the NCCN Guidelines for Adult Cancer Pain)
• Monitor for aberrant drug-taking behaviors (See PAIN-E 6 of 13 of the NCCN Guidelines for Adult Cancer Pain)
• The panel endorses the ASCO Policy Brief on Opioid Therapy and Access to Treatment (2016), particularly as it relates to weighing the risks/
benefits of opioid treatment.

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Survivorship Pain
UNIVERSAL SCREENING ASSESSMENT CANCER PAIN TREATMENTb

SYNDROMES
• Quantify pain intensity

and characterize
quality Comprehensive pain
See Pain Intensity assessment (See [PAIN-C]
Rating (PAIN-A) from the NCCN Guidelines Neuropathic pain See (SPAIN-4)
from the NCCN for Adult Cancer Pain) in
Guidelines for Adult order to identify pain Chronic pain syndromes
If pain (amputation, neck dissection, See (SPAIN-5)
Cancer Pain • Etiologya
present mastectomy, thoracotomy)
• Severe uncontrolled • Pathophysiology
pain is a medical • Determine patient goals
emergency and for comfort, and function Myalgias, arthralgias See (SPAIN-6)
should be addressed • Specific cancer pain
promptly syndrome
Rule out oncologic Skeletal pain See (SPAIN-7)
emergency
Screen for
cancer pain Myofascial pain See (SPAIN-8)
or cancer
Rescreen at each
treatment- If no pain
subsequent visit
related pain Gastrointestinal/urinary/
at regular See (SPAIN-9)
pelvic pain
intervals
Post-radiation pain See (SPAIN-10)
See Procedure-Related Lymphedema See (SLYMPH-1)

Anticipated
Pain and Anxiety (PAIN-B)
painful events
from the NCCN Guidelines
and procedures
for Adult Cancer Pain
aReferralto primary care physician for non-cancer treatment-related workup and pain management (ie, rheumatoid arthritis) and consider the possibility of pain due to
cancer recurrence.
bSee General Principles of Pain Management (SPAIN-1).

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Survivorship Pain
CANCER PAIN TREATMENT

SYNDROME
• General measures:
Adjuvant analgesics
(See [PAIN-G] from the NCCN Guidelines for Adult Cancer Pain)
◊ SNRIs
◊ Anticonvulsants
◊ Tricyclic antidepressants (TCAs)
Opioids and dual-action opioid agonist/noradrenaline reuptake inhibitord
See (PAIN-3, PAIN-4, and PAIN-5) from the NCCN Guidelines for Adult Cancer Pain
CBT and psychosocial support
Neuropathic painc (See [PAIN-H] from the NCCN Guidelines for Adult Cancer Pain)
• Paresthesias ◊ Consider hypnosis
(tingling or prickling) Local therapies
• Shooting, "electrical" ◊ Pharmacologic therapies
• Numbness – Topical patches (ie, lidoderm, capsaicin)
– Compounded creams (eg, lidocaine, baclofen, ketamine, and amitriptyline
combined)
◊ Non-pharmacologic therapies
– Heat
– Ice
– Acupuncture
– Transcutaneous electrical nerve stimulation (TENS) unit
• For refractory pain, consider referral to pain management services, interventional
specialist, physical therapy, physical medicine and rehabilitation, and/or palliative care
cAlsosee NCCN Guidelines for Adult Cancer Pain and Hershman DL, Lacchetti C, Dworkin RH, et al. Prevention and management of chemotherapy-induced peripheral
neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 2014;32:1941-1967.
dSee Principles of Opioid Use in Long-Term Survivors (SPAIN-2).

SPAIN-4

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Survivorship Pain
CANCER PAIN TREATMENT TREATMENT

SYNDROME
• For post-amputation syndrome:

Physical therapy for desensitization
◊ Consider mirror therapy
• General measures:
Cognitive therapy
Adjuvant analgesics
Upper extremities:
See (PAIN-G) from the NCCN Guidelines
◊ Consider stellate ganglion block
Lower extremities:
Psychosocial support and behavioral
Chronic pain ◊ Consider lumbar sympathetic block
interventions
syndrome Neuromas:
See (PAIN-H) from the NCCN Guidelines
(amputation, Specific ◊ Consider phenol/alcohol block
neck chronic pain • For post-radical neck dissection syndrome:
Opioidsd
dissection, syndromese Physical therapy for stretching, range of
See (PAIN-3, PAIN-4, and PAIN-5) from the
mastectomy, motion
NCCN Guidelines for Adult Cancer Pain
thoracotomy) Myofascial release
• For refractory pain, consider referral to
Soft tissue massage
pain management services, interventional
Trigger point injections
specialist, orthopedic services,
Possible botulinum toxin injection
physical therapy, physical medicine and
• For post-mastectomy or post-thoracotomy
rehabilitation, and/or palliative care
syndrome:
Intercostal nerve block
TENS unit

eThere are other postoperative pain syndromes and many treatment measures can be used across syndromes. Also consider referral to appropriate specialist.

SPAIN-5

Table of Contents
Survivorship Pain

SYNDROME
• Nonpharmacologic
Physical activity (category 1 for aromatase inhibitor-induced arthralgia)
Heat (ie, paraffin wax, hot pack)
Cold pack
Aquatic therapy
Ultrasonic stimulationf
Massage
Acupuncture (category 1 for aromatase inhibitor-induced arthralgia)
Yoga
Myalgias, Arthralgias • Pharmacologicg
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Muscle relaxants
Anticonvulsant drugs (ie, gabapentin, pregabalin)
SNRIs (category 1 for aromatase inhibitor-induced arthralgia)
TCAs
Acetaminophen
COX-2 inhibitors
• Consider referral to pain management services, interventional specialist, physical therapy,
physical medicine and rehabilitation, orthopedic services, and/or palliative care
fUltrasonicstimulation is a type of heat treatment that can penetrate directly to the bone and should be used with caution. It is not recommended for patients with
multiple myeloma or bone metastases.
gConsider switching to an alternative aromatase inhibitor (AI) or tamoxifen for AI-induced arthralgia.

SPAIN-6

Table of Contents
Survivorship Pain

SYNDROME
• For vertebral compression:
General measures:
◊ Bisphosphonates or other antiresorptive medications if appropriate
◊ NSAIDs
◊ Muscle relaxants
◊ Consider vertebral augmentation (ie, vertebroplasty, kyphoplasty)
◊ Acetaminophen
◊ COX-2 inhibitors
Consider referral to pain management services, interventional specialist, physical
therapy, physical medicine and rehabilitation, orthopedic services, and/or palliative care
For acute vertebral compression:
◊ Opioidsd
◊ Bracing (ie, thoracolumbar sacral orthosis [TLSO], Jewett brace)
◊ Limited bedrest
Skeletal painh ◊ Weight-bearing exercises when pain improves
◊ Physical therapy
For chronic vertebral compression:
◊ Weight-bearing exercises
◊ Physical therapy – thoracic and lumbar stabilization exercises
• For avascular necrosis:
Physical therapy – based on weight-bearing and range-of-motion restrictions
Opioidsd
Muscle relaxants if myofascial component
Core decompression
• For osteonecrosis of the jaw:
Referral to oral surgeon
Anti-convulsants
SNRIs
Opioidsd

hFor skeletal metastases and/or bone pain, see (PAIN-D) from the NCCN Guidelines for Adult Cancer Pain. Consider orthopedic/surgical referral.

SPAIN-7

Table of Contents
Survivorship Pain

SYNDROME
• Nonpharmacologic
Physical activity
Range-of-motion exercises
Strengthening exercises
Soft tissue/myofascial release massage
Ultrasonic stimulationf
Acupuncture or acupressure
• Pharmacologic
Myofascial paini Topical ointments (ketamine) and patches (ie, lidocaine, capsaicin)
NSAIDs
Anticonvulsant drugs
SNRIs
Acetaminophen
COX-2 inhibitors
• Consider referral to pain management services, interventional specialist,
physical therapy, physical medicine and rehabilitation, and/or palliative care
for services such as trigger point injections
fUltrasonic stimulation is a type of heat treatment that can penetrate directly to the bone and should be used with caution. It is not recommended for patients with
multiple myeloma or bone metastases.
iFor muscle cramps or spasms, check electrolytes, calcium and magnesium levels, and hydration status.

SPAIN-8

Table of Contents
Survivorship Pain

SYNDROME
• For gastrointestinal pain (abdominal pain/cramping):

Adequate hydration
Consider referral to gastroenterologist
• For chronic pelvic pain:j

Consider referral to specialist in pelvic floor pain such as urologist, gynecologist, or
physical medicine and rehabilitation
Consider physical therapy for pelvic floor exercises
Adequate hydration
Gastrointestinal/urinary/pelvic pain
Bowel regimen
Dorsal column stimulation for chronic cystitis and chronic pelvic pain
• For dyspareunia: (See SSF-2)

Consider referral to gynecologist or sexual health specialist
• For refractory gastrointestinal/urinary/pelvic pain:

Consider referral to pain management services, interventional specialist, physical
therapy, physical medicine and rehabilitation, and/or palliative care
jMultidisciplinary treatment for chronic pelvic pain is preferred if available.

SPAIN-9

Table of Contents
Survivorship Pain

SYNDROME
• Treat according to specific cancer pain syndrome guidelines, if appropriate

Post-radiation pain
(See SPAIN-3 for list of cancer pain syndromes)
• Pain may be acute or appear months or years after
• Physical therapy
radiation
• Pain medication (appropriate to the etiology)
• Radiation may lead to scarring, adhesions, or fibrosis
• Surgical lysis of adhesions may be indicated in extreme circumstances
Differentiate fibrosis from recurrent tumor
• Consider referral to pain management services, interventional specialist,
• Radiation to a localized area of the body (ie, head and
physical therapy, physical medicine and rehabilitation, orthopedic services,
neck, breast) may cause a chronic pain syndrome in
and/or palliative care for post-radiation pain including after stereotactic
that area
body RT (SBRT)

SPAIN-10

Table of Contents
Survivorship Sexual Function (Female and Male)
DIAGNOSTIC EVALUATION Re-evaluate and

Screening discuss potential
questions do not impact of treatment
indicate an issue on sexual function at
future visits
• Ask about sexual

Refer to sexual health
function at regular
specialist, if survivor is
intervals
Screening questions interestedc
(See screening
indicate an issue, but and
questions on SURV-A)
survivor does not want to Re-evaluate and discuss
• Discuss treatment-
discuss at oncology visit potential impact of
associated infertility
• H&P treatment on sexual
if indicated, with
• Review oncologic history (ie, diagnosis/stage, function at future visits
appropriate referralsa
surgeries, systemic treatment, local RT, endocrine
therapy) See Treatment for
• Explore treatment-related impact on sexual Females (SSF-2) or for
function Males (SSF-3)
• Screening questions
• Assess for signs or symptoms of estrogen or Appropriate referrals for:
indicate an issue and
androgen deprivation or refer to appropriate • Psychotherapy
survivor wants to
specialist • Sexual/couples
discuss further
• Review medical history for conditions associated counseling
• Consider use of a
with sexual dysfunction (eg, depression [See • Gynecologic care
screening toolb
SANXDE-1 and NCCN Guidelines for Distress • Urology
Management], diabetes, hypertension) • Sexual health
• Assess total morning testosterone in males as specialist, if availablec
indicated
• Review medication list for drugs that impact
sexual function (eg, SSRIs, beta blockers)
aForinformation regarding fertility preservation for patients with cancer, see Loren AW, Mangu PB, Beck LN, et al. Fertility preservation for patients with cancer:
American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2013;31:2500-2510. http://www.ncbi.nlm.nih.gov/pubmed/23715580
bSeveral Screening tools are available for both men and women. For women, options include the Brief Sexual Symptom Checklist for Women (SSF-A), Arizona Sexual
Experience Scale (http://dx.doi.org/10.1080/009262300278623), and the Female Sexual Function Index (http://www.fsfiquestionnaire.com/). For men, the
Sexual Health Inventory for Men (SHIM) (SSF-B), Sexual-Quality of Life-Men (http://dx.doi.org/10.1111/j.1743-6109.2007.00749.x), and the PROMIS Brief Function
Profile-Male (http://www.assessmentcenter.net/) are examples.
cSexual health specialists may come from a range of backgrounds, including primary care, gynecology, urology, oncology, psychology, and/or rehabilitation medicine.
Whenever possible, survivor should be referred to an appropriate local resource for further sexual health evaluation.

SSF-1

Table of Contents
Survivorship Sexual Function (Female)
SYMPTOMS TREATMENT OPTIONSd FOLLOW-UP

Symptoms of menopause
(See SMP-1), vaginal dryness, or
other issues related to vaginal See SMP-5
health Concerns
(eg, discomfort, discharge, pain) regarding
sexual Re-evaluate at
function regular intervals
Discussion of available drugs
Low or lack of desire, improved or
(ie, androgens, bupropion,g buspirone,g
libido, or intimacy resolved
flibanserin, bremelanotide)h
• Topical vaginal therapies (See SMP-5)
(OTC or prescription)
• Vaginal dilators
Female with Symptoms of pain with • Ospemifenee
concerns/issues sexual activity • DHEAf
regarding sexual • Pelvic physical therapy Refer to
function • Topical anesthetics appropriate health
(OTC or prescription) Ongoing
concerns care provider for
• Discussion of options regarding further evaluation,
Problems with orgasm including vibrator or clitoral sexual workup, and/or
(eg, less intensity, stimulatory device with referral function treatment:
difficulty achieving, pain) to appropriate specialistc • Primary care
• Pelvic physical therapy • Gynecology
Global symptoms of distress, • Psychology (may
anxiety, depression, or other See SANXDE-1 include couples
psychological concerns counseling)
• Sexual health
Multiple issues identified specialistc
cSexual health specialists may come from a range of backgrounds, including primary care, gynecology, urology, oncology, psychology, and/or rehabilitation medicine.
Whenever possible, survivor should be referred to an appropriate local resource for further sexual health evaluation.
dDiscuss risk/benefits of prescription medications if not contraindicated for cancer type or refer to appropriate health care provider (eg, sexual health specialist) for
prescription and/or treatment as necessary.
eCurrently ospemifene is contraindicated in survivors with a history of estrogen-dependent cancers.
fDHEA should be used with caution in survivors with a history of estrogen-dependent cancers.
gBupropion and buspirone may be considered as off-label treatments for hypoactive sexual desire disorder, despite limited safety and efficacy data.
hThere is a lack of data showing a benefit of sildenafil in women or of flibanserin and androgens in cancer survivors. In addition, there is a lack of safety data for the use
of androgen-based therapy in survivors of hormonally mediated cancers.

SSF-2

Table of Contents
Survivorship Sexual Function (Male)
SYMPTOMS TREATMENT OPTIONS FOLLOW-UP

• Oral phosphodiesterase type 5 (PDE5) inhibitors as needed,
if not contraindicated.i
• If total morning testosterone <300 ng/dL, then testosterone
therapy may be indicatedj
• Daily low-dose oral PDE5 inhibitors, if not contraindicated
Erectile dysfunction
• Lifestyle modification (HL-1) (eg, increased physical Concerns
activity, smoking cessation, reduction of alcohol regarding
consumption, weight loss if obese) sexual
• Pelvic physical therapy Re-evaluate at
function
regular intervals
improved
If total morning testosterone <300 ng/dL (repeat second
Low or lack of desire, or
morning total testosterone and free T, LH, and prolactin),
libido, or intimacy resolved
testosterone therapy may be indicated.
• If total morning testosterone <300 ng/dL (repeat second
morning total testosterone and free T, LH, and prolactin),
Male with testosterone therapy may be indicatedj
concerns/ Problems with ejaculation • Psychological evaluation
issues (premature, absent, SSRIs (paroxetine, sertraline, citalopram, fluoxetine) Ongoing
regarding delayed, or climacturia) dosed daily concerns
sexual function Clomipramine dosed on demand regarding
• Pelvic physical therapy sexual
Refer to appropriate
• For climacturia: Empty bladder prior to sex, pelvic physical function
health care
therapy, or trial of imipramine provider for further
• If total morning testosterone <300 ng/dL (repeat evaluation, workup,
second morning total testosterone and free T, LH, and/or treatment:
Problems with orgasm and prolactin), then testosterone therapy may be • Primary care
• Urology
(eg, less intensity, indicatedj
difficulty achieving, pain) • Psychology (may
• Vibratory therapy
include couples
• PDE5 inhibitors, if not contraindicated
counseling)
Global symptoms of distress, • Pelvic physical therapy
• Sexual health
anxiety, depression, or other See SANXDE-1 specialistc
psychological concerns
Multiple issues identified
cSexual health specialists may come from a range of backgrounds, including primary care, gynecology, urology, oncology, psychology, and/or rehabilitation medicine. Whenever
possible, survivor should be referred to an appropriate local resource for further sexual health evaluation.
iDosing should be titrated to optimal effect.
jTestosterone therapy should only be used if not contraindicated by primary oncologic diagnosis (eg, prostate cancer on active surveillance, prostate cancer under therapy with
androgen deprivation).

SSF-3

Table of Contents
Survivorship Sexual Function (Female)
BRIEF SEXUAL SYMPTOM CHECKLIST FOR WOMEN1
Please answer the following questions about your overall sexual function:
1. Are you satisfied with your sexual function?
__ Yes __No
If no, please continue.
2. How long have you been dissatisfied with your sexual function?
3a. The problem(s) with your sexual function is:

(mark one or more)
__1 Problem with little or no interest in sex
__2 Problem with decreased genital sensation (feeling)
__3 Problem with decreased vaginal lubrication (dryness)
__4 Problem reaching orgasm
__5 Problem with pain during sex
__6 Other:
3b. Which problem is most bothersome? (circle)

1 2 3 4 5 6
4. Would you like to talk about it with your doctor?

__Yes __No
1Reprinted with permission from Hatzichristou D, Rosen RC, Derogatis LR, et al. Recommendations for the clinical evaluation of men and women with sexual
dysfunction. J Sex Med 2010;7:337-348.

SSF-A

Table of Contents
Survivorship Sexual Function (Male)
SEXUAL HEALTH INVENTORY FOR MEN (SHIM)1

Sexual health is an important part of an individual's overall physical and emotional well-being. Erectile dysfunction, also known as impotence, is one type of
very common medical condition affecting sexual health. Fortunately, there are many different treatment options for erectile dysfunction. This questionnaire
is designed to help you and your doctor identify if you may be experiencing erectile dysfunction. If you are, you may choose to discuss treatment options
with your doctor.
Each question has several possible responses. Circle the number of the response that best describes your own situation.
Please be sure that you select one and only one response for each question.
OVER THE PAST 6 MONTHS:
1. How do you rate your Very Low Low Moderate High Very High
confidence you could get
and keep an erection? 1 2 3 4 5
2. When you had erections No Sexual Activity Almost Never A Few Times Sometimes Most Times Almost Always
with sexual stimulation, how or Never (Much Less Than (About Half (Much More Than or Always
often were your erections Half The Time) the Time) Half The Time)
hard enough for penetration
(entering your partner)? 0 1 2 3 4 5
3. During sexual intercourse, Did Not Attempt Almost Never A Few Times Sometimes Most Times Almost Always
how often were you able to Intercourse or Never (Much Less Than (About Half (Much More Than or Always
maintain your erection after Half The Time) the Time) Half The Time)
you had penetrated (entered)
your partner? 0 1 2 3 4 5
4. During sexual intercourse, Did Not Attempt Extremely Difficult Very Difficult Difficult Slightly Difficult Not Difficult
how difficult was it to maintain Intercourse
your erection to completion of
intercourse? 0 1 2 3 4 5
5. When you attempted sexual A Few Times Sometimes Most Times Almost Always
Did Not Attempt Almost Never
intercourse, how often was it (Much Less Than (About Half (Much More Than or Always
Intercourse or Never
satisfactory for you? Half The Time) the Time) Half The Time)
0 1 2 3 4 5
PROVIDER KEY: Add the numbers corresponding to questions 1-5. TOTAL: __________
The SHIM further classifies ED severity with the following breakpoints: 1-7: Severe ED 8-11: Moderate ED 12-16: Mild to Moderate ED 17-21 Mild ED
1Reproduced and modified with permission from Cappelleri JC, Rosen RC. The Sexual Health Inventory for Men (SHIM): a 5-year review of research and clinical experience. Int J Impot
Res 2005;17:307-319.

SSF-B

Table of Contents
Survivorship Sleep Disorders
Re-evaluate
SCREENING No concerns for sleep at subsequent
a disorder/disturbance visits/post
Screening/assessment questions H&P therapy
to be asked at regular intervals, • Assessment of treatable or modifiable
especially when there is a change contributing factors:
in clinical status or treatment: Comorbidities Insomnia symptoms
◊ Alcohol and/or substance abuse (difficulty falling
• Are you having problems falling ◊ Obesity asleep staying
asleep, staying asleep, or waking ◊ Cardiac dysfunction asleep, or waking up See
up too early? ◊ Respiratory disorders too early):d SSD-2
• Are you experiencing excessive ◊ Endocrine dysfunction (eg, hypothyroidism) • Duration >4 weeks
sleepiness (sleepiness or falling ◊ Anemia • Occurring at least
asleep in inappropriate situations – Iron and ferritin levels 3 times per week
or sleeping more during a 24-hour ◊ Emotional distress: screen for anxiety and
period than in the past?) Concerns for depression (See SANXDE-1 and NCCN
• Have you been told that you snore sleep Guidelines for Distress Management)
frequently or stop breathing disorder/ ◊ Neurologic disorders including
during sleep? disturbanceb chemotherapy-induced peripheral neuropathy
◊ Psychiatric disorders
Medicationsc
Sleep disturbance and/or
Vasomotor symptoms
excessive sleepinessd
(see SMP-4 [females) and SMP-6 [males])
• Hypersomnias See
Review sleep/wake timing and/or sleep log/diary
• Obstructive sleep apneae SSD-3
Review caffeine intake
• Restless legs syndrome
Review history of cancer treatments
(RLS)e,f
Pain (See SPAIN-1)
Shift work
Current coping strategies
(eg, relaxation techniques, meditation)
aThe following additional tools may be used for individual intensive screening to
assess sleep quality: PSQI https://www.sleep.pitt.edu/instruments/#psqi and
PROMIS SLEEP http://www.healthmeasures.net/index.php?option=com_instrume dIn the differential diagnosis of insomnia or excessive sleepiness symptoms,
nts&view=measure&id=183&Itemid=992. consider parasomnia or circadian rhythm sleep disorders and referral to a sleep
bPatients may have more than one sleep disorder. specialist.
cConsider persistent use of sleep aids, pain medications, antiemetics, stimulants, eNote that obstructive sleep apnea, RLS, circadian rhythm sleep disorders, and
antidepressants, anti-psychotics, sedative/hypnotics, opioids, over-the-counter parasomnia may also present with symptoms of insomnia.
sleep aids, or antihistamines. fRLS is also known as Willis-Ekbom disease.

SSD-1

Table of Contents
EVALUATION TREATMENT
Evaluate for
Insomnia and address
disorder secondary
that is causes • Sleep hygiene educationh,i
problematic, • Medical • CBTj (preferred)k
causing: • Neurologic • Pharmacologic intervention,l if safe, for:
• Decreased • Psychiatric Difficulty in falling asleep
daytime • Pain Difficulty maintaining sleep
functioning • Shift work • Refer to sleep specialist or PCP for
• Poor quality • Medications chronic or refractory symptoms (≥3
of life that may cause months)
• Distress to insomnia
patient • Environmental
Obtain details about • Sleep hygiene
characteristics and
course of insomnia
• Sleep hygiene educationh,i

Circadian rhythm disorderg
• Refer to sleep specialist or PCP
gCircadian rhythm disorder: A chronic or recurrent pattern of sleep-wake rhythm disruption due primarily to an alteration of the circadian timing system or to a
misalignment with the sleep-wake schedule required by an individual’s physical environment or social/work schedules.
hSee General Sleep Hygiene Measures (SSD-A).
iSleep hygiene alone has not been shown to be effective, but should be part of the initial treatment of all survivors with sleep disorders and as a prevention strategy for
insomnia disorder. Sleep hygiene alone is not the recommended treatment for insomnia, but should be used in conjunction with other treatments such as CBT-I and/or
pharmacotherapy.
jSee Cognitive Behavioral Treatments (SSD-B).
kCBT is preferred over pharmacologic interventions as first-line therapy.
lSee Principles for Choosing an FDA-Approved Hypnotic (SSD-C).

SSD-2

Table of Contents
SYMPTOM ASSESSMENTm TESTING DIAGNOSISm TREATMENT

Associated with Sleep log Insufficient • Increase time for sleep
insufficient sleep time or diary sleep syndrome • Sleep hygiene educationr
Refer to sleep specialist or
Associated with observed PCP for further evaluation
• Refer to sleep specialist
apneas, snoring n or
Obstructive or PCPs
Sleep studyq
sleep apnea • Weight loss (See HL-1)
• Exercise (See SPA-1)
Management options:
• Iron replacement as clinically
Sleep indicated
disturbance • Initial preferred therapy
History and physical exam
and/or Gabapentin
(See SSD-D)
Excessive RLSf,o Enacarbil
and evaluate for iron
sleepinessd Associated with Dopamine agonists
deficiency
uncomfortable sensationo • Opioids
or
• Clonazepam
Refer to sleep specialist or
• Sleep hygiene educationr
PCP for further evaluation • Refer to a sleep specialist or PCP
Associated with:
• Prolonged wakefulness or awakenings
• Prolonged nocturnal sleep (ie, >9 hours for adults)
• Cataplexy,p frequent short naps, vivid dreams,
disrupted sleep, or sleep paralysis
Refer to a sleep specialist
• Circadian rhythmn disorderg
Excessive daytime sleepiness not associated with other symptoms
dIn the differential diagnosis of insomnia or excessive sleepiness symptoms, consider parasomnia
or circadian rhythm sleep disorders and referral to a sleep specialist.
fRLS is also known as Willis-Ekbom disease. oSee Essential Diagnostic Criteria for Restless Legs Syndrome (SSD-D).
gCircadian rhythm disorder: A chronic or recurrent pattern of sleep-wake rhythm disruption due pCataplexy: Sudden loss of muscle tone, typically triggered by strong emotions, such as laughter or
primarily to an alteration of the circadian timing system or to a misalignment with the sleep- anger. Cataplexy is the most specific diagnostic feature of narcolepsy.
wake schedule required by an individual’s physical environment or social/work schedules. qSleep studies can be done as laboratory polysonography or as home sleep study. However,
mFor other less frequent syndromes, refer to a sleep specialist. survivors with known cardiac disease or neurologic disease, who have used opiates for cancer-
nThe following tools may be used to assess sleep apneas: STOP Questionnaire (Chung F, related pain, may not be good candidates for some home sleep tests.
Yegneswaran B, Liao P, et al. STOP questionnaire: a tool to screen patients for obstructive rSee General Sleep Hygiene Measures (SSD-A).
sleep apnea. Anesthesiology 2008;108:812-821) and Berlin Questionnaire sThe most common medical treatment for obstructive sleep apnea is continuous positive airway
(http://sleepapnea.org/wp-content/uploads/2017/02/berlin-questionnaire.pdf). pressure (CPAP).

SSD-3

Table of Contents
GENERAL SLEEP HYGIENE MEASURES1,2,3

• Maintain a regular bedtime and waketime every day.
• Engage in regular physical activity in the morning and/or afternoon (See SPA-1). Avoid moderate to strenuous physical activity within 3
hours of bed time.
• Increase exposure to bright light during the day.
• Reduce exposure to bright light (ie, computer, phone screens, light sources close to the eye) within a few hours before bedtime and during
the night.
• Avoid heavy meals and limit fluid intake within 3 hours of bedtime.
• Avoid alcohol and nicotine too close to bedtime.
• Limit caffeine consumption and avoid caffeine consumption at least 4 hours before bedtime.
• Enhance sleep environment
(dark, quiet room; comfortable temperature).
• Set aside a worry time before bedtime.
• Avoid looking at the clock when awake during the night.
• If necessary, limit to 1 short nap per day in the afternoon (no longer than 30 min).
• Turn off electronics and light-emitting sources at bedtime.
1National Heart, Lung, and Blood Institute Working Group on Insomnia. Insomnia: Assessment and Management in Primary Care. 1998. NIH Publication. 98-4088.
2Kupfer DJ and Reynolds CF. Management of insomnia. N Engl J Med 1997;336:341-346.
3Lippmann S, Mazour I, Shahab H. Insomnia: therapeutic approach. South Med J. 2001;94:866-873.

SSD-A

Table of Contents
COGNITIVE BEHAVIORAL TREATMENTS1
Strategy Goal
Stimulus control Associate the bed/bedroom as a place for sleep or sexual

activity only
Sleep restriction Improve sleep continuity by:

• Limiting time spent in bed2
• Maintaining a regular sleep schedule by keeping a standard
bedtime and wake time every day
Cognitive therapy3 or Challenge survivor's maladapative beliefs and misconceptions

internet-based cognitive about sleep disturbances
behavioral therapy
Relaxation training • Reduce physiologic and cognitive arousal at bedtime

• Techniques include progressive muscular relaxation, deep
breathing, meditation, yoga, and biofeedback
1Data from Bootzin RR and Perlis ML. Nonpharmacologic treatments of insomnia. J Clin Psychiatry 1992;53(suppl):37-41.
2Match total amount of time spent in bed to the actual amount of time spent sleeping (no less than 5 hours).
3Johnson JA, Rash JA, Campbell TS, et al. A systematic review and meta-analysis of randomized controlled trials of cognitive behavior therapy for insomnia (CBT-I) in
cancer survivors. Sleep Med Rev 2016;27:20-28.

SSD-B

Table of Contents
PRINCIPLES FOR CHOOSING AN FDA-APPROVED HYPNOTIC:1,2,3,4
• Does the patient have difficulty initiating or maintaining sleep?

• Does the patient have both sleep onset and sleep maintenance difficulty?
AGENT HELPS WITH INCREASES TOTAL INDICATED FOR

SLEEP INITIATION SLEEP TIME SLEEP INITIATION
AND
MAINTENANCE
Zolpidem + + –
Zolpidem CR + + +
Zaleplon + – –
Eszopiclone + + +
Ramelteon + ± –
Temazepam + + +
Doxepin (3–6 mg) – + +
Suvorexant + + +
1Data from the Physicians’ Desk Reference (ed 66). Montvale, NJ: PDR Network, LLC; 2012.
2Inform patients that taking hypnotic medications may cause complex sleep-related behaviors (eg, sleep driving, sleep eating).
3Other commonly used medications for insomnia include sedating medications such as antidepressants (ex, trazodone), antihistamines, atypical anti-pyschotics, other
benzodiazepine receptor agonists, and nutritional/herbal supplements (ex, melatonin). They do not have an FDA-approved indication for the treatment of insomnia, and
do not have enough data to be recommended for routine use.
4Most of these agents, with the exception of ramelteon, doxepin, and suvorexant, are benzodiazepine receptor agonists and can be associated with dependence, abuse,
and withdrawal. Assessment for the continued need of hypnotics is recommended every 1–3 months.

SSD-C

Table of Contents
ESSENTIAL DIAGNOSTIC CRITERIA FOR RESTLESS LEGS SYNDROME1
• An urge to move the legs usually accompanied by uncomfortable and unpleasant sensations in the legs, and sometimes the arms or other
body parts.
• The urge to move or unpleasant sensations begin or worsen during periods of rest or inactivity such as lying or sitting.
• The urge to move or unpleasant sensations are partially or totally relieved by movement, such as walking or stretching.
• The symptoms are more pronounced in the evening or night or may only occur in the evening or night.
IRON DEFICIENCY AND RESTLESS LEG SYNDROME
• Iron deficiency is a secondary cause of RLS and can also exacerbate symptoms.
• Treatment with iron replacement in survivors with documented iron deficiency can improve symptoms.
Recommend taking iron replacement with vitamin C (eg, orange juice) to enhance the absorption of oral iron.
Goal ferritin level is 50–75 μg/L or until alleviation of symptoms.2
1Reproduced with permission from Allen RP, Picchietti D, Hening WA, et al. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A
report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4:101-119.
2Winkelman JW, Armstrong MJ, Allen RP, et al. Practice guideline summary: Treatment of restless legs syndrome in adults: Report of the Guideline Development,
Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology 2016 Dec 13;87:2585-2593.

SSD-D

Table of Contents
NCCN Categories of Evidence and Consensus

Category 1 Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2A Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2B Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.
Category 3 Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.
All recommendations are category 2A unless otherwise indicated.

CAT-1
NCCN Guidelines Version 2.2020

Survivorship
Discussion This discussion corresponds to the NCCN Guidelines for Survivorship. Last updated on 07/14/2020.
Table of Contents
Overview ......................................................................................... MS-2 Lymphedema ............................................................................ MS-43

Literature Search Criteria and Guidelines Update Methodology ........ MS-2 Hormone-Related Symptoms ..................................................... MS-46
General Principles of These Guidelines ........................................... MS-3 Pain .......................................................................................... MS-52
Cancer Survivors ............................................................................. MS-4 Sexual Dysfunction ................................................................... MS-58
The Effects of Cancer and Its Treatment .......................................... MS-4 Sleep Disorders ........................................................................ MS-64
Physical Effects ........................................................................... MS-4 Summary ...................................................................................... MS-68
Subsequent Primary Cancers ....................................................... MS-4 References ................................................................................... MS-69
Psychosocial Effects .................................................................... MS-5
Fear of Recurrence ................................................................... MS-5
Employment Issues and Return to Work ................................... MS-6
Financial Burden....................................................................... MS-6
Standards for Survivorship Care ...................................................... MS-7
Models of Survivorship Care and the Role of Primary Care Providers
.................................................................................................... MS-8
Survivorship Care Planning .......................................................... MS-8
Surveillance for Cancer Recurrence ........................................... MS-10
Assessment for Effects of Cancer and Its Treatment ...................... MS-10
Reassessment .............................................................................. MS-11
Survivorship Research .................................................................. MS-12
Recommendations for Preventive Health ....................................... MS-12
Healthy Lifestyles ....................................................................... MS-12
Physical Activity ...................................................................... MS-13
Nutrition and Weight Management .......................................... MS-16
Supplement Use in Survivors .................................................. MS-19
Health Behavioral Change ......................................................... MS-20
Immunizations and Prevention of Infections ................................ MS-21
Recommendations for Specific Effects of Cancer and Its
Treatment…………………………………………………………………MS-24
Cardiovascular Disease Risk Assessment .................................. MS-24
Anthracycline-Induced Cardiac Toxicity ...................................... MS-25
Anxiety, Depression, Trauma, and Distress ................................ MS-31
Cognitive Dysfunction ................................................................ MS-35
Fatigue ...................................................................................... MS-39
MS-1
Version 2.2020 © 2020 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.

Survivorship
Overview The NCCN Survivorship Panel is comprised of a multidisciplinary panel of

The number of cancer survivors in the United States increased from experts that includes at least one oncologist, bone marrow transplant
approximately 3 million in 1971 to more than 16.9 million in 2019.1-3 This clinician, gynecologist, urologist, infectious disease specialist, cardiologist,
number is predicted to surpass 22 million by 2030.3 This striking increase PCP, psychologist, nutrition scientist, nurse, epidemiologist, social worker,
is generally attributed to rising cancer incidence rates (mainly resulting and patient advocate. The panel has defined general principles of cancer
from an aging population), earlier detection, and better treatment. survivorship to help guide the recommendations that form the basis for
these guidelines.13
Approximately 64% of survivors were 65 years of age or older in 2019.3
Only 5% are younger than 40 years, and survivors of childhood cancer Literature Search Criteria and Guidelines Update
constitute between 0.5% and 3.0% of the survivor population.4,5 In fact, an Methodology
estimated 1 of every 5 persons older than 65 years is a cancer survivor. Prior to the update of this version of the NCCN Guidelines for
The most common cancer sites in the survivor population are breast, Survivorship, an electronic search of the PubMed database was
prostate, colon/rectum, and melanoma, together accounting for performed to obtain key literature in the field of cancer survivorship, using
approximately 58% of survivors.4 Approximately 64% of survivors were the following search terms: (("neoplasms"[MeSH Terms] OR
diagnosed 5 or more years ago, whereas 15% of survivors were "neoplasms"[All Fields] OR "cancer"[All Fields]) AND ("survivors"[MeSH
diagnosed 20 or more years ago, and approximately 5% have survived 30 Terms] OR "survivors"[All Fields] OR "survivor"[All Fields])) OR
years or longer.4 (("neoplasms"[MeSH Terms] OR "neoplasms"[All Fields] OR "cancer"[All
Fields]) AND ("survivorship"[All Fields])). The PubMed database was
Unfortunately, many of these cancer survivors experience physical and/or chosen because it remains the most widely used resource for medical
psychosocial late and/or long-term effects of cancer and its treatment, literature and indexes peer-reviewed biomedical literature.14
which can be severe, debilitating, and sometimes permanent. Survivors
may be discharged from the care of their oncologist and feel isolated and The search results were narrowed by selecting studies in humans
scared. Furthermore, their primary care physicians (PCPs), who may now published in English. Results were confined to the following article types:
be responsible for their care, often do not know how best to care for the Clinical Trial, Phase II; Clinical Trial, Phase III; Practice Guideline;
specific concerns and needs of cancer survivors.6 ASCO’s statement, Randomized Controlled Trial; Meta-Analysis; Systematic Reviews; and
“Achieving High-Quality Cancer Survivorship Care,” cites a need for Validation Studies.
standardized, evidence-based practice guidelines for the management of
The data from key PubMed articles and articles from additional sources
treatment effects and health promotion of survivors.7 ASCO, NCCN, ACS,
deemed as relevant to these guidelines and discussed by the panel have
and other groups that are working in parallel hope to provide this
been included in this version of the Discussion section (eg, e-publications
guidance.8-12
ahead of print, meeting abstracts). Recommendations for which high-level
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Survivorship
evidence is lacking are based on the panel’s review of lower-level relevant to this population (eg, those around fatigue, anxiety, depression).
evidence and expert opinion. The panel emphasizes that these guidelines may be used to guide the
management of all cancer survivors – not just those who have completed
The complete details of the Development and Update of the NCCN treatment, but also the population with chronic cancer.
Guidelines are available on the NCCN website (www.NCCN.org).
These guidelines should be used as a supplement to the follow-up
General Principles of These Guidelines recommendations within the disease-specific guidelines (see NCCN
These NCCN Guidelines for Survivorship provide screening, evaluation, Guidelines for Treatment of Cancer by Site, available at www.NCCN.org)
and treatment recommendations for common consequences of cancer and and should provide a framework for the coordination of care between the
cancer treatment to aid health care professionals who work with survivors survivor’s health care providers to ensure that needs are appropriately
of adult-onset cancer, including those in specialty cancer survivor clinics addressed.
and primary care practices. These guidelines are focused on options to
maintain and enhance wellness in cancer survivors who are receiving or These guidelines are not intended to provide guidance for the care of
have completed active therapy, including those receiving treatment for survivors of childhood cancer (detailed guidelines for the care of childhood
years, those who may be in remission, and those who are cured. These cancer survivors are available from the Children’s Oncology Group at
guidelines are designed to provide a framework for the management of http://www.survivorshipguidelines.org/). For survivorship issues related to
long-term and/or late effects of cancer and its treatment. The guidelines younger populations, please also see the NCCN Guidelines for Adolescent
focus on the vast and persistent impact both the diagnosis and treatment and Young Adult (AYA) Oncology (available at www.NCCN.org). For
of cancer can have on the adult survivor's health, physical and mental survivors treated with immunotherapy, ongoing surveillance for immune-
states, health behaviors, professional and personal identity, sexuality, and mediated toxicities is warranted (see the NCCN Guidelines for
financial standing. Management of Immunotherapy-Related Toxicities, available at
www.NCCN.org).
The panel acknowledges that there is a growing population of cancer
survivors with chronic cancer. This group includes those with incurable For this version of the NCCN Guidelines for Survivorship, the panel
disease who are receiving systemic therapy continuously and those who focused on the preventive health issues including healthy lifestyle
may be on treatment intermittently. Although these guidelines do not behaviors, immunizations and prevention of infection, and cardiovascular
address the specific needs of survivors with chronic cancer (eg, disease (CVD) risk assessment and modification. The panel also focused
psychosocial issues related to living for years with a terminal diagnosis on several common issues of survivors: 1) anthracycline-induced cardiac
and uncertainty about the future; how to handle comorbid conditions and toxicity; 2) anxiety, depression, trauma, and distress; 3) cognitive decline;
disease prevention, screening, and treatment in the setting of limited life 4) fatigue; 5) lymphedema; 6) hormone-related symptoms; 7) pain; 8)
expectancy; managing discussions around new drugs and early-stage female and male sexual dysfunction; and 9) sleep disorders. Additional
clinical trials),15 many of the recommendations in these guidelines are topics will be addressed in subsequent updates.
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Survivorship
Cancer Survivors of various effects of cancer and its treatment are hard to quantify, because
The NIH adapted the definition of a cancer survivor from the National few studies have addressed these issues in a longitudinal fashion,
Coalition for Cancer Survivor and states: “An individual is considered a comparing patients with and without a history of cancer to differentiate
cancer survivor from the time of diagnosis, through the balance of his or between the effects of cancer and the effects of aging.18 In general, the
her life. There are many types of survivors, including those living with prevalence of late effects in cancer survivors is believed to have increased
cancer and those free of cancer. This term is meant to capture a over time, likely because anticancer interventions have become more
population of those with a history of cancer rather than to provide a label complex and intense with combinations of surgery, radiation,
that may or may not resonate with individuals.”16 chemotherapy, hormone therapy, and targeted biologics.28
Physical Effects
The Effects of Cancer and Its Treatment
Physical effects of cancer and its treatment in cancer survivors include
For some survivors, the consequences of cancer are minimal; these
pain, musculoskeletal issues, fatigue, lack of stamina, urinary and bowel
patients can return to a normal life after the completion of treatment. In
problems, lymphedema, premature menopause, cognitive deficits,
fact, most cancer survivors report being in good general health and
diabetes, and sexual dysfunction.18,29-32 The effects of cancer treatment on
experience good to excellent quality of life.17,18 Also, a survey of 659
the heart and bone are also well known.33-36 The type of physical effects
survivors of breast, colorectal, and prostate cancers found that a majority
depends mainly on the treatment received. For example, radiation to the
do not suffer from psychologic morbidity or have a large number of unmet
supportive care needs.19,20 Other studies have similarly found that most pelvis can be associated with bowel, urinary, and sexual dysfunction and
increased risk for subsequent primary malignancies.37,38 The ACS Study of
survivors enjoy a high quality of life without a large number of cancer-
related symptoms.21,22 Cancer Survivors II found that 38% of survivors reported at least one
unmet need in the physical domain (eg, pain, sexual dysfunction).24
However, many survivors do experience physical and/or psychosocial
effects of cancer and its treatment.23-25 Some sequelae become evident Subsequent Primary Cancers
during anticancer treatment (long-term effects), whereas others may not Importantly, the overall incidence of subsequent primary cancers in
manifest for months or years after active therapy (late effects). The survivors is higher than in the general population because of genetic
problems can range from mild to severe, debilitating, or even life- susceptibilities (eg, hereditary cancer syndromes), shared causative
threatening. Some problems are temporary or improve with time, whereas factors (eg, smoking, obesity, environmental exposures, human
other problems are progressive or permanent. This topic has been well papillomavirus [HPV] infection), and/or the mutagenic effects of cancer
reviewed.18,26 treatment.39-50 In fact, subsequent cancers accounted for 18% of all
cancers diagnosed in the United States between 2009 and 2013.51
A literature review suggests that at least 50% of survivors experience Treatment-related subsequent primary cancers vary with the type and
some late effects of cancer treatment.26 The most common problems in intensity of anticancer treatment and are associated in particular with
cancer survivors are depression, pain, and fatigue.27 The exact prevalence radiation and specific chemotherapeutic agents.52-58 These subsequent
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malignancies are especially well studied in long-term survivors of Genetic counseling and testing is recommended for appropriate survivors
childhood cancers.59-62 Studies by individual cancer type show that the based on results of the risk assessment. Referral to genetic risk
incidence of subsequent unrelated cancers ranges from 2% in survivors of assessment and/or testing should be considered for appropriate
malignant lymphoma to 30% in survivors of small cell lung cancer candidates when available to identify those with an increased risk for
(SCLC).26 Another study of more than 2 million cancer survivors in the subsequent malignancies. Genetic testing may also provide opportunities
SEER database identified the highest risk for subsequent primary cancers to identify and reduce risks in relatives of cancer survivors. Several NCCN
in survivors of bladder cancer (34% at 20 years).63 Overall, this study Guidelines (available at www.NCCN.org) include criteria for genetic risk
found that 8.1% of survivors of cancers diagnosed after age 18 years assessment and testing, and management recommendations for patients
develop a subsequent malignancy within a mean follow-up of 7.1 years, with known germline mutations linked to an increased risk for cancer, as
with 55% of these survivors dying as a result of the subsequent cancer. listed above in these guidelines.
Screening for subsequent primary cancers should be a shared Psychosocial Effects

responsibility between primary and oncology care physicians (see the Cancer can have positive effects on a significant portion of individuals,
NCCN Guidelines for Detection, Prevention, & Risk Reduction, available at including strengthened relationships, a sense of gratitude or
www.NCCN.org). In addition, lifestyle modifications that reduce the risk of empowerment, and an increased appreciation for life.66-72 Many survivors,
subsequent primary cancers (eg, smoking cessation, physical activity, however, experience psychologic distress after active treatment, and
weight loss) should be encouraged.64 Finally, referral to genetic risk some experience a combination of positive and negative psychologic
assessment and/or testing should be considered for appropriate effects. Distress can result from the fear of recurrence or death or
candidates, such as those with a cancer diagnosis at a young age or with secondary to physical, social, or practical problems.66,69,73 In fact, as many
multiple primary cancers, to identify those with a potential increased risk as 19% of survivors meet the criteria for post-traumatic stress disorder
for subsequent malignancies.65 Family cancer history should be (PTSD).66,69,74-76 Practical and social problems of survivors include issues
periodically updated to reassess hereditary risk, because it should not be surrounding employment, finances, and health and life insurance.66,77-80
assumed that all cancer survivors were assessed at diagnosis. Genetic
testing guidelines and knowledge about hereditary cancer risk evolve over Fear of Recurrence
time, and new family diagnoses may occur making periodic assessment As many as 70% of post-treatment cancer survivors report high levels of
important. Genetic risk assessment is appropriate for all survivors of fear of cancer recurrence, which can cause significant and enduring
breast cancer, epithelial ovarian cancer, high-grade prostate cancer, distress.69,81-84 In addition, caregivers report distress from fear of cancer
pancreatic cancer, and colorectal or endometrial cancer diagnosed at age recurrence in their loved one.85 These fears and their associated distress
50 years or younger. Many other survivors of rare cancers, cancers may cause survivors and their caregivers to either avoid appropriate
diagnosed at young ages, multiple primary cancers, or those with one or surveillance or to demand more intense surveillance than evidence
more relatives with the same or related cancers are also candidates for supports.84 In addition, survivors with high levels of fear of recurrence are
risk assessment per guidelines from NCCN and other expert groups. more likely to be depressed and have a lower quality of life.86
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Survivorship
Employment Issues and Return to Work Financial Burden

Cancer and its treatment often have an adverse effect on work status, The LIVESTRONG 2012 Survey found that approximately 33% of working-
performance, and satisfaction.87 Survivors often take long breaks from or age survivors went into debt and 3% had filed for bankruptcy.105 The ACS
even leave their jobs during treatment, and returning to work after cancer Study of Cancer Survivors II found that 20% of survivors reported unmet
treatment can be critical to restoring normalcy to the lives of survivors. financial needs.24 A study in Washington state found that patients with
However, survivors may be left with disabilities or late/long-term effects cancer have a 2.6-fold increased risk of bankruptcy.106 In another study,
that decrease their employment prospects or ability to perform at their 38% of patients with stage III colon cancer reported financial hardship
previous levels. Several studies have shown that unemployment rates for resulting from cancer treatment, defined as accruing debt, selling or
survivors are higher than for the general population.87-90 Furthermore, refinancing a home, borrowing money from friends or family, or
those survivors who do return to work often encounter difficulties, such as experiencing a ≥20% decline in annual income.107 Another study found
physical or cognitive limitations, fatigue, depression, anxiety, and that, in addition to the average >$16,000 excess economic burden that
perceived or real discrimination.87,91,92 patients feel in the early phases of cancer treatment, survivors (>1 year
from diagnosis) have an average annual excess economic burden that
Several studies have addressed factors that predict a delayed return to exceeds $4,000.108,109 Much of this excess burden was because of excess
work.93-99 For example, a French population-based study revealed that medical expenditures. A more recent study found that the excess annual
clinical factors, such as severity of the cancer, receipt of chemotherapy, or health care expenditures of cancer survivors averaged about $4400, and
the experience of adverse effects, were associated with a delay in return that the total mean annual direct health care expenditure for cancer
to work.97 In addition, a systematic review of cohort studies found that survivors increased by about $1000 in the period from 2009 to 2010 to the
survivors who were older, had a lower education level, or had a lower period from 2015 to 2016.109 Other recent studies also found that cancer
income were less likely to return to work.98 Another systematic review survivors have greater out-of-pocket expenses and are more likely to
identified factors related to the person (eg, symptoms, coping, motivation), experience material hardship than those without a history of cancer.110,111
environmental supports (eg, family, workplace), and occupation (eg, type Younger cancer survivors seem to be particularly vulnerable to the
of work, job flexibility) that impacted successful return to work after cancer financial effects of cancer.111-113
treatment.100
Clearly, with lost wages and increased expenses, the financial burden on
Some interventions to enhance return-to-work in cancer survivors have many cancer survivors is great. Recent data suggest that patients
been studied (eg, psycho-education, physical training, vocational belonging to racial and ethnic minorities are more likely to suffer financial
counseling), although additional research in this area is greatly needed.101- hardship after cancer treatment.114,115 Furthermore, the financial burden
104
Multidisciplinary interventions that combine vocational counseling with associated with cancer treatment and survivorship can lower health-
other elements (eg, patient education, patient counseling, behavioral related quality of life, increase psychologic distress, and impact adherence
training, physical exercises) may increase rates of return-to-work to prescribed medications.116-119
compared to usual care.
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Standards for Survivorship Care elements of survivorship care. After 2 days of consensus building, the
In 2005, the Institute of Medicine (IOM) (now known as the National group agreed on the following elements that all medical settings must
Academy of Medicine [NAM]) and the National Research Council compiled provide for cancer survivors, either directly or through referral
a report entitled, “From Cancer Patient to Cancer Survivor: Lost in (http://images.livestrong.org/downloads/flatfiles/what-we-do/our-
Transition.”28 The NCCN Survivorship Panel adapted the essential approach/reports/ee/EssentialElementsBrief.pdf):
components of survivorship care from the report: 1. Survivorship care plan, psychosocial care plan, and treatment
1. Prevention of new and recurrent cancers and other late effects summary
2. Surveillance for cancer spread, recurrence, or subsequent cancers 2. Screening for new cancers and surveillance for recurrence
3. Assessment of late psychosocial, physical, and immunologic 3. Care coordination strategy that addresses care coordination with
effects PCPs and primary oncologists
4. Intervention for consequences of cancer and treatment (eg, 4. Health promotion education
medical problems, symptoms, psychologic distress, financial and 5. Symptom management and palliative care
social concerns)
The 2020 Commission on Cancer (CoC) of the American College of
5. Coordination of care between primary care providers and
Surgeons’ accreditation standards for hospital cancer programs
specialists to ensure that all of the survivor’s health needs are met
(https://www.facs.org/quality-programs/cancer/coc/standards/2020) has a
6. Planning for ongoing survivorship care (see below)
patient-centered focus that recommends and encourages, but does not
In addition, the IOM report discusses the importance of policies that require, the development and dissemination of a survivorship care plan for
ensure access to and health insurance coverage for all aspects of all patients completing primary therapy. The current standard requires the
survivorship care, including psychosocial services. Cancer survivors with development and implementation of a survivorship program directed at
untreated distress have poorer compliance with surveillance screenings meeting the ongoing needs of survivors treated with curative intent. More
and are less likely to exercise and quit smoking.120 A 2008 IOM report, information can be found on its website.
“Cancer Care for the Whole Patient: Meeting Psychosocial Health
Implementation of these standards for survivorship care has been
Needs,”121 concluded that psychosocial screening and care should be a
challenging, and reasons for the difficulties have been described.122-124 To
part of the new standard for quality cancer care and should be integrated
move toward the goal of personalized pathways to ensure that all cancer
into routine care across the trajectory of cancer, which includes the period
survivors receive all essential components of care, an ACS-ASCO summit
after active treatment. See the NCCN Guidelines for Distress Management
identified the following necessary strategies: 1) developing candidate care
(available at www.NCCN.org) and Anxiety and Depression below for
delivery models; 2) conducting implementation studies to model the effects
recommendations on screening for and treating distress.
of personalized follow-up care pathways on survivor outcomes, workforce
In September 2011, the LIVESTRONG Foundation convened a meeting of and health care resources, and utilization and costs; 3) developing
experts and stakeholders in the survivorship field to define essential
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guidelines to inform the personalized care pathway delivery; and 4) breast cancer survivors (10% increase in year 4 after diagnosis; P <
identifying and filling research gaps.123 .05),141 these results show that PCPs are providing a substantial amount of
survivorship care. In fact, according to IOM analyses of the 2001 and 2002
Models of Survivorship Care and the Role of Primary Care National Ambulatory Medical Care Survey and the National Hospital
Providers
Ambulatory Medical Care Survey, approximately one-third of the more
Various models have been proposed to facilitate the implementation of all than 36 million cancer-related visits to physicians’ offices were made to
the essential components of survivorship care for the growing population primary care.28 Furthermore, a nationally representative survey by NCI and
of post-treatment cancer survivors. These include survivorship clinics the ACS found that >50% of PCPs provide survivors with cancer-related
within academic or community cancer centers, community survivorship follow-up care, often with co-management by oncologists.142
clinics run by primary care clinicians, and survivorship care in the primary
care setting.125-130 In each case, survivorship care is delivered by either In a survey of survivors regarding their preferences for follow-up care,
physicians or by advanced practice clinicians such as nurse most participants said that the PCP should only provide care if the
practitioners.131 Each model has advantages and disadvantages, and no responsibility was shared with the oncologist.143 One of the reasons
one model is clearly the best for all situations. commonly cited for this preference was that survivors believe their PCPs
lack the needed expertise to deal with their specific issues. In addition,
With the population of cancer survivors growing at a rapid pace, the survivors cited a desire for continuity of care. Additional surveys of
demand for follow-up care is expected to increase. An increasing survivors of breast cancer in the United States and of survivors of breast,
proportion of this care will likely be performed by primary care teams. In colorectal, and prostate cancer in the United Kingdom found similar
fact, a systematic review identified specific needs of cancer survivors in preferences for oncologist-driven follow-up care over PCP follow-up
the primary care setting, including psychosocial needs, cancer/survivor care.144,145 Importantly, however, two randomized trials comparing
information needs, and medical needs.132 Because studies have shown survivorship care administered by PCPs (provided guidelines outlining
that primary care providers often do not know how best to care for the appropriate follow-up care) versus oncologists found no difference in
specific concerns and needs of cancer survivors,6,133-138 education for disease-related outcomes, including survival.146,147
primary health care providers regarding appropriate survivorship care will
be increasingly important.139 Survivorship Care Planning
Because primary care offices are in fact already caring for cancer
A study in the Netherlands found that patients with cancer 2 to 5 years
survivors, it is critical for information to be shared between oncology and
after diagnosis increased their number of consultations with primary care
primary care teams. Good communication at the oncology/primary care
compared with age- and sex-matched controls without cancer by 15% for
interface may allow survivors to feel they have the continuity of care they
colorectal cancer (P < .05), 24% for breast cancer (P < .001), and 33% for
desire.
prostate cancer (P < .001).140 These survivors also had more chronic
conditions than controls. Although an American study using the SEER-
Medicare database showed a smaller increase in primary care use by
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Some data suggest that treatment summaries and survivorship care plans than in the usual care group (P = .003). Patient adherence to
lead to improvements in outcomes for survivors, such as having fewer recommended survivorship care, the secondary outcome, was also
emotional concerns and more often reporting that their needs have been greater for the intervention group, but did not reach statistical significance
met.148,149 However, a randomized controlled trial of 408 survivors of breast (P = .07). Whereas this trial provides support for the benefits of
cancer that assessed the effects of survivorship care plans found no survivorship care plans, it is impossible to separate the effects of the care
differences on patient-reported outcomes, including cancer-specific plan and the intensive counseling session, and the applicability of the
distress, between patients who received a discharge visit and a care plan findings to other populations is unknown. Another randomized controlled
and those who received only a discharge visit.150,151 Criticisms of this trial, trial examined the efficacy of mailing a personalized survivorship care
including the relevance of its outcome measures, have been published.152- plan, which was designed with qualitative input of hematopoietic cell
154
Another trial randomized 221 survivors of stage I–III colorectal cancer transplant survivors and briefly reviewed in a telehealth call by a trained
to usual care or usual care plus a supportive care package that included a non-professional.149 The study randomized 458 hematopoietic cell
survivorship care plan, educational materials, a needs assessment, an transplant survivors 1 to 5 years after transplant to receive the survivorship
end-of-treatment session, and three follow-up telephone calls.155 No care plan or delayed survivorship care plan. After 6 months, the
effects on distress, supportive care needs, or quality of life were seen, survivorship-care-plan recipients reported reduced cancer-specific distress
although survivors in the care plan group were more satisfied with their and improved general mental health, although they did not report higher
care. In addition, a trial in which 12 hospitals were randomized to usual levels of confidence in survivorship information when compared with the
care or to patient-tailored, automated survivorship care plans found that delayed care plan recipients as hypothesized. In this study, about two-
the receipt of a care plan was associated with an increase in symptoms, thirds of survivors reported that they found the survivorship care plan
concern about illness, and emotional impact.156 No differences in useful in helping them understand their treatments and side effects, and
satisfaction with information or care were evident. helpful in managing their health. Another randomized trial found that a
survivorship care plan, discussed in consultation with a physician who had
More recent population-targeted randomized controlled trials are lending received skills training, increased patient knowledge about their disease
some support for the benefits of survivorship care planning. One and increased adherence to certain health promotion recommendations.158
randomized controlled trial tested the role of survivorship care plans in 212 A third trial did not see an increase in survivors’ knowledge after provision
low-income, predominantly Latina survivors of stage 0–III breast cancer.157 of a survivorship care plan.159 At this time, definitive data supporting the
Survivors in the intervention group received the care plan with a treatment benefits of survivorship care plans are still insufficient.160
summary and a 1-hour counseling session with a trained, bilingual,
bicultural nurse who encouraged patient empowerment; the care plan and A survey that included a nationally representative sample of 1130
treatment summary were also delivered to the health care providers of oncologists found that fewer than 5% of them provide a written
survivors in the intervention group. Patient-reported physician survivorship care plan to survivors.161 The survey also included 1020
implementation of recommended survivorship care (eg, for depression, hot PCPs, who were nine times more likely (95% CI, 5.74–14.82) to have
flashes), the primary trial outcome, was greater in the intervention group survivorship discussions with survivors if they received a written care plan.
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More recent surveys have reported that 35% to 40% of survivors receive a health risks when possible (See NCCN Guidelines for Treatment of
written follow-up care plan and/or a written treatment summary.162,163 Cancer by Site)
 Delineation regarding roles of oncologists, PCPs, and subspecialty
ASCO released a clinical expert statement on cancer survivorship care care physicians in long-term care and timing of transfer of care if
planning in 2014.164 The group of experts identified barriers to the appropriate
successful implementation of survivorship care planning (including the  Healthy behavior recommendations
time it takes to complete one, the lack of reimbursement for doing so, and
 Periodic assessment of ongoing needs and identification of
the uncertainty as to whose responsibility it is to prepare the plan) and
appropriate resources
revised the ASCO survivorship care plan template to help address some
Data from ongoing trials will help inform future recommendations.
of these barriers. In addition, a pilot study assessed the use of electronic
health records (EHRs) to reduce the time and effort involved with creating Surveillance for Cancer Recurrence
care plans.165 Although many plan elements required manual entry by the
Screening for cancer recurrence is an important aspect of survivorship
oncologist, the median time to complete the plans was only 3 minutes
care. In general, this surveillance is performed by the oncology team.
(range 2–12 minutes). Another group reported on a similar initiative to
When surveillance is overseen by the primary care team, the oncologist
facilitate generation of care plans using EHRs.166 Care plan creation took a
should provide evidence-based recommendations based on currently
mean 12 minutes (range 10–15 minutes). However, a study in which EHR-
available guidelines. Specific recommendations for surveillance testing
based treatment summaries were abstracted and cross-checked revealed
vary between cancer site and stage and individualized patient risk and are
that 30% contained ≥1 omissions, and 10% contained ≥1 errors, indicating
not addressed in these guidelines. Please see individual NCCN Guidelines
that autopopulation systems will require manual double-checking to
for Treatment of Cancer by Site (available online at www.NCCN.org) for
ensure accuracy.167 Thus, providing a survivorship care plan is time-
disease-specific surveillance recommendations. Additional lab work,
consuming and resource-intensive and could have unforeseen harms.154,168
imaging studies, or other studies to evaluate for recurrence should be
Because definitive evidence that survivorship care plans improve based on clinical presentation and judgment. The use of radiologic
outcomes is lacking, the NCCN Survivorship Panel currently recommends imaging studies (ie, CT) should be based on evidence that early detection
planning for ongoing survivorship care, but does not mandate the use of of recurrence will improve cancer-related outcomes, because evidence
survivorship care plans. The planning should include: suggests that excess radiation exposure associated with CT imaging may
be associated with an increased risk of developing a radiation-associated
 Information on treatment received including all surgeries, radiation
cancer.169,170
therapy, and systemic therapies
 Information regarding follow-up care, surveillance, and screening Assessment for Effects of Cancer and Its Treatment
recommendations
All survivors should be assessed at least annually for symptoms related to
 Information on post-treatment needs, including information
cancer and prior cancer treatment, with appropriate follow-up care as
regarding acute, late and long-term treatment-related effects, and
clinically indicated. This assessment can be done by the oncologist or
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PCP. Shared, coordinated care between the oncology, primary care, and 9. Disease-specific recommendations for surveillance/follow-up (see
subspecialty care providers is encouraged. Depending on the cancer type NCCN Guidelines for Treatment of Cancer by Site, at
and stage of disease, transition of care to primary care may be done when www.NCCN.org)
deemed clinically appropriate, with referral back to oncologic care as
needed. The panel does not assume that all survivorship issues will be This information can also inform about the patient’s risk for specific late or
addressed at every visit. long-term effects, including risks for subsequent primary cancers and
comorbidities. For example, patients who received pelvic irradiation or
Some tools that screen for long-term and late physical and psychosocial surgery are at risk for sexual dysfunction; patients with a history of brain
effects of cancer and its treatment in survivors have been validated.171-176 metastasis or cranial irradiation have an elevated risk for cognitive
In addition, the NCCN Survivorship Panel created a sample screening dysfunction. In general, those who underwent more intensive therapy are
instrument that is guideline-specific and can be self-administered or at higher risk for multiple late and/or long-term effects. Survivors
administered by an interviewer. This assessment tool was developed undergoing certain treatments, such as mantle field radiation or certain
specifically for use in combination with the NCCN Guidelines for systemic therapies, may be at increased risk for subsequent malignancies.
Survivorship to help providers deliver necessary and comprehensive Those survivors who continue to smoke are at increased risk for smoking-
survivorship care. Although this instrument has not yet been piloted or related comorbidities and subsequent primary cancers.
validated, the answers can be used to guide providers to topics within the
guidelines that require more in-depth assessment via validated tools Reassessment
and/or clinical evaluation. Survivors should be followed and reassessed at regular intervals,
depending on the nature and severity of late and long-term effects being
In addition to screening by history and physical examination, care
treated. At each time point, assessment of disease status and ongoing
providers should assess the following at regular intervals:
effects of cancer and its treatment should be addressed. In addition,
1. Current disease status
survivors should be periodically rescreened for the development of new
2. Functional/performance status
late and long-term effects of cancer and its treatment. The outcomes of
3. Medication use (including over-the-counter medications and
any interventions for ongoing effects of cancer and its treatment should be
supplements)
evaluated regularly based on best practices and available resources.
4. Comorbidities
Outcome assessment may include survivor satisfaction with the
5. Prior cancer treatment history and modalities used
effectiveness of the intervention in reducing symptom burden, adequate
6. Family history
pain control, receipt of recommended immunizations and preventive care,
7. Psychosocial factors
and improved adherence to guideline recommendations for health
8. Weight and health behaviors that can modify cancer and
behaviors.
comorbidity risk (including cigarette/tobacco, alcohol use)
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Survivorship Research significant comorbidities, smoke, are obese, and/or do not engage in
The IOM survivorship report cites a paucity of longitudinal cohort studies physical activity.183 Analysis of data from other studies, including the
linking specific cancer types or treatments with specific late effects, National Health Interview Survey, showed similar results.184-187 Separate
making it difficult to predict risk for individual patients.28 Research is surveys by the ACS and the CDC found that 9.3% and 17% of survivors
needed to increase understanding of the prevalence of, mechanisms of, smoke, respectively.186,188 In addition, many survivors forego
and risks factors for late and long-term effects of cancer and its treatment. recommended cancer screenings (ie, colorectal and cervical screening)
In addition, research is needed to better define interventions that relieve and follow-up surveillance189-191 or demand more intense surveillance than
symptoms, restore function, and improve the quality of life of survivors.177 evidence supports.84
Finally, research can help better define optimal follow-up and surveillance
Healthy Lifestyles
schedules for cancer survivors after treatment.178,179
Healthy lifestyle habits, such as engaging in routine physical activity,
An ASCO survey report highlighted several key gaps in current maintaining a healthy diet and weight, and avoiding cigarette/tobacco use,
survivorship research.180 For instance, more research pertaining to have been associated with improved health outcomes and quality of life.
survivors >65 years of age, to survivors of cancers other than breast, and For some cancers, a healthy lifestyle has been associated with a reduced
to long-term survivors (>5 years) is needed. In addition, research focused risk of recurrence and death.192-199 In fact, the maintenance of a healthy
on patterns and quality of survivorship care is lacking. A study of NIH lifestyle is associated with a decrease in premature death in cancer
survivorship grants in fiscal year 2016 showed a need for research survivors.200 Therefore, survivors should be encouraged to achieve and
including more diverse cancer types, older and longer-term survivors, and maintain a healthy lifestyle, including attention to weight management,
more ethnoculturally diverse populations of survivors.181 physical activity, metabolic health, and dietary habits. Setting incremental
goals for diet, physical activity, and weight management should be
In June 2012, the ACS, CDC, LIVESTRONG Foundation, and NCI held a advised. Survivors should be counseled to limit alcohol intake and avoid or
joint meeting and created an action plan to facilitate the translation of stop using cigarette/tobacco products, with emphasis on tobacco
survivorship research into survivorship care.182 The plan is driven by cessation if the survivor is a current smoker or user of smokeless tobacco
collaboration between researchers, survivors, clinicians, and public health (see the NCCN Guidelines for Smoking Cessation, available at
professionals; the use of technology, such as EHRs; analysis of www.NCCN.org).201 Clinicians should also advise survivors to practice sun
information from the viewpoints of multiple stakeholders; and the safety habits as appropriate, such as using a broad-spectrum sunscreen,
integration and synthesis of knowledge using systematic reviews and avoiding peak sun hours, and using physical barriers. Survivors should
meta-analyses. also be encouraged to get an adequate amount of sleep. Finally, survivors
should be encouraged to see a PCP regularly and adhere to age-
Recommendations for Preventive Health appropriate and treatment-associated health screenings, preventive
Analysis of data from the Behavioral Risk Factor Surveillance System measures (eg, immunizations), and cancer screening recommendations.
(BRFSS) indicates that a large proportion of cancer survivors have
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The panel made specific recommendations regarding physical activity, In addition, observational studies have consistently found that physical
weight management, nutrition, and supplement use, which are discussed activity is linked to decreased cancer incidence and recurrence and
herein. Although achieving all of these healthy lifestyle goals may be increased survival for certain tumor types.209,222-239 For example, one meta-
difficult for many survivors, even small reductions in weight among analysis of 6 studies including more than 12,000 survivors of breast
overweight or obese survivors or small increases in physical activity cancer found that post-diagnosis physical activity reduced all-cause
among sedentary individuals are thought to yield meaningful mortality by 41% (P < .00001) and disease recurrence by 24% (P =
improvements in cancer-specific outcomes and overall health.202 Clinicians .00001).226 Data from other meta-analyses primarily consisting of
should assess individual and community-level barriers to meeting the observational studies of survivors of colorectal, ovarian, non-small cell
healthy lifestyle recommendations and support patients in developing lung, brain, prostate, and breast cancers show that physical activity is
strategies to overcome challenges. associated with decreased all-cause mortality and/or cancer-specific
mortality.224,227,236,240 In fact, analyses of data from 986 survivors of breast
Physical Activity
cancer from the National Runners' and Walkers' Health Studies found that
During cancer treatment, many survivors become deconditioned and can mortality decreased with increased rates of energy expenditure.237
develop impaired cardiovascular fitness because of the direct and Evidence in other disease sites is less robust, but also suggests survival
secondary effects of therapy.203 Randomized trials have shown that benefits associated with exercise in survivors after treatment.240
exercise training is safe, tolerable, and effective for most survivors.
Structured aerobic and resistance training programs after treatment can Data also support the idea that inactivity/sedentary behavior is a risk factor
improve cardiovascular fitness and strength and can have positive effects for cancer incidence and mortality and impacts mood and quality of life in
on balance, body composition, fatigue, emotional well-being, and quality of survivors, independent of the level of an individual’s recreational or
life.204-216 The effectiveness of exercise is especially well studied in women occupational physical activity.192,241-247 For example, in a cohort of more
with early-stage breast cancer. Survivors of breast cancer who exercise than 2000 survivors of nonmetastatic colorectal cancer, those who spent
have improved cardiovascular fitness and therefore an increased capacity more leisure time sitting had a higher mortality than those who spent more
to perform daily life functions, resulting in a better quality of life.214,215,217-219 time in recreational activity.192
Furthermore, a study of adult survivors of childhood Hodgkin lymphoma
found that vigorous exercise was associated with a reduction in the risk of Evaluation and Assessment for Physical Activity
major cardiovascular events after a median follow-up of 11.9 years.220 In Survivors should be asked about readiness for participation in and their
fact, the finding was dose-dependent, and survivors who reported ≥9 current level of physical activity at regular intervals. The Godin Leisure-
metabolic equivalent (MET) h/wk experienced a 51% reduction in risk Time Exercise Questionnaire is one tool that can be used to assess a
compared with those reporting <9 MET h/wk (P = .002). A similar study in survivor’s exercise behavior, with a modified version also able to assess
patients with breast cancer found a similar reduction in the risk of daily time in moderate-to-vigorous activity.248,249
cardiovascular events with ≥9 MET h/wk.221
For survivors who are not meeting the guideline recommendations (see
later discussion), barriers to physical activity should be discussed and
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addressed, if possible. Common barriers include not having enough time specialist can also be considered. Specialized training in working with
to exercise, not having access to an acceptable exercise environment, survivors is available for both physical therapists and exercise
uncertainty about safety of exercise post-treatment, lack of knowledge professionals through the American College of Sports Medicine (ACSM;
regarding appropriate activities, and physical limitations.250 Alleviation of http://www.acsm.org/get-certified) and the American Physical Therapy
pain, fatigue, distress, or nutritional deficits can facilitate the initiation of an Association (APTA) Oncology section (http://oncologypt.org/). Survivors
exercise program. should be encouraged to use an ACSM- or APTA-certified trainer when
available.
Risk Assessment for Exercise-Induced Adverse Events
Exercise is considered safe for most survivors.214,215,251 However, a Lymphedema is not a contraindication for physical activity, and no special
significant portion of survivors may have comorbid conditions or risk precautions are required for cardiovascular/aerobic exercise or strength
factors that make them unable to safely exercise without trained training of unaffected limbs (see Survivor Lymphedema Education,
supervision.252 Therefore, a risk assessment is required for all survivors below).255-260 Progressive resistance training under supervision is
before prescribing a specific exercise program.214,253 The type of cancer, recommended as part of treatment for survivors with lymphedema (see
treatment modalities received, and the number and severity of Treatment of Lymphedema, above).
comorbidities determine risk levels.251 Thus, disease and treatment history,
Survivors at high risk for exercise-associated adverse events include
late and long-term effects, and comorbidities should be assessed. A
those with a history of lung surgery or major abdominal surgery, an
standardized pre-participation screening questionnaire, such as the
ostomy, cardiopulmonary comorbidities (eg, chronic obstructive pulmonary
Physical Activity Readiness Questionnaire for Everyone (PAR-Q+),254 can
disease [COPD], congestive heart failure [CHF], coronary artery disease
also be considered to identify patients for whom unsupervised physical
[CAD], cardiomyopathy), ataxia, severe nutritional deficiencies, severe
activity is likely safe versus those for whom it may pose undue risk.
fatigue, or worsening/changing physical condition (eg, lymphedema
Survivors with peripheral neuropathy, poor bone health, arthritis, or exacerbation). These survivors should receive medical evaluation and
musculoskeletal issues are considered to be at moderate risk for exercise- clearance prior to initiation of an exercise program and referral to trained
induced adverse events. Stability, balance, and gait should be assessed in personnel for a supervised exercise program.251 In general, exercise
survivors with peripheral neuropathy and possibly in survivors with poor should be individualized to the participant based on current exercise level
bone health before they engage in exercise, and exercise choice should and medical factors and should be increased in terms of intensity,
be made based on the results (ie, stationary bike or water aerobics for duration, and frequency as tolerated.
survivors with poor balance). In addition, balance training can be
Physical Activity Recommendations for Survivors
recommended for patients at risk for falls. Moderate-risk survivors can
Both the ACS and the ACSM have made physical activity
often follow the general recommendations for physical activity; however,
recommendations for cancer survivors.212,261 In addition, the panel also
medical clearance and/or referrals to trained personnel such as a physical
considered the physical activity guidelines for Americans published by the
or occupational therapist, certified exercise professional, or rehabilitation
Department of Health and Human Services (HHS) and those on diet and
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physical activity for the prevention of cancer by the ACS.262,263 The panel include incremental increases in time spent in physical activity or in
supports the recommendations by these groups and has adapted them as intensity of activity over time. The panel suggested a possible initial
follows: physical activity prescription (starting inactive survivors with 1 to 3 light-
1. Physical activity and exercise recommendations should be tailored to /moderate-intensity sessions of 20 minutes or more per week), with
individual survivors’ abilities and preferences. progression based on tolerance.266 For survivors tolerating the minimum
2. Survivors who are able should be encouraged to engage in daily guideline recommendations, clinicians should consider encouraging
physical activity, including exercise, routine activities, and incremental increases in time spent in physical activity or in intensity of
recreational activities. activity. Walking and using a stationary bike are safe for virtually all
3. All survivors should be encouraged to limit sedentary behavior (eg, survivors.
sitting for long periods) and return to daily activities as soon as
possible. Resistance Training
4. Physical activity for cancer survivors: The health benefits of resistance training include improvement in muscle
 Overall volume of weekly activity should be at least 150 to 300 strength and endurance, improvements in functional status, and
minutes of moderate-intensity activity or 75 minutes of maintenance/improvement in bone density. Core and strength training is
vigorous-intensity activity, or an equivalent combination spread important to maintain balance and minimize fall risk. Studies in survivors
out over the course of the week; have shown improvements in lean body mass, muscular function, and
 Individuals should engage in 2 to 3 sessions per week of upper body strength, and a slowing of physical function deterioration.268-273
strength training (see Resistance Training, below) that include A recent systematic review of 15 studies of resistance training
major muscle groups; and interventions during and/or after cancer treatment concluded that
 Major muscle groups should be stretched at least 2 days per meaningful improvements in physiologic and quality-of-life outcomes can
week on days that other exercises are performed. be achieved.270 A similar review of 11 randomized controlled trials came to
similar conclusions.273 One recent study that included 2863 cancer
The panel acknowledges that most survivors do not meet these exercise survivors found resistance exercise to be associated with a 33% lower risk
recommendations, and a significant portion reports that they perform no of all-cause mortality (95% CI, 0.45–0.99), independent of aerobic
leisure-time activity.183,264 However, the evidence suggests that even light- exercise.274
intensity physical activity can improve physical functioning in survivors.265
All major muscle groups (chest, shoulders, arms, back, core, and legs)
For survivors who are inactive, clinicians should not advise the immediate
should be incorporated into a resistance training program. For survivors
initiation of a high-intensity, high-frequency program.266,267 Instead, the
who do not currently engage in resistance training, referral to trained
panel suggests that clinicians provide sufficient information to encourage
personnel or an exercise specialist is recommended if available. Clinicians
survivors to avoid a sedentary lifestyle.253 Survivors and providers should
should recommend 2 to 3 sets of each exercise at a weight that allows the
work together to address barriers to physical activity and develop
performance of 10 to 15 repetitions; however, individualizing
incremental short- and long-term physical activity goals. These goals may
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recommendations for resistance and strength training is important. majority of studies on weight and weight gain in survivors have been
Survivors can consider increasing the weight when 3 sets of 10 to 15 performed in survivors of breast cancer, but some studies have also been
repetitions become easy. done in survivors of other cancers. Weight gain or being overweight or
obese can exacerbate a survivor’s risk for functional decline, comorbidity,
Interventions to Increase Physical Activity and cancer recurrence or death, and can reduce quality of life.309,312-320 For
Dozens of studies have looked at the efficacy of a variety of behavioral example, a systematic review and meta-analysis of studies in survivors of
and exercise interventions for increasing exercise behavior in cancer breast cancer found a correlation between higher body mass index (BMI)
survivors.211,214,275-277 However, data comparing different interventions are and higher risk of total and breast cancer-specific mortality.314 Additionally,
limited, and there is currently no “best” physical activity program for cancer a meta-analysis demonstrated that this risk for increased breast cancer
survivors.278-281 Several studies have examined the physical activity and mortality is predominantly confined to the pre- and perimenopausal,
counseling preferences of survivors, with the goal of informing possible hormone receptor-positive population.321 A retrospective study of survivors
strategies to best encourage increased activity in this population.282-284 of stage II and III colon cancer enrolled in NSABP trials from 1989 to 1994
showed that survivors with a BMI of 35 kg/m2 or greater had an increased
The panel suggests several strategies to help increase physical activity.
risk of disease recurrence and death.193,197 In addition, some evidence
These strategies include a simple recommendation from a physician,
suggests that weight loss or gain increases mortality risk in survivors,
physical therapist, and/or certified exercise physiologist.285-287 In addition,
suggesting that weight maintenance is optimal.322
participation in supervised exercise programs or classes or enlisting the
support of an exercise group or buddy may be helpful for survivors.288-291 In ASCO published a position statement on obesity and cancer.323 The ASCO
addition, setting short- and long-term goals and considering the use of a panel established an initiative to reduce the impact of obesity on cancer
pedometer or wearable activity tracker to monitor these goals (eg, through education, tools, and resources for clinicians by promoting
achieving 10,000 steps per day) can be helpful.292-301 Print materials, research (eg, in health behavioral change) and advocating for policies that
telephone counseling, motivational interviewing, and theory-based can help patients with cancer manage their weight.
behavioral approaches (discussed in Health Behavioral Change, below)
are other strategies that may be effective for increasing physical activity in Nutrition and Weight Management Assessment
the survivor population.289,296,302-307 Combination approaches (eg, oncologist The BMI of survivors should be evaluated at regular intervals. A BMI of
recommendation plus exercise DVDs, pedometers, exercise diaries, 18.5 to 24.9 kg/m2 is considered ideal. It is important to inform patients of
exercise education sessions) may also increase exercise participation in their weight status, particularly if they are underweight (BMI <18.5),
survivors.308 overweight (BMI = 25–29.9), or obese (BMI ≥30), and discuss the
importance of interventions to attain a normal body weight and avoid
Nutrition and Weight Management
weight gain in adulthood. The panel notes, however, that BMI should be
Weight gain after cancer diagnosis and treatment is common, and the considered in context of body composition. For more muscular survivors,
prevalence of obesity in the survivor population is greater than in the waist circumference may be a better measure of overall disease risk. A
general population and has increased at a faster rate.309-311 The vast
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waist circumference of >35 inches for women and >40 inches for men weight throughout life in survivors with a BMI in the normal range. In
increases risk for diabetes, hypertension, and CVD.324 particular, the importance of avoiding high-calorie, low-nutrient foods (eg,
regular soft drinks, sugary desserts, fried foods) and focusing on lower-
Current dietary and physical activity habits and potential barriers to calorie, high-nutrient foods (eg, vegetables [especially those lower in
physical activity or a healthful diet of those in high-risk groups should be starch], broth-based soups, fresh fruit for desserts, and beverages such as
ascertained either by the oncologist or other appropriate allied health water, unsweetened tea, and black coffee) is especially important.
personnel (eg, nurses, dietitians). In addition, effects of cancer treatment
and other medical issues, including psychosocial distress and fear of Recommendations for Overweight/Obese Survivors
recurrence, should be assessed and addressed as necessary. Survivors with a BMI in the overweight or obese range should be engaged
in discussions about nutrition, weight management, and physical activity,
Weight Management for Survivors
as outlined in these guidelines. In addition, clinicians should specifically
Providers should discuss strategies to prevent weight gain for normal and
discuss portion control; substituting high-calorie foods with low-calorie,
overweight/obese survivors. Clinicians should reinforce the importance of
healthful, nutrient-dense foods; and tracking diet, calories, and physical
maintaining a normal body weight throughout life and encourage all cancer
activity. Clinicians should also refer overweight/obese survivors to a PCP
survivors to achieve and maintain a normal BMI and strive for metabolic
or appropriate hospital-based or community resources. Furthermore,
health. In conjunction with primary care, survivors should be assessed for
contributing psychosocial factors should be assessed and addressed.
metabolic health, body composition, and BMI. Regardless of BMI, all
Referrals can also be made to a registered dietitian, especially those who
survivors should be advised about the panel’s nutrition, weight
are Certified Specialists in Oncology Nutrition (CSO) or members of the
management, and physical activity recommendations (see pages SNWM-
Oncology Nutrition Dietetic Practice Group of the Academy of Nutrition
1, SNWM-2, and SPA-1 in the algorithm, above). Contributing treatment
and Dietetics. Diet, exercise, and behavioral modification are the
effects and risk factors should be managed as clinically indicated. In
cornerstones of weight management; however, in cases of morbid obesity,
addition, a workup for disease recurrence should be considered in the
pharmacologic agents or bariatric surgery can be considered with
setting of involuntary weight loss or gain of >5% within 3 months or if
appropriate referral to primary care and other providers. Of note, the
cachexia is present.
safety and efficacy of weight loss drugs or bariatric surgery in cancer
For additional resources, see the ASCO Tool Kit on Obesity and Cancer survivors are currently unknown.
(https://www.asco.org/practice-policy/cancer-care-initiatives/prevention-
Randomized trials have shown that intensive behavioral weight loss
survivorship/obesity-cancer) and the LIVESTRONG MyPlate Calorie
interventions can lead to weight loss in overweight/obese cancer
Tracker (http://www.livestrong.com/myplate/).
survivors.325-330 For example, the ENERGY trial used a group-based
behavioral intervention with telephone counseling and newsletters and
Recommendations for Normal Weight Survivors
achieved a 6.0% weight loss compared with a 1.5% weight loss in the
In addition to discussing nutrition, weight management, and physical
control group at 12 months.330 In general, however, these trials see some
activity, clinicians should reinforce the importance of maintaining a normal
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Survivorship
weight regained in survivors at the end of the intervention; maintenance of with a dietary fat intake of ≥32% of energy were randomized 3:2 to a usual
weight loss remains a challenge in this population.325 diet group or a dietary intervention group.338 After an average follow-up of
8.1 years, 655 (0.42%) women in the intervention group and 1072 women
Recommendations for Underweight Survivors (0.45%) in the comparison group developed invasive breast cancer (HR,
Survivors with a BMI in the underweight range should be engaged in 0.91; 95% CI, 0.83–1.01). Furthermore, after a median cumulative follow-
discussions about nutrition (see below), and contributing psychosocial up of 19.6 years in the WHI Dietary Modification trial, a significant
factors should be assessed and addressed. In addition, advising reduction in deaths after breast cancer that was seen after earlier follow-
underweight survivors to increase their frequency of eating and to avoid up persisted (HR, 0.85; 95% CI, 0.74–0.96; P = .01) and a significant
fluid intake with meals may help with weight gain. Furthermore, smoking reduction in deaths as a result of breast cancer emerged (HR, 0.79; 95%
status, dental health, swallowing and taste/smell disorders, and CI, 0.64–0.97; P = .02).339
gastrointestinal motility should be assessed and addressed as
appropriate. Foods that are both high in calories and nutrient-dense (eg, Data also suggest that healthy dietary patterns (as characterized by plant-
avocados, nuts) should be encouraged. Consideration can also be given based diets that have ample amounts of fruits, vegetables, and whole
to referral to a registered dietitian for individualized counseling. grains, with limited quantities of red and processed meats and refined
grains and sugars) are associated with a decrease in cancer recurrence
Nutrition in Survivors and improved outcomes in survivors.212,340-342 In survivors of stage III colon
Systematic reviews and meta-analyses of observational studies have cancer, a diet consisting of more fruits, vegetables, whole grains, poultry,
shown that healthy dietary patterns are associated with a decreased risk and fish, and less red meat, refined grains, and concentrated sweets was
of primary cancer development and improved subsequent outcomes.331-334 found to be associated with an improved outcome in terms of cancer
A population study in England with >65,000 participants found that recurrence and death, as well as overall survival.343 Higher dietary
consumption of ≥7 servings daily of fruit and vegetables reduced cancer glycemic load (associated with high intakes of refined starches and
incidence by 25% (HR, 0.75; 95% CI, 0.59–0.96).335 A prospective cohort sugars) was associated with an increased risk of recurrence and mortality
study that included >40,000 participants also found that a healthy diet is in this same population.344 The link between red and processed meats and
associated with a lower risk for cancer (12%; 95% CI, 8%–16%; P < mortality in survivors of non-metastatic colorectal cancer has been further
.0001).336 In addition, results of randomized trials support the link between supported by recent data from the Cancer Prevention Study II Nutrition
a healthful diet and reduced incidence of cancer. For instance, results of a Cohort, in which survivors with consistently high intakes of red and
randomized controlled trial, in which 4282 women were randomly assigned processed meat had a higher risk of colorectal cancer-specific mortality
to a Mediterranean diet with olive oil, a Mediterranean diet with mixed than those with low intakes (RR, 1.79; 95% CI, 1.11–2.89).345 For survivors
nuts, or a control low-fat diet, suggest that the olive oil/Mediterranean diet of non-colorectal cancers, the evidence linking a healthy diet with better
reduced the risk of invasive breast cancer (HR, 0.32; 95% CI, 0.13– outcomes is less robust. A study of 1901 survivors of early-stage breast
0.79).337 In the Women’s Health Initiative (WHI) Dietary Modification trial, cancer found that a diet higher in fruits, vegetables, whole grains, and
nearly 49,000 postmenopausal women with a history of breast cancer and poultry and lower in red and processed meats and refined grains resulted
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in a decreased risk of overall death and death from non-breast cancer to refrain completely from alcohol consumption, because it has no proven
causes, but was not associated with risk of breast cancer recurrence or impact on outcomes, but should adhere to general population
death from breast cancer.346 recommendations.341,356,357
Unfortunately, cancer survivors often do not follow recommendations for a Currently, no consensus regarding the role of soy foods in cancer control
healthy diet and, in some studies, show worse patterns than non-cancer exists. Several large studies have found no adverse effects on breast
controls.347,348 For example, a national survey of 1533 adult cancer cancer recurrence or total mortality related to the intake of soy food.358-362
survivors and 3075 matched controls found that cancer survivors had In fact, trends towards decreased recurrence and mortality were observed.
worse dietary patterns.348 Other studies show that survivors may make The panel therefore considers moderate consumption of soy foods (≤3
improvements to their diet quality post-diagnosis.349-351 servings a day) to be prudent.
Recommendations for Nutrition in Survivors For patients desiring further recommendations for dietary guidelines, a
All survivors should be encouraged to make informed choices about food referral to a dietitian or nutritionist should be considered. The USDA
to ensure variety and an adequate nutrient intake. Recommendations for approximate food plate volumes (www.choosemyplate.gov) are:
food sources in a healthy diet are included in the guidelines. In general, a  Vegetables and fruits should comprise half the volume of food on
healthy diet is rich in plant sources, such as vegetables, fruits, whole the plate (30% vegetables; 20% fruit)
grains, legumes, olive or canola oil, avocados, seeds, and nuts. Fish and  Whole grains should comprise 30% of the plate
poultry are recommended, whereas red meats should be limited and  Protein should comprise 20% of the plate
processed meats avoided. Other processed foods and foods and Sources of dietary components:
beverages with high amounts of added sugars and/or fats should also be  Fat: plant sources such as olive or canola oil, avocados, seeds
limited. Other nutrition recommendations for survivors include eating a diet and nuts, and fatty fish
that is at least 50% plant-based, with the majority of food being  Carbohydrates: vegetables, fruits, whole grains, and legumes
vegetables, fruit, and whole grains, and tracking calorie intake. Self-  Protein: poultry, fish, legumes, low-fat dairy foods, and nuts
monitoring of caloric intake has been shown to be an effective strategy for
weight management.352,353 The use of healthy recipes, such as those found in resources such as the
ACS’s “Find Healthy Recipes” website,
In addition, survivors should be advised to avoid alcohol, or if partaking, http://www.cancer.org/healthy/eathealthygetactive/eathealthy/findhealthyre
limit alcohol intake to one drink per day for a woman and two drinks per cipes/index, should be encouraged.
day for a man.212 This is especially important for survivors of liver,
Supplement Use in Survivors
esophageal, kidney, and head and neck cancers, who should refrain from
alcohol due to an increased risk of mortality with alcohol Numerous systematic reviews and meta-analyses and a few randomized
consumption.341,354,355 Survivors of breast cancer do not need to be advised controlled trials have assessed the role of various vitamins or other dietary
supplements for the purposes of primary cancer prevention, cancer
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control, or preventing cancer recurrence.363-377 No clear evidence supports Health Behavioral Change
an effect of dietary supplements for cancer prevention, control, or Lifestyle behaviors are one area survivors can control if they are
recurrence, although a few exceptions may warrant further studies.378,379 In encouraged to change and are aware of resources to help them.
fact, a prospective cohort study of 2118 postmenopausal cancer survivors Ambivalence about changing behavior is common in the general
found that post-diagnosis dietary supplement use was associated with a population, but among cancer survivors levels of motivation are often
trend towards higher mortality among those with a poor diet.380 heightened, especially close to the time of diagnosis.205,285,391
Although the FDA regulates dietary supplement products under the Data suggest that recommendations from the oncologist can carry
Dietary Supplement Health and Education Act of 1994 (DSHEA),381 significant weight for patients with cancer, yet many providers do not
analyses of dietary supplements from multiple manufacturers have found discuss healthy lifestyle changes with survivors.285-287,392 Print materials and
that many products do not contain the purported active ingredient and can telephone counseling are other strategies that may be effective for
contain unlisted ingredients such as cheap fillers (eg, rice, house plants) improving healthy behavior in the survivor population, and several trials
or banned pharmaceutical ingredients.382,383 Furthermore, dietary show support for these strategies.289,296,304-307,326,393 In fact, a recent trial
supplements may remain available to consumers even following FDA showed that telephone-based health behavior coaching had a positive
class I drug recalls.382 effect on physical activity, diet, and BMI in survivors of colorectal
cancer.305,394 Moreover, results of the recently completed Reach Out to
Despite the lack of data supporting supplement use and the lack of
Enhance Wellness (RENEW) trial showed that an intervention of
assurance regarding supplement quality, as many as 70% to 85% of
telephone counseling and mailed materials in 641 older, obese, and
survivors take some vitamin or mineral dietary supplements, often without
overweight survivors of breast, prostate, and colorectal cancers not only
disclosing this information to their physicians.380,384-386 Thus, the panel
resulted in improved diet quality, weight loss, and physical activity but also
recommends that providers ask survivors about supplement use at regular
had a long-lasting effect that was sustained a year after the intervention
intervals.
was complete.289 The Exercise and Nutrition Routine Improving Cancer
The panel notes that supplement use is not recommended for most Health (ENRICH) intervention, which includes 6 theory-based 2-hour
survivors, except in instances of documented deficiencies (eg, survivors of sessions, has also shown a positive effect on physical activity, diet,
gastric cancer), inadequate diet, or comorbid indications (eg, weight, and BMI.395
osteoporosis,387 ophthalmologic disorders,388 cirrhosis389,390). Survivors
Another strategy, motivational interviewing, may be an effective technique
should be advised that taking vitamin supplements does not replace the
for increasing physical activity and other healthy behaviors in cancer
need for adhering to a healthy diet. If deemed necessary (eg, for survivors
survivors.302,303 Motivational interviewing focuses on exploring the
taking multiple and/or or unfamiliar supplements), referral to a registered
survivor’s thoughts, wants, and feelings and is directed at moving
dietitian, especially a CSO, should be considered for guidance in
ambivalence so survivors choose to change their behavior.396 Other
supplement use.
behavioral strategies may also be useful, such as improving self-efficacy
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(ie, the belief that one can perform the actions of new activity and maintain Risk Assessment and Screening for Immunizations and Prevention of
this practice by addressing barriers and planning for behavior change) and Infections
self-monitoring.397,398 Clinicians can consider referral to a provider trained Survivors are at elevated risk for infections if their cancer treatment
in the techniques of motivational interviewing. included chemotherapy, monoclonal antibodies (eg, rituximab,
alemtuzumab), radiation, corticosteroids, splenectomy, CAR T-cell
Immunizations and Prevention of Infections therapy, and/or HCT (which includes peripheral blood stem cell
Cancer survivors are at elevated risk for infection because of immune transplantation, bone marrow transplantation, and cord blood
suppression associated with previous cancer treatments, such as transplantation). Risk is also elevated if the survivor has prior or current
chemotherapy, radiation, corticosteroids, certain surgeries, and stem cell exposure to endemic infections or epidemics, or has a history of blood
transplantation. In fact, antibody titers to vaccine-preventable diseases transfusion.
decrease after anti-cancer treatment.399,400 In addition, survivors are at
Interventions for Prevention of Infections
increased risk of complications from vaccine-preventable diseases, such
Infection in survivors can be prevented by education, antimicrobial
as those caused by HPV and influenza viruses.400,401
prophylaxis, and the judicious use of vaccines. For information regarding
Many infections in survivors can be prevented by the use of vaccines. antimicrobial prophylaxis, please see the NCCN Guidelines for Prevention
However, data from the BRFSS found that 42% of survivors did not and Treatment of Cancer-Related Infections (available online at
receive an influenza vaccination in 2009, and 52% reported never www.NCCN.org).
receiving a pneumococcal vaccination.183 Analysis of the SEER-Medicare
Education
database showed that survivors of breast cancer, aged ≥65 years, were
Survivors should be educated about safe pet care, the avoidance of
less likely to receive an influenza vaccination than matched non-cancer
zoonosis, travel precautions, gardening precautions, proper hand hygiene,
controls.141 A separate analysis of the SEER-Medicare database by
and avoidance of respiratory droplets during a respiratory virus
another group found similar results.402
pandemic.406-413 Contact with pets did not increase the risk of fever,
Vaccines represent a unique challenge in cancer and transplant survivors, bacteremia, pneumonia, and gastroenteritis in children with acute myeloid
because they may or may not trigger the desired protective immune leukemia (AML),414 and the panel believes that contact with pets is
responses due to possible residual immune deficits.403-405 In addition, generally safe for most survivors. However, survivors should wash hands
certain vaccines, such as those that are live attenuated (eg, zoster [ZVL, with soap and running water after handling animal feces. If possible,
MMRV, or VAR]; MMR), are contraindicated in actively survivors at high risk for immune suppression should avoid direct contact
immunosuppressed survivors because of an increased risk of developing with animal feces and other bodily secretions. Survivors with elevated risk
the disease and/or prolonged shedding of the live organism given in the of infection and those who are immunocompromised are at higher risk for
vaccine. zoonoses and should use extra caution and avoid contact with exotic
animals (ie, snakes, turtles). Travel precautions include education on the
need for pre-travel vaccines, prophylaxis against specific infections, and
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education on how to prevent waterborne, airborne, and zoonotic Before vaccination, immune system viability and history of allergic
infections.415 Travelers may find useful information at reactions to vaccines should be assessed. Baseline white blood cell
https://wwwnc.cdc.gov/travel/yellowbook/2018/advising-travelers-with- (WBC) counts should be in the normal range or within reasonable limits
specific-needs/immunocompromised-travelers or by consulting a travel before starting vaccinations, unless they are elevated because of disease
clinic. Gardening precautions include wearing gloves to avoid cuts and status. The survivor should not be on immunosuppressive drugs or
punctures that could be delayed in healing or become infected with fungus chemotherapy, and ongoing infection should not be present.
or staphylococcus/streptococcus that may be present on thorns, and
wearing a protective mask to avoid inhalation of spores. The following vaccines should be considered and encouraged for all
survivors, and administered according to the usual doses and schedules:
Immunizations influenza vaccine (only inactivated or recombinant); tetanus, diphtheria,
Vaccination, or “active immunization,” involves administration of all or part pertussis; recombinant zoster vaccine (RZV) in all survivors ≥50 years;
of a microorganism or a modified product of a microorganism (eg, a toxoid, and HPV in previously unvaccinated survivors through age 45 years.416
a purified antigen, an antigen produced by genetic engineering) to produce These vaccines do not contain live organisms; instead, they contain
an immunologic response that mimics that of natural infection but usually inactivated organisms, purified antigens, bacterial components, or
presents little or no risk to the recipient. The use of vaccines that do not genetically engineered recombinant antigens. Whereas the effectiveness
contain live organisms should be considered and encouraged in all cancer of these vaccinations might be suboptimal because of lingering immune
and transplant survivors who have completed immune-suppressive suppression,405 their administration is likely worthwhile to achieve some
therapy (ie, chemotherapy or antibody-based therapy) at least 3 months protection in the absence of known harm.
prior to the planned vaccination. Patients receiving anti-estrogen or other
Pneumococcal vaccine (PPSV-23/PCV-13) is recommended for all adults
hormone-modulating therapy do not have to delay vaccination for the
aged ≥65 years and those at any age with immunocompromising
completion of therapy. In general, the usual doses and schedules are
conditions.418,419 Pneumococcal vaccination is also recommended for
recommended, as outlined by the Advisory Committee on Immunization
Practices (ACIP).416 The Infectious Diseases Society of America (IDSA) survivors of lung cancer and those who had lung resection. Data from a
population-based matched cohort study in Taiwan found that
has outlined guidance for vaccination in immunocompromised patients,
including those with cancer and those post-HCT.417 The NCCN administration of PPSV-23 to ≥5-year survivors of cancer reduced
hospitalization for pneumonia.420 Other vaccines, as listed in the
Survivorship Panel outlined immunization guidelines specific to survivors
guidelines, should be considered in consultation with an infectious disease
of hematologic malignancies and solid tumors, with separate guidelines for
or travel medicine specialist if unique circumstances in the survivor’s
survivors who have received cellular therapies (ie, CAR T-cell therapy,
lifestyle, upcoming travel, functional or anatomic asplenia, or local
HCT). In survivors who received anti–B-cell antibody therapy, vaccination
should be delayed for at least 6 months after chemotherapy or the last epidemic/risks merit their use.
dose of such therapy to allow for reconstitution of the B-cell population.
More details are available in the guidelines.
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Live Viral Vaccines Influenza Vaccines

Vaccines that contain live attenuated organisms (eg, live-attenuated Annual influenza vaccination is recommended for all cancer and transplant
influenza vaccine; MMR; ZVL; VAR; yellow fever vaccine) are survivors.421 Live attenuated influenza vaccines should be avoided in some
contraindicated in actively immunocompromised survivors because of a survivors (see Live Viral Vaccines, above).422,423 Therefore, preferred
proven or theoretical increased risk of disease and prolonged shedding of vaccines include inactivated influenza vaccines (ie, trivalent [IIV3]
the live organism present in the vaccine. They should not be offered to standard-dose, trivalent [IIV3] high-dose, and quadrivalent [IIV4] standard-
actively immunocompromised survivors, unless cleared by a clinician dose) or recombinant influenza vaccine (ie, trivalent [RIV3] or quadrivalent
experienced in vaccine use or by an infectious disease specialist. [RIV4]).416,422,423 Some evidence suggests that the high-dose IIV3 vaccine
may provide better protection than standard-dose IIV3 in individuals 65
Live viral vaccines can be administered, however, to immunocompetent years or older.424 No studies have addressed the superiority of any
survivors 3 or more months after chemotherapy or 6 or more months after influenza vaccine in the cancer survivor population specifically.
anti–B-cell antibody therapy, although consultation with an infectious Administration of the influenza vaccine to survivors with egg allergy
disease specialist or clinician familiar with vaccination in patients with symptoms (other than hives) should be done at a center that can manage
cancer is strongly recommended. Live viral vaccines should not be severe allergic reactions, as currently recommended for all individuals.425
administered to survivors who had cellular therapies (ie, CAR T-cell
therapy, HCT) with active graft-versus-host disease (GVHD) or ongoing Zoster (Shingles) Vaccine
immunosuppression. They should only be administered to HCT survivors A new recombinant zoster vaccine (RZV) has become available in the
without active GVHD or ongoing immunosuppression following United States. The recombinant vaccine is the preferred zoster vaccine for
consultation with an infectious diseases specialist. For all survivors, when cancer survivors, and is recommended for survivors aged ≥50 years.426
other vaccine options exist, they are preferred over live-attenuated Studies have shown it to be safe and effective in survivor populations.427,428
vaccines (eg, RZV). In survivors who have previously received the live-attenuated zoster
vaccine, immunization with RZV should be considered. The recombinant
Healthy immunocompetent individuals who live in a household with
vaccine should not be given sooner than 2 months after administration of
immunocompromised survivors can receive the following live vaccines
the live attenuated vaccine.
with caution: MMR, varicella zoster (VAR, MMRV, or ZVL), yellow fever,
rotavirus, and oral typhoid vaccines.417 Immunocompromised survivors If RZV is unavailable or access to it is an issue, live zoster vaccine can be
should avoid contact with persons who develop skin lesions after receipt of given as a single dose to survivors aged ≥60 years without active or
varicella zoster vaccination until the lesions clear. In addition, ongoing immunodeficiency, no history of cellular immunodeficiency or
immunocompromised survivors should avoid handling diapers of children HCT, and who have not received chemotherapy or radiation within the
who have been vaccinated with rotavirus vaccine for 4 weeks after past 3 months, or it can be given at least 4 weeks before initiation of
vaccination. chemotherapy or immunosuppressive drugs.417,429 Live zoster vaccine can
also be considered for survivors aged 50 to 59 years with a history of
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varicella zoster virus (VZV) infection or VZV seropositivity with no previous signaling pathway inhibitors, cisplatin, anthracyclines with or without
doses of VAR vaccine if the recombinant vaccine is unavailable. Live taxanes, androgen deprivation therapy [ADT]) and radiation therapy are
zoster vaccine should be avoided in immunocompromised survivors, but associated with cardiovascular toxicities and can result in diverse
VAR can be considered in transplant survivors without active GVHD or cardiovascular issues, including cardiomyopathy, hypertension,
enhanced immunosuppression 24 or more months after transplantation. hyperlipidemia, cardiac arrhythmia, myocardial infarction, and
cerebrovascular accidents.436-444 In addition, shared risk factors for both
Recommendations for Specific Effects of Cancer and Its cancer and CVD likely contribute to the development of CVD and
Treatment structural heart disease or heart failure in cancer survivors. These risk
Randomized controlled trials have provided evidence for the effectiveness factors include well-established and well-studied risk factors such as
of interventions for cancer survivors to lessen symptoms such as tobacco use, obesity, and poor health behaviors, as well as recently
depression, fatigue, pain, sleep disorders, and sexual dysfunction.179 The discovered ones. For example, somatic mutations in blood cells cause
NCCN Survivorship Panel used such evidence as the basis for the clonal hematopoiesis of indeterminate potential (CHIP) and increase the
recommendations in these guidelines. When evidence in survivorship risk of hematologic malignancies; CHIP is also emerging to be an
populations was lacking, extrapolation from other populations was used as important causal risk factor for CVD.445 Other well-defined CVD risk factors
deemed appropriate. The panel also evaluated existing guidelines from (eg, hypertension, hyperlipidemia, diabetes) are more common in cancer
other organizations as appropriate when making recommendations. than non-cancer populations.446,447 Most CVDs (eg, atherosclerosis)
Otherwise, expert opinion and panel consensus was used to form develop over time as a result of these and other risk factors. Thus, the risk
recommendations. These recommendations and their evidence base are of CVD-related death varies with years from cancer diagnosis, with most
discussed below. The panel also notes that referral to other health care survivors being at greatest risk 5 or more years after diagnosis and
disciplines/providers or community resources may be used to address completion of curative therapy.448
several indications or identified issues with one intervention (eg,
rehabilitation for fatigue, depression, and pain). Control of CVD and shared CVD/cancer risk factors can decrease the risk
of subsequent cardiovascular events.448,449 Data show that attention to and
Cardiovascular Disease Risk Assessment counseling about CVD/cancer risk factors may improve cancer- and
CVD and cancer are the two leading causes of death in the United States, cardiovascular-related outcomes. 450 However, data also show that fewer
together accounting for approximately 44% of deaths in 2017.430 CVD is than half of cancer survivors discuss diet, exercise, or smoking or other
also a leading cause of death in cancer survivors; for survivors of most lifestyle changes with their physician.287,446
cancer types, it is the most common cause of non-cancer death.431 In fact,
Tools exist to help quantify atherosclerotic CVD risk (eg, ASCVD risk
survivors of most cancers have a markedly increased risk of developing
score451), but these tools do not take into account cancer treatment history
CVD compared with non-cancer populations.432-435 One reason for this
(eg, anthracycline or tyrosine kinase inhibitor [TKI] exposure) and thus
increased CVD risk in cancer survivors is that cytotoxic, hormonal, and
may not accurately capture true CVD risk in a given survivor.
targeted systemic cancer therapies (eg, HER2-directed therapy, VEGF
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The panel recommends that physicians provide CVD risk assessment and Anthracycline-Induced Cardiac Toxicity
counseling on CVD risk factor management to all cancer survivors Many cancer treatments, including chemotherapeutics, targeted agents,
throughout the survivorship continuum. The assessment should include: 1) hormonal therapies, and radiation, are associated with cardiovascular
pre-existing and emerging CVD including CAD, CHF, peripheral vascular toxicities.436-442 Cardiovascular sequelae can include arrhythmias,
disease, and arrhythmias including atrial fibrillation; 2) CVD risk factors pericardial disease, hypertension, thrombosis, cardiomyopathy/heart
including hypertension, dyslipidemia, obesity, cigarette/tobacco use, and failure, and vascular and metabolic issues. Survivors of some cancer
diabetes mellitus; 3) cancer treatment history including systemic therapy types have a markedly increased risk of developing CVD compared with
regimen and radiation field, including cumulative doses received of non-cancer populations.432-434 As a result, a new field, called “Cardio-
applicable cardiotoxic therapies; and 4) diet and exercise habits and Oncology,” focused on the cardiovascular health of patients with cancer
cigarette/tobacco use. The counseling should include discussions of any and survivors has become established.448,454
increased risk of CVD the survivor may have based on prior cancer
treatment, comorbidity, or CVD risk factors and on the ABCDE's of CVD Anthracyclines (eg, doxorubicin, epirubicin, daunorubicin) are used to treat
Prevention. Interventions for modifiable risk factors should be many cancer types, including lymphoma, sarcoma, and breast cancer, and
recommended as appropriate. Cooperation and shared care with primary are among the best-studied and most common causes of cancer
care providers, and with cardiovascular specialists as needed, is key to treatment-induced cardiac injury.455-457 The mechanism by which
optimizing cardiac and vascular outcomes in cancer survivors. Referral to anthracyclines cause cardiomyopathy is not fully understood, but likely
cardio-oncology or a cardiology specialist should be considered for cancer involves the formation of reactive oxygen species (ROS), oxidative injury,
survivors deemed to be at high risk for the development of CVD. and the subsequent induction of apoptosis in cardiac cells.458 A role for
topoisomerase-IIβ in cardiomyocytes in the production of ROS in response
The ABCDEs to Promote Cardiovascular Wellness in Cancer Survivors to anthracyclines has been suggested.459
table in the Guidelines above was adapted from a paradigm developed to
address CVD risk factors in survivors of breast and prostate cancer.452,453 Studies suggest that the incidence of clinical CHF after anthracycline-
The table includes items such as aspirin use for secondary prevention based therapy for adult-onset cancer is <5%.460-463 For instance, in the
(with clinician-survivor discussion required for primary prevention with NSABP B-31 trial of patients with breast cancer, the rates of symptomatic
careful weighing of benefits and risks), blood pressure heart failure after 7 years were 4% in patients treated with anthracycline-
monitoring/management, cholesterol assessment/management, healthy based chemotherapy and trastuzumab and 1.3% in those treated with
lifestyle recommendations including diet/weight management and anthracycline-based chemotherapy alone.462 However, a significantly
exercise, and an echocardiogram (ECHO) and/or electrocardiogram higher percentage of patients have evidence of subclinical heart failure
(ECG) based on individual risk. with reports of asymptomatic left ventricular ejection fraction (LVEF)
decline being 9% to 50% in various studies.460,464-466
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The panel has focused specifically on anthracycline-induced cardiac increased to the baseline value), and 71% had partial recovery (LVEF
toxicity in these guidelines. Other systemic therapies (eg, HER2-targeted increased by >5 absolute points and reached >50%). In addition, a
agents, angiogenesis inhibitors, immunotherapies) may cause growing body of preclinical, observational, and pilot research suggests that
cardiomyopathy or other myopathies like myocarditis,437,467,468 and the lifestyle changes, such as weight control,474-476 dietary modification (either
panel acknowledges that some of the concepts presented in these through correcting dietary deficiencies or increasing intake of various
recommendations may apply to these other cardiomyopathies. However, it nutrients),477 and exercise,220,221,478-480 may also be helpful at these early
is important to note that fewer data are available on the cardiomyopathies stages, prior to the onset of heart failure symptoms, although more
associated with non-anthracycline systemic therapies and that these research is necessary.481,482
cardiomyopathies may differ in nature from those induced by
anthracyclines.437 More research is needed to understand the specific These emerging issues in anthracycline-induced cardiomyopathy are
mechanisms of cardiomyopathies associated with newer agents. In consistent with the changes in the cardiology community’s approach to
addition, the panel emphasizes that the approach to cardiomyopathy may heart failure at large. Clinical heart failure has established risk factors, and
be different than the approach to other cardiac diseases such as CAD, the earliest signs of heart failure begin with the accumulation of these risk
which could occur, for example, as a result of radiation therapy.469 factors over time, ultimately resulting in structural cardiac abnormalities
and later symptomatic heart failure. As a result, more than a decade ago,
Panel Considerations Regarding Anthracycline-Induced Cardiac Toxicity this evolutionary and progressive nature of heart failure was recognized by
Anthracycline-induced heart failure may take years or decades to cardiologists and incorporated into the American Heart Association
manifest. Previous dogma has suggested that anthracycline-induced heart (AHA)/American College of Cardiology (ACC) Guidelines for the
failure portends poor prognosis and is not responsive to therapy. However, Evaluation and Management of Heart Failure.483 In 2001, the AHA/ACC
emerging data in heart failure due to other types of cardiac injury suggest guidelines proposed a new classification for heart failure.483 Traditional
that signs of cardiac dysfunction can be seen early, prior to the classifications only recognized heart failure when patients presented with
development of symptoms.470 Additionally, data from these other types of clinical signs and symptoms. The 2001 classification scheme, in contrast,
cardiac injury suggest that early intervention with cardioprotective introduced stages of heart failure beginning before the patient is
medications results in better long-term cardiac function.471,472 It is possible symptomatic, and emphasized the importance of prevention in heart
that if anthracycline-induced cardiac dysfunction is detected early, it may failure management.
also be responsive to cardioprotective medications.437,470-473 In fact, data
from a prospective study that followed 2625 patients who received The panel believes that this revised AHA/ACC classification is particularly
anthracycline-containing therapy through the survivorship phase suggest relevant to cardio-oncology populations. Therefore, in formulating the
that early initiation of heart failure therapy may allow for at least partial present recommendations for screening, evaluation, and treatment of
recovery of LVEF in this population.464 In this study, survivors were started cardiac dysfunction in survivors who received anthracyclines during their
on treatment when LVEF decreased by >10 absolute points and was cancer treatment, the panel took into consideration the updated AHA/ACC
<50%. A full recovery was observed in 11% of treated survivors (LVEF classification and guidelines for management of heart failure. For these
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Survivorship
NCCN Guidelines for Survivorship, the panel emphasized early may be decreased cardiac contractility, which can result in decreased
recognition of cardiac toxicity with the goal of preventing the development LVEF (also Stage B). Cardiac remodeling generally precedes the
of clinical, symptomatic heart failure by addressing other known risk development of symptoms (by months or even years), continues after
factors for heart failure. In particular, appropriate use of cardioprotective symptoms become evident, and contributes substantially to symptom
medications, such as neurohormonal antagonists (ie, angiotensin- progression and mortality despite treatment. Individuals are considered to
converting enzyme [ACE] inhibitors, beta-blockers), can be considered have Stage C heart failure when clinical signs and symptoms accompany
with the goal of preventing cardiac remodeling over time in some patients. structural changes to the heart. Stage D is the most advanced stage, with
In this respect, the panel emphasizes a thorough clinical screen for heart patients showing advanced structural heart disease and significant heart
failure for all survivors with exposure to anthracyclines after completion of failure symptoms at rest that are refractory to medical therapy; these
therapy, with the additional consideration of an echocardiographic screen patients require specialized interventions.
in high-risk survivors, as discussed in more detail below. The panel also
believes that early involvement of a cardio-oncologist or cardiologist in the The panel also considered the New York Heart Association’s (NYHA)
care of the cancer survivor is important. Therefore, there should be a low functional classification of heart failure.485 In this system, which is based on
threshold for referral to a cardio-oncologist or cardiologist. In addition, limitations to physical activity and the effect of physical activity on heart
symptoms of heart failure may mimic other conditions such as pulmonary failure symptoms, NYHA Class I is similar to AHA/ACC Stage B, while
issues and/or cardiac ischemia; therefore, a global approach may be NYHA Class II and III would be considered AHA/ACC Stage C and NYHA
necessary when assessing survivors with decreased cardiorespiratory Class IV is similar to AHA/ACC Stage D.
fitness.484
Assessment for Anthracycline-Induced Cardiac Toxicity
Classification of the Stages of Heart Failure The panel recognizes a lack of high-quality data to inform the benefits of
The revised AHA/ACC classification identifies patients who do not have screening for heart failure among patients treated with anthracyclines.
symptoms associated with heart failure but are either at risk for heart However, the panel believes that all survivors who have completed
failure (Stage A) or have structural abnormalities of the heart (Stage B).483 anthracycline therapy should undergo a clinical evaluation to assess for
This revised classification has both diagnostic and therapeutic utility, signs and symptoms of heart failure. The lack of data is illustrated in a
because evidence suggests that treatments prescribed in the absence of 2007 clinical evidence review by ASCO, which concluded that no studies
structural heart abnormalities or symptoms can reduce the morbidity and had systematically addressed the benefits of screening adult cancer
mortality of heart failure in the general population.437,464,470-473 Left untreated, survivors with a history of anthracyclines for cardiotoxicity.486 The review
however, the accumulation of cardiac risk factors leads to injury or stress also found no direct evidence showing the effectiveness of cardiac
on the myocardium and generates a cascade of signaling events in the treatment on outcomes of asymptomatic survivors.486 A 2008
heart. The subsequent change in the geometry and structure of the left multidisciplinary task force from the Children’s Oncology Group came to
ventricle, often referred to as cardiac remodeling (Stage B), may manifest largely similar conclusions regarding screening for cardiotoxicity in
as cardiac hypertrophy or chamber dilatation. In other cases, the result survivors of pediatric cancers.487 Some reasons for the lack of data on
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Survivorship
screening survivors for cardiotoxicity have been discussed,488 and, treatment, including survivors with a history of anthracycline therapy.
unfortunately, high-quality data have not been forthcoming since ASCO’s Insufficient evidence prevented the ASCO panel from making a
2007 review. recommendation regarding the frequency and duration of additional
surveillance of survivors who are asymptomatic and who showed no signs
In the absence of data, the Children’s Oncology Group relied on the of cardiac dysfunction on initial assessment.
collective clinical experience of its panel members and recommended
echocardiograms or comparable imaging to evaluate cardiac anatomy and The NCCN Survivorship Panel defined its screening recommendations
function for survivors of pediatric cancer at the conclusion of treatment and based largely on consensus and on the idea that early recognition and
then every 1 to 5 years for life depending on age at treatment, treatment of cardiotoxicity can allow for earlier interventions that may
anthracycline dose, and chest irradiation improve prognosis (discussed below).
(http://www.survivorshipguidelines.org). An international collaborative
supports lifelong echocardiographic surveillance at least every 5 years in Assessment for Symptoms of Heart Failure
survivors of childhood cancer treated with anthracyclines.489 Although the According to the 2013 AHA/ACC guidelines, the cardinal manifestations of
frequency of cardiac assessment using echocardiograms or multigated clinical heart failure (Stage C) include dyspnea and fatigue (which may
acquisition (MUGA) scans in this population has been a matter of debate, lead to limited exercise tolerance) or fluid retention (which may lead to
there is general support for at least one assessment in children who have pulmonary and peripheral edema).494 These symptoms can lead to
completed anthracycline therapy.490,491 decreased functional capacity and affect quality of life. Heart failure
symptoms associated with fluid retention may also include orthopnea or
A 2014 joint expert consensus statement from the American Society of paroxysmal nocturnal dyspnea. Therefore, the panel recommends a
Echocardiography and the European Association of Cardiovascular history and physical to look for these symptoms to help identify survivors
Imaging recommends yearly cardiovascular assessment of adult survivors who might already be symptomatic. These survivors should undergo
after the completion of potentially cardiotoxic therapy to look for early evaluation with an echocardiogram. If no evidence of structural heart
signs and symptoms of CVD, with cardiac imaging used at the discretion disease is seen, then a workup for other causes of the symptoms is
of the clinician.492 The groups recommend echocardiogram as the warranted with referral to other specialties (eg, pulmonology or cardiology)
preferred imaging modality, when imaging is performed. The report also as needed. Symptomatic survivors with evidence of structural heart
acknowledged the limited data available to inform their recommendations. disease require immediate referral to a cardio-oncologist or cardiologist.
In 2017, ASCO released a clinical practice guideline for the prevention and Assessment of Comorbidities and Cardiovascular Risk Factors
monitoring of cardiac dysfunction in survivors of adult cancers.493 The The panel recommends assessment of comorbidities and other traditional
ASCO panel gave a moderate-strength recommendation (as based on risk factors for heart disease (see Cardiovascular Disease Risk
evidence and the balance between harms and benefits) that Assessment, above). Furthermore, the oncologic history of the survivor
echocardiogram can be performed for asymptomatic survivors deemed to should be reviewed. Chest radiation can increase the risk of ischemic
be at increased risk for cardiac dysfunction at 6 to 12 months after
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Survivorship
cardiac disease, which can contribute to heart failure.436,442,448,495 The trial, cardiac function was assessed by cardiac imaging in patients after
addition of other cardiotoxic therapies (eg, HER2-targeted agents) to initial anthracycline-based therapy as a requirement for further treatment
anthracyclines can further increase the risk of heart failure over that seen with trastuzumab.501 Over 7% of patients experienced cardiac symptoms
with the use of anthracyclines alone.496 Older survivors, those with a higher and/or a decrease in LVEF of >15% after receiving anthracyclines, thus
cumulative anthracycline dose (cumulative doxorubicin dose of 250 mg/m2 excluding them from being considered for trastuzumab. It is important to
or equivalent497), those with underlying CVD or risk factors, and those who note that this was a clinical trial patient population without significant
had a low-normal (50%–54%) baseline ejection fraction are also at cardiac risk factors or history of cardiac disease. In a non-clinical trial
increased risk for the development of heart failure. Recent data also population of patients with cancer, many may already have cardiac risk
showed that being overweight or obese and visceral and intramuscular factors or actual cardiomyopathy prior to treatment, thus elevating the risk
adiposity are risk factors for cardiotoxicity from anthracyclines in breast of developing heart failure. Together, these results indicate that a
cancer survivors.498,499 In addition, the risk of cardiac events and death in significant proportion of survivors with early-onset Stage B or greater heart
survivors of breast cancer has been shown to increase as the number of failure can be identified with appropriate imaging after therapy. However, it
cardiovascular risk factors increases.500 is not clear that these declines in LVEF after anthracycline therapy were
associated with an increased risk of developing subsequent heart failure.
Imaging
When developing these imaging guidelines for screening for cardiac Regarding the second question, little is known regarding the natural
toxicity in survivors with a history of anthracycline exposure, the panel history of heart failure in survivors with Stage B heart failure post-
considered several questions: 1) Is the prevalence of structural heart anthracycline therapy, and the long-term prognosis of survivors with
disease high enough to warrant screening of anthracycline-treated cardiac structural abnormalities following anthracycline exposure is not
survivors?; 2) Is an abnormal echocardiogram post-anthracycline therapy known. However, regarding the final question, limited evidence suggests
associated with an increased risk for the future development of that further remodeling of the heart may be able to be mitigated by
symptomatic heart failure?; and 3) Does the recognition of cardiac initiation of cardioprotective medications. A number of observational and
abnormalities and treatment of cardiac risk factors post-anthracycline retrospective studies have suggested that early intervention with
therapy affect outcomes? cardioprotective medication may decrease the rate of cardiac remodeling
and progression to heart failure. A randomized controlled trial of 135
As for the prevalence of structural heart disease in patients treated with survivors of pediatric cancer with ≥1 cardiac abnormality found that the
anthracyclines, a study of 2625 patients with cancer (mostly breast cancer angiotensin-converting enzyme (ACE) inhibitor enalapril reduced left
or non-Hodgkin lymphoma) assessed LVEF before, every 3 months during ventricular end-systolic wall stress compared to placebo (P = .03).473 The
anthracycline chemotherapy and during the following year, every 6 months authors concluded that any theoretical benefit of reduced left ventricular
for the next 4 years, and annual after that.464 Cardiotoxicity, defined as end-systolic wall stress must be weighed against the side effects of
LVEF <50% and decreased by >10 absolute points, was observed in 9% treatment; dizziness or hypotension was observed in 22% of the treatment
of the study population. In the large randomized controlled NSABP B-31 group versus 3% of those receiving placebo (P = .0003), and fatigue was
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Survivorship
observed in 10% versus 0% (P = .013) of participants. More recently, a types (see the NCCN Guidelines for Treatment of Cancer by Site, at
review of 247 patients with cancer and declines in LVEF at the Stanford www.NCCN.org, for specific monitoring recommendations).
cardiology clinic found that mean LVEF increased after treatment (most
often with ACE inhibitors and beta-blockers) and rose to ≥50% in 77% of The panel recommends two-dimensional echocardiogram, coupled with
patients.472 In addition, a study of 201 adult patients with cancer, who were Doppler flow studies, as the cardiac imaging modality of choice when
treated with anthracyclines and had an LVEF of ≤45%, found that earlier imaging is performed. This technique is widely available and inexpensive,
initiation of enalapril (and sometimes the beta-blocker carvedilol) was gives no radiation exposure, and is the most useful diagnostic test in the
associated with a higher likelihood of LVEF recovery.470 In addition, in the evaluation of patients with possible heart failure.502,503 It can recognize
larger study by this group (2625 patients), heart failure therapy was early stages of heart failure by revealing abnormalities of the pericardium,
initiated in all patients with LVEF <50% that had decreased by >10 myocardium, and heart valves.494 While radionuclide ventriculography
absolute points, and 82% of patients experienced a full or partial (also called radionuclide angiography or MUGA scan) can provide
recovery.464 In the non-cancer setting, a randomized controlled trial of accurate measurements of left ventricular size and function and
>4200 participants found that treatment of patients with asymptomatic left assessment of ventricular enlargement, it cannot assess valvular
ventricular dysfunction (ejection fraction ≤35%) with enalapril reduced the abnormalities or cardiac hypertrophy and exposes patients to radiation.
incidence of heart failure compared with placebo (20.7% vs. 30.2%; P < Other imaging modalities for the assessment of heart failure have been
.001).471 reviewed elsewhere.502,504
Considering these data, the panel believes that survivors with a high In agreement with these guidelines, ASCO’s guidelines that address
cumulative anthracycline dose (ie, cumulative doxorubicin dose ≥250 monitoring of cardiac toxicity after treatment in survivors of adult-onset
mg/m2 or equivalent) or a low cumulative anthracycline dose and 1 or cancer indicate that echocardiogram can be considered for asymptomatic
more heart failure risk factors (ie, hypertension, dyslipidemia, diabetes survivors deemed to be at increased risk for cardiac dysfunction, including
mellitus, family history of cardiomyopathy, age >65 years, low-normal survivors with a history of anthracycline therapy.493
baseline LVEF [50%–54%], history of other cardiovascular comorbidities
Biomarkers
[atrial fibrillation, known CAD, baseline evidence of structural heart
The panel recognizes the growing body of literature suggesting the
disease], smoking, obesity) can be considered for assessment for
possible utility of cardiac biomarkers (specifically troponin) as a non-
structural heart disease with appropriate cardiac imaging within 12 months
invasive marker of cardiotoxicity. The panel believes that more
of the last anthracycline dose. In one study with a median follow-up of 5.2
prospective, multi-institutional studies are needed, but that biomarker use
years, 98% of cases of cardiotoxicity were observed within the first year
can be considered in select patients at high risk for heart failure. The
after treatment.464 The prevalence of late-onset cardiotoxicity has not been
optimal timing of troponin assessment in relation to completion of
well studied beyond 5 years, but the panel acknowledges that longer-term
chemotherapy is currently unclear, the cut-off point for a positive test is
cardiovascular surveillance may be needed for survivors of certain cancer
undefined, and the optimal assay platform remains to be determined. In
addition, the sensitivity and specificity of troponin I levels for predicting
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cardiotoxicity are fairly low, reported at 48% (95% CI, 0.27–0.69) and 73% hypertension, CAD, diabetes mellitus, a family history of heart failure, or a
(95% CI, 0.59–0.84), respectively.505 A systematic review of the role of history of cardiotoxins such as anthracyclines. Therefore, all survivors with
post-treatment cardiac troponins as predictive markers of anthracycline- exposure to anthracyclines have, by definition, at least one risk factor that
induced left ventricular dysfunction revealed few studies and inconsistent predisposes them to cardiac disease and should be treated as
data.506 The utility of other potential cardiac biomarkers has been reviewed appropriate. Other anti-cancer systemic therapies are potentially
elsewhere.504 cardiotoxic and may increase the risk of cardiac disease.439 Involvement of
the survivor’s PCP in the management of survivors with cardiac risk
Treatment of Anthracycline-Induced Cardiac Toxicity
factors is encouraged. Management can include addressing underlying
Progression of heart failure is accelerated with accumulation of risk risk factors, recommending physical activity and healthy dietary habits,
factors. Injury or stress on the myocardium (such as during and after and referral to a cardiologist.
treatment with anthracyclines) can lead to activation of endogenous
neurohormonal systems, which play a critical role in cardiac remodeling Treatment of Stages B, C, and D Heart Failure
and therefore progression to Stage B heart failure. The panel recommends referral to a cardiologist for all survivors with
Stages B, C, or D heart failure. The sooner treatment is initiated, the more
The panel recommends that heart failure risk factors, including
likely it is to be successful.470
hypertension, obesity, metabolic syndrome, and diabetes, be addressed in
all survivors who have completed anthracycline therapy. In addition, Anxiety, Depression, Trauma, and Distress
survivors with a history of anthracycline therapy should be advised to
Cancer survivors are at elevated risk for anxiety, depression, and other
engage in regular physical activity, eat a healthy diet, and avoid behaviors
forms of psychosocial distress and mental health concerns. A large
that may increase the risk of heart failure or CVD (eg, cigarette/tobacco or
nationwide matched cohort study in Sweden found that mental health
illicit drug use). Physical activity has been shown to improve control of
disorders can persist in survivors for as long as 10 years post-diagnosis.508
hypertension and to slow cardiac remodeling in breast cancer survivors
Unfortunately, the majority of community-based physicians report
with heart failure.507 Involvement of the survivor’s primary care provider in
insufficient psycho-oncology services and difficulty in the referral process,
managing risk factors is encouraged.
such that psycho-oncology needs often do not receive the attention they
The panel recommends that a low threshold be established for referral to a need.509
cardio-oncologist or cardiologist for all patients previously treated with an
Many cancer survivors do not have psychiatric clinical diagnoses but still
anthracycline. Additional recommendations for each stage of heart failure
have symptoms that can have a negative impact on quality of life and
are discussed below.
require further evaluation and intervention. Such survivors have what the
NCCN Guidelines for Distress Management (available at www.NCCN.org)
Treatment of Stage A Heart Failure
define as distress: “a multifactorial unpleasant experience of a
Stage A heart failure recognizes several well-established risk factors, each
psychological (ie, cognitive, behavioral, emotional), social, spiritual, and/or
of which contribute to early stages of heart failure. These include
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physical nature that may interfere with one’s ability to cope effectively with be 1.66 (95% CI, 1.09–2.53).524 In one longitudinal study, 12% of survivors
cancer, its physical symptoms, and its treatment.” Distress, often related to reported that their PTSD symptoms resolved over 5 years, whereas 37%
fear of recurrence, is common in survivors and can negatively impact reported that their symptoms persisted or worsened during that time.75
quality of life.19,69,510-512 Survivors with untreated, uncontrolled emotional Another study found that 22% of survivors had PTSD symptoms at 6
distress are less likely to adhere to recommended surveillance and are months, and 6% had such symptoms at 4 years.525 PTSD symptoms in
less likely to engage in health-promoting activities, such as exercise and survivors can fluctuate over time, because of other events or trauma
smoking cessation.120 Sometimes these individuals develop thoughts of occurring in the survivor’s life.
ending their lives; the incidence of completed suicide among patients with
cancer and survivors in the United States is about twice that of the general The panel’s recommendations for the management of anxiety, depression,
population.513-518 and distress in survivors adhere to the following general structure: screen
regularly, refer those with needs beyond the clinician’s scope of expertise,
Risk factors for psychosocial distress in cancer survivors include and ensure the safety of the survivor. Referral to mental health services
persistent problems with physical health; enduring physical signs of may include a psychiatrist, psychologist, advanced practice clinicians,
cancer/negative body image; a tendency towards self-criticism; non-white and/or social worker, or management with oncology or primary care
race; low educational, financial, or social support; financial concerns; support and online, telephone-based, or community support resources.
being unmarried; and having survived multiple primary cancers.519 Therapists with psycho-oncology training are preferred if available;
therefore, distance-based methods may be needed for those without
Fear of recurrence, with persisting worry and distress sometimes reaching resources in their communities.
levels of clinical anxiety, is common, occurring in up to 80% of cancer
survivors.519 This fear can increase at times of routine cancer surveillance For additional information regarding anxiety, depression, and distress in
testing or with physical symptoms that may or may not be related to the patients with cancer, please see the NCCN Guidelines for Distress
cancer diagnosis.19,69,510-512,520 Anxiety and/or depression can also occur in Management (available at www.NCCN.org). The NCCN Guidelines for
survivors secondary to physical compromise, social isolation, or work and Survivorship complement the NCCN Guidelines for Distress Management.
financial problems that result from cancer treatment.66,69,73,512,521 These These guidelines may be modified to accommodate the individual
challenges are accentuated by the usual decreased medical and circumstances of cancer survivors.
interpersonal support following completion of treatment and transition to
Screening for Anxiety, Depression, and Distress
the surveillance phase of care.179
Psychosocial problems are pervasive in survivors and many distressed
66,69,74-76,522,523 survivors may not appear distressed. Therefore, all survivors should be
Anxiety and/or depression affect up to 29% of survivors.
Studies also show that 17% to 38% of survivors have PTSD symptoms screened for anxiety, depression, and distress, especially at times of
while 5% to 12% meet full criteria, and symptoms do not resolve with time disease transition, surveillance, significant loss, major life events, and
for many survivors.519 A meta-analysis determined the log odds ratio for a social isolation. Survivors who present with multiple or repeated somatic
PTSD diagnosis in cancer survivors compared with non-cancer controls to complaints should also be screened as part of their overall workup.
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The panel lists questions that can be asked of survivors to determine if factors to assess include previous attempts at suicide or self-injury, a
they have been feeling nervous/anxious or sad/depressed and whether family history or other exposure to suicide, not having a spouse or live-in
these moods are impacting quality of life. The panel does not recommend partner, social isolation, and other factors that suggest difficulty with
use of the NCCN Distress Thermometer (DT) as an initial screening tool in severe stress. These include perceiving oneself as a burden, recent loss
survivors, because studies generally find that it lacks sufficient sensitivity of an important person, a relationship breakdown, chronic illness or recent
and specificity in this population.526-533 For example, a study of 120 change in health status, alcohol or other substance abuse, loss of rational
survivors of adult-onset cancer found that the DT had a sensitivity of thinking, feeling hopelessness or loss of control, financial instability, and
47.6% and 51.7%, using cutoff values of 5 and 4, respectively.531 The access to firearms/weapons or potentially lethal medications (eg, opioids,
panel therefore recommends supplemental screening when the DT is used benzodiazepines [BZDs], antidepressants). Males and those in their late
as an initial screening tool. Survivors with an elevated level of distress by teens or age >55 years are also at elevated safety risk. Medical risk
the DT should still be asked the initial screening questions provided in factors should also be assessed, including the presence of a sleep
these guidelines. These more specific questions allow the clinician to disorder, which has been shown to be associated with an increased risk of
determine what particular psychological symptoms are affecting the suicide.536
survivor and may provide more sensitivity and specificity than the DT in
identifying distressed survivors who need treatment or additional Protective factors also should be considered to balance against risk
resources. factors.535 Survivors who are married, have child-rearing responsibilities,
and/or are employed are less likely to pose a danger to themselves or
Diagnosis of Anxiety, Depression, and Distress others. In addition, survivors with strong interpersonal bonds to family or
Oncologists and PCPs generally do not feel comfortable diagnosing major community, who identify reasons for living, or with cultural, spiritual, and
psychiatric disorders, nor should they be doing so. Therefore, these religious beliefs about the meaning and value of life are at lower risk. The
guidelines do not specify the full diagnostic criteria for depression, anxiety, panel lists additional protective factors in the algorithm above.
PTSD, etc. Instead, the guidelines list the essential criteria for screening
psychiatric diagnoses that are most common in survivors and some key Survivors with suicidal or homicidal thoughts or a plan and/or with multiple
symptoms from the Diagnostic and Statistical Manual of Mental Disorders other risk factors are at an elevated risk of danger to themselves or others.
(5th ed.; DSM-5534). The panel’s intent is to provide information to facilitate In addition, the inability of the survivor to care for his- or herself may also
initial steps in providing care and decisions about referrals rather than to indicate an elevated safety risk. Survivors judged to be at elevated risk
provide guidelines for psychiatric diagnosis and extended treatment. require an emergency intervention that includes arranging to have
weapons secured, maintaining direct observation of the individual, and
Safety Evaluation possibly calling 911, along with following other state mental health
Cancer survivors with anxiety, depression, PTSD, or another psychiatric emergency plans or referring the person to emergency psychiatric
disorder that is impacting quality of life should undergo a safety evaluation evaluation procedures onsite.
to assess whether they are a danger to themselves or others.535 Risk
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Survivors with intermittent suicidal ideation or thoughts that they might be emotional, spiritual, intimacy, and practical needs. Additional treatment
better off dead, but no plan to harm themselves nor thoughts of options are described below.
endangering others, are at lower safety risk, as are those with fewer risk
factors. A safety plan should be developed with these survivors and their Nonpharmacologic Treatments
families and should include immediate referral for mental health evaluation Treatment recommendations for managing depression, anxiety, and
based on urgency, regular follow-up and monitoring until psychiatric care distress include a strong recommendation for regular physical activity,
is in place, and having the survivor agree to contact a health care provider, which has been shown in clinical trials and meta-analyses to have
call 911, or go to an emergency room if suicidal thoughts increase or significant effects in reducing symptoms of anxiety and depression among
change. Underlying conditions and risk factors that contribute to suicidal survivors.537-539 In fact, evidence suggests that exercise and
thoughts should be addressed whenever possible. antidepressants (discussed below) may be equally effective in the
treatment of depression.540
Management of Anxiety, Depression, and Distress
Survivors with suspected major psychiatric diagnoses, including mania or Psychotherapy, and in particular cognitive behavioral therapy (CBT) and
psychosis, those with an extensive psychiatric history, and those with a problem-solving therapy, have been shown to be effective at treating
moderate to high safety risk should be referred for psychiatric evaluation depression, anxiety, and PTSD in the general population.541-546 Therapy,
and treatment. Survivors with substance abuse issues should be referred including CBT, has also been shown to be effective at reducing anxiety,
to a substance abuse specialist. Survivors with moderate- to severe- depression, and distress in the survivorship population.179,547-555 One study
intensity major depression, generalized anxiety, panic, or PTSD also found that a psychoeducation program that included three telephone-
should be referred for evaluation and treatment by a mental health based psychotherapy sessions reduced the severity of fear of recurrence
professional; however, pharmacologic and/or nonpharmacologic in melanoma survivors.556 Another study randomly assigned 222
treatments, as described below, can also be considered for these participants to either an attention control or to five face-to-face sessions of
survivors. a program called ConquerFear, which included attention training,
metacognitions, acceptance/mindfulness, screening behavior, and values-
All treatable contributing factors (eg, pain, sleep disturbance, fatigue, based goal setting.557 Those in the ConquerFear group experienced
metabolic/endocrine problems, other medical comorbidities) should be clinically and statistically greater improvements in total scores immediately
addressed. Reassurance can be offered that symptoms of worry, stress, post-therapy and 3 and 6 months later on the Fear of Cancer Recurrence
anxiety, and depression are common problems among cancer survivors Inventory than those in the control group. Greater improvements were also
and that these symptoms can be treated. In addition, support and seen immediately post-therapy in symptoms including total cancer-specific
education should be provided to the survivor and family regarding normal distress and general anxiety.
recovery phases after treatment, common stresses, distress, and fears,
and strategies for managing uncertainty and distress. Finally, resources Other alternative treatments (eg, yoga, tai chi, mindfulness) may also be
need to be provided for social support networks and specific social, helpful to survivors suffering from distress, although data showing their
effectiveness are limited.558-562 Mindfulness is possibly the best-studied
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alternative treatment for psychological problems in cancer survivors.563-567 several different drugs may be needed to find the best option for an
For example, a randomized controlled trial of 322 survivors of breast individual. BZDs (ie, clonazepam, lorazepam) can be used for acute
cancer found that a 6-week mindfulness-based stress reduction (MBSR) anxiety relief or while waiting for antidepressants to take effect. The BZD
program reduced anxiety and fear of recurrence and also improved dose should be adjusted once SSRIs or SNRIs are fully effective and
fatigue.567 In non-cancer settings, weight loss interventions have improved symptoms are partially or completely abated. Survivors should also be
depression in obese individuals,568 although evidence in cancer or survivor counseled that symptoms of withdrawal may occur should any of the
populations is lacking. above-mentioned medications be abruptly discontinued. Referral to a
mental health professional should be considered if the response to first-
Pharmacologic Treatments line treatment is inadequate.
Cancer survivors use medication for anxiety and depression at a rate
about twice that of the general population.569 A population-based study in Cognitive Dysfunction
Canada found that 44% of cancer survivors were using an anxiolytic, and Cognitive impairment is a common complaint among cancer survivors and
22% were using an antidepressant.570 Antidepressants and antianxiety may be a consequence of the tumors themselves or of the direct effects of
drugs have been shown to be beneficial for the treatment of depression cancer-related treatment (eg, chemotherapy, radiation therapy). This
and anxiety in patients with cancer.571-578 Evidence of these effects is symptom may be especially prominent in survivors of primary central
lacking in cancer survivors, although these drugs have been studied in this nervous system (CNS) cancers or those with brain metastases, but
population for their effects on vasomotor symptoms (see Hormone- survivors who never had brain involvement may also report difficulties in
Related Symptoms). Selective serotonin reuptake inhibitors (SSRIs) and cognition.582 For some survivors, symptoms persist long-term.583 When
serotonin-norepinephrine reuptake inhibitors (SNRIs) can therefore be severe, the presence of cognitive dysfunction can impact quality of life and
used in survivors with moderate- to severe-intensity major depression, function. Cognitive dysfunction is most commonly connected with
generalized anxiety, panic, or PTSD. SNRIs should be considered for chemotherapy (sometimes referred to as “chemobrain”), but evidence
concomitant pain or concomitant hot flashes (also see Hormone-Related suggests that therapies other than chemotherapy, such as endocrine
Symptoms). Psychotropics with cytochrome P450 interactions (ie, therapy, radiation, and surgery may be associated with cognitive
fluoxetine, paroxetine, sertraline, bupropion, fluvoxamine, nefazodone, impairments.584-594 A national cross-sectional study found that a history of
duloxetine, clomipramine) should be used with caution in survivors taking cancer is independently associated with a 40% increase in the likelihood
tamoxifen. Pure SSRIs, and in particular paroxetine, block conversion of of self-reported memory problems.595
tamoxifen to active metabolites through CYP2D6 and should be used with
caution for women on tamoxifen (see Hormone-Related Symptoms for a Cancer-related cognitive changes have primarily been studied in patients
discussion of psychotropics and cytochrome P450 interactions).579-581 with CNS cancer, breast cancer, and lymphoma and in those who have
undergone hematopoietic stem cell transplant (HSCT), with a reported
Survivors should be counseled that it may take up to 2 to 6 weeks at a incidence ranging widely from 19% to 78%.583,596-610 In the 2010
therapeutic dose for SSRIs and SNRIs to take effect, and that a trial of LIVESTRONG survey of 3108 post-treatment survivors of a variety of
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cancer types, approximately 46% of respondents perceived cognitive survivors of head and neck cancer (eg, in intellectual capacity,
deficits.611 In a prospective, longitudinal study of 581 patients with breast concentration/short-term attention, verbal memory, executive function) and
cancer treated at several U.S. community oncology clinics and 364 survivors with a history of hematopoietic cell transplantation (HCT) (eg, in
controls, patients reported significantly greater cognitive difficulties than fine motor dexterity, verbal speed, processing speed, auditory memory,
controls before chemotherapy, post-chemotherapy, and after an additional executive function).618,619
6 months, with 45% of patients reporting a decline in cognitive function
over time compared with 10% of controls.612 The correlation between patient reports of cognitive decline and results of
neuropsychological testing has not been consistently demonstrated,
Growing evidence supports the patient experience of cognitive dysfunction possibly because of various definitions of cognitive dysfunction and
associated with cancer diagnoses and treatments, with deficits commonly differences in the statistical analyses across studies.609 Other reasons for
occurring in the domains of executive function, learning and memory, the weak correlation between perceived and objective cognitive decline
attention, and processing speed.583,609,613-615 In one meta-analysis of 17 have been proposed, including the fact that perceived cognitive decline is
studies, women previously treated with chemotherapy for breast cancer (n influenced by patient expectations whereas expectations do not affect
= 807) had lower functional abilities than those not treated with objective assessments and that objective assessments assess cognitive
chemotherapy (n = 291).600 These deficits were limited to verbal (eg, word- performance under optimal rather than real-life conditions.620 However,
finding) and visuospatial (eg, copying complex images) abilities. However, some studies have shown a strong correlation. For example, a study of
when compared with their pre-chemotherapy baseline, no differences 189 breast cancer survivors found that memory and executive function
were noted among patients complaining of cognitive dysfunction. In complaints, present in approximately 20% of the cohort, showed a
another study, cognitive function was compared among 196 long-term statistically significant association with results of domain-specific
survivors of breast cancer treated with cyclophosphamide, methotrexate, neuropsychological tests.621 A study that included 291 participants with
and fluorouracil (CMF) who were, on average, 21 years out from stage I–III colorectal cancer before or after surgery and healthy controls
diagnosis, and 1509 control patients with no history of cancer.616 The found that 45% of patients with cancer had cognitive impairment versus
chemotherapy group did significantly worse on several neuropsychological 15% of the control group (odds ratio [OR], 4.51; P < .001), with the largest
tests (eg, immediate and delayed verbal memory, executive functioning, effects seen in complex processing speed, attention/working memory, and
psychomotor speed). Another study compared 101 patients who verbal learning efficiency.589 Results of this study suggest that the cancer
underwent an HSCT with 82 patients treated with a non-myeloablative diagnosis itself and/or the surgical intervention contribute to cognitive
therapy; both groups showed mild cognitive impairments at baseline.617 dysfunction, because these patients had not received chemotherapy at the
Although no significant differences in cognitive dysfunction were identified time of neurocognitive testing.
at 2-year follow-up, patients who underwent HSCT had poorer
performances in several areas, including executive and psychomotor The underlying mechanisms that might increase the risk for cancer-related
functions and attention. More recent prospective, longitudinal studies have cognitive changes are not known. Studies have reported elevated levels of
seen declines in neurocognitive or neuropsychological test results in cytokines or DNA damage as some of the possible mechanisms.622
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Survivorship
Structural studies have supported the hypothesis that neurotoxicity medications can also contribute to cognitive impairment. Therefore,
resulting in damage to white matter of the brain may play an important role current medications, including over-the-counter medications and
in cognitive deficits after chemotherapy treatment,583,586,599,623,624 and supplements, should be reviewed.
functional MRI studies show that changes in brain activity accompany
cognitive complaints or cognitive deficits in survivors.624-626 In addition, For those who present with concomitant focal neurologic deficits and those
insomnia, fatigue, and depression, common in cancer survivors, may whose symptoms evolve to include these findings, imaging is indicated to
negatively influence cognitive function, although several studies have rule out structural abnormalities (ie, brain or CNS disease). In addition,
found that cognitive dysfunction does not correlate with mood.616,627,628 imaging in the absence of focal findings may be appropriate for patients
Psychosomatic effects can also contribute, as evidenced by a study of deemed to be at high risk for recurrence or metastatic disease involving
patients to be treated with chemotherapy that found that those who were the CNS.
informed of the possible cognitive side effects were more likely to report
Unfortunately, no effective brief screening tool for cancer-associated
cognitive dysfunction and perform worse on neuropsychological testing
cognitive dysfunction in the asymptomatic cancer survivor currently exists.
than uninformed patients.629 A better understanding of the mechanisms
The Mini-Mental State Examination (MMSE634) and similar screening tools
that cause cancer-related cognitive impairment is essential for the
lack adequate sensitivity to detect the subtle decline in cognitive
development of treatments to improve cognitive function and quality of life
performance seen in most cancer survivors. Instead, the panel listed
in patients with cancer and survivors.582,630,631
several questions that can help clarify the nature of the impairment,
In October 2006, the International Cognition and Cancer Task Force including inquiries about the ability to pay attention, find words, remember
(ICCTF) was formed, comprising a multidisciplinary group of health things, think clearly, and perform functions. The time of onset of symptoms
professionals and health advocates. The mission of ICCTF is to advance and the trajectory over time should also be assessed.
understanding of the impact of cancer and cancer-related treatment on
Management of Cognitive Dysfunction
cognitive and behavioral functioning in patients with CNS and non-CNS
Survivors benefit from validation of their symptom experience and should
cancers.632 The group published recommendations regarding
be reassured that, in most survivors, cognitive dysfunction does not
neuropsychological testing, defining cognitive impairment/changes,
worsen over time. In fact, data from breast cancer survivors suggest that
neuroimaging, and future study design.631,633
symptoms may improve over time.585 The panel recommends the use of
These NCCN Guidelines address cognitive function of survivors with non- nonpharmacologic interventions whenever possible, with pharmacologic
CNS malignancies who did not have CNS-directed therapies. interventions as a last line of therapy in survivors for whom other
interventions have been insufficient, as discussed in the following
Assessment and Evaluation for Cognitive Dysfunction sections. Additional recommendations for cognitive dysfunction in older
Patients who report cognitive impairment should be screened for adults can be found in the cognitive function section of the NCCN
potentially reversible factors that may contribute to cognitive impairment, Guidelines for Older Adult Oncology (available at www.NCCN.org).
including depression, pain, fatigue, and sleep disturbance. Some
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Survivorship
Nonpharmacologic Interventions for Cognitive Dysfunction improved processing speed among those who had been diagnosed within
Prospective data to inform the use or potential benefits of non- the past 2 years, but no other significant differences were observed.
pharmacologic interventions for cancer survivors who complain of
Cognitive training (ie, brain games) can also be considered. Cognitive
cognitive dysfunction are limited. Practical suggestions include instruction
training has demonstrated benefits in self-reported and objectively
in self-management and coping strategies (eg, using planners, reminder
assessed cognitive function, including memory, executive function, and
notes, and/or smart phone technology; keeping items in the same place),
verbal function.639,643 One study randomized 157 breast cancer survivors to
which the panel believes can be very helpful to patients. Discontinuation or
limitation of use of medications known to cause or contribute to cognitive web-based cognitive training with telephone support or to wait-list
control.644 Verbal learning and results on a working memory test showed
impairment should be attempted. Management of depression/emotional
statistically significant improvement in the cognitive training group, but no
distress, pain, sleep disturbances, and fatigue should be provided. In fact,
improvements were seen for an objective measure of working memory
a study showed that CBT for fatigue was effective at reducing self-
and a measure of perceived cognitive functioning. Another study used a 5-
reported cognitive disability and concentration problems in 98 severely
session, small-group intervention of psychoeducation and cognitive
fatigued cancer survivors randomized to CBT compared with those
randomized to a wait list.635 However, no difference in neuropsychological exercises in 48 breast cancer survivors.645 Compared to survivors
randomized to a wait-list control group, survivors in the intervention arm
test performance was observed.
experienced improvements in self-reported cognitive complaints and
CBT for cognitive dysfunction may also help some survivors. In one small memory functioning on neurocognitive testing. A larger study of 242
study, CBT was evaluated in 40 breast cancer survivors using a waitlist survivors with self-reported, persistent cognitive symptoms after
control trial design.636 Although overall quality of life improved with the chemotherapy for non-CNS cancers found that survivors randomized to a
intervention, statistically significant improvement was noted only with web-based cognitive training program had statistically significant
verbal memory, not with self-reports of daily cognitive complaints. Another improvements in perceived cognitive impairment immediately and 6
study of CBT delivered by video conference in 47 survivors of breast months after the intervention.646 Improvements in anxiety, depression,
cancer found that CBT led to improvements in self-reported cognitive fatigue, and stress were also seen after the intervention, which used
impairment and in neuropsychological processing speed compared with adaptive exercises that targeted cognitive domains, such as visual
supportive therapy.637 precision, working memory, and visual processing speed.
Routine physical activity should be encouraged. Substantial evidence Relaxation, stress management, meditation, and yoga can also be
shows that physical activity enhances cognitive function in elderly people considered. A small pilot randomized controlled trial of 71 fatigued
in general, although only few studies specific to cancer survivors have survivors showed that MBSR improved some domains of cognitive
been reported.638-642 A small randomized controlled trial of an exercise function.647 A larger study also found improvements in cognitive symptoms
intervention versus control in breast cancer survivors evaluated objective after a mindfulness-based approach.565 Two studies have assessed the
and self-reported cognition.642 The exercise intervention significantly
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effects of yoga on cognition in survivors.648,649 Both reported improvements found that participants receiving modafinil performed significantly better on
in patient-reported cognitive dysfunction. cognitive tests of attention and psychomotor speed.655 Benefits with
treatment were also noted among patients with primary brain tumors.656
Neuropsychological evaluation can be therapeutic and validating.
Evaluation may also be necessary if an individual is pursuing disability Donepezil is an acetylcholinesterase inhibitor used to treat patients with
benefits and cognitive impairment is a contributing factor to work limitation. Alzheimer’s disease. It has been studied for its effects on cognitive
Cognitive rehabilitation, including occupational therapy, speech therapy, impairments after the treatment of brain tumors, with modest
and treatment by a neuropsychologist, may also be useful. Occupational improvements seen in attention/concentration, memory, and motor speed
therapy strategies focus on improvement of cognitive functioning and may and dexterity.657,658 Donepezil was also studied in a randomized trial of 62
be most effective for individuals who note the impact of specific functional breast cancer survivors who had received adjuvant chemotherapy.659
limitations, such as word finding, comprehension, and task completion, on Although there were no differences in subjective cognitive function, the
work performance, quality of life, or role expectations.650 Psychotherapy is donepezil group showed improved memory on objective tests. Further
another option. work is needed before concrete recommendations for pharmacologic
therapy in survivor populations can be made.
Pharmacologic Interventions for Cognitive Dysfunction
If nonpharmacologic interventions have been insufficient, consideration of Fatigue
a trial of medications such as methylphenidate, modafinil, or donepezil is Note: The Discussion text regarding fatigue in survivors has been adapted
reasonable in select survivors or certain clinical scenarios, although data from the NCCN Guidelines for Cancer-Related Fatigue (available at
informing the efficacy of these agents are lacking. Trials assessing the www.NCCN.org).
effects of the psychostimulant methylphenidate have reported mixed
results.651 For example, a randomized, placebo-controlled, double-blind NCCN defines cancer-related fatigue as “a distressing, persistent,
trial found that d-methylphenidate had no effect on neuropsychological test subjective sense of physical, emotional, and/or cognitive tiredness or
scores.652 In contrast, a randomized, double-blind, crossover trial of child exhaustion related to cancer or cancer treatment that is not proportional to
survivors of acute lymphoblastic leukemia (ALL) or brain tumors showed recent activity and interferes with usual functioning.”660 Fatigue is a
that methylphenidate was more effective than placebo at improving common symptom in patients with cancer and is nearly universal in those
attention, cognitive flexibility, and processing speed.653 receiving cytotoxic chemotherapy, radiation therapy, bone marrow
transplantation, or treatment with biological response modifiers.661-663
Results of studies on modafinil, another psychostimulant, are more According to a survey of 1569 patients with cancer, the symptom is
consistent. A randomized controlled trial assessing the efficacy of experienced by 80% of individuals who receive chemotherapy and/or
modafinil for fatigue and cognitive function in breast cancer survivors radiotherapy.664,665 Cancer survivors report that fatigue continues to be a
found significantly greater improvement in memory and attention among disruptive symptom after treatment ends,666-674 with studies showing that
patients receiving modafinil than in the placebo group.654 Similarly, a 17% to 29% of cancer survivors experience persistent fatigue for years
double-blind, randomized, crossover trial also in breast cancer survivors
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after the completion of active therapy.675-677 In fact, a study of 6011 long- require no further assessment or interventions; these patients should be
term cancer survivors found that 39% to 51% (depending on tumor type) rescreened at regular intervals. Patients with scores of 4 or greater or
were classified as fatigued after completion of the Fatigue Assessment indicating moderate or severe fatigue should be evaluated further. Studies
Scale compared with 21% of a representative normal population.678 in patients with cancer have revealed a marked decrease in physical
functioning at a reported fatigue level of 7 or higher on the 0 to 10
Persistent cancer-related fatigue affects quality of life, because individuals scale.690,691
become too tired to fully participate in the roles and activities that make life
meaningful.668,679 In fact, severe fatigue in survivors of Hodgkin lymphoma Evaluation for Moderate to Severe Fatigue
is associated with a decreased likelihood of employment.680 Disability- When fatigue is rated as moderate to severe, with a score of 4 to 10, a
related issues are also relevant for cancer survivors, because obtaining or more focused history and physical examination should be conducted. A
retaining disability benefits from insurers is often difficult for patients with thorough history is warranted, because the recommended workup for
cancer-related fatigue. Identification and management of fatigue remain an fatigue differs according to the timing of fatigue onset in relation to the
unmet need for many cancer survivors. completion of active therapy and the presence of predisposing factors and
other symptoms. Fatigue has a variable natural history, with some patients
The specific mechanisms involved in the pathophysiology of cancer- complaining of only mild levels of fatigue even during active therapy and
related fatigue are unknown. Proposed mechanisms include pro- others experiencing severe fatigue for years after treatment completion.
inflammatory cytokines, hypothalamic-pituitary-adrenal (HPA) axis
dysregulation, circadian rhythm desynchronization, skeletal muscle In general, mild to moderate levels of fatigue that persist for 6 to 12
wasting, and genetic dysregulation.681-686 Several studies have focused on months after the completion of therapy do not warrant an extensive
the cause of fatigue, especially in cancer survivors with no evidence of workup, unless other symptoms are present. Conversely, when moderate
active disease, and have suggested that persistent immune system to severe fatigue begins after or worsens during this period, or when other
activation and chronic inflammatory processes may be involved.666,687-689 symptoms are present, such as pain, pulmonary complaints, or
Evidence supporting these mechanisms is limited. unintentional weight loss, a more extensive workup is warranted to screen
for the presence of metastatic disease or other comorbidities. Referral to a
Screening for Fatigue pulmonologist should be made for pulmonary complaints.
All survivors should be screened for fatigue to ensure that those with
moderate to severe fatigue are identified and treated promptly and Regardless of fatigue onset, it is always relevant to screen for common
effectively. Because fatigue is a subjective experience, clinicians must rely contributing factors such as emotional distress, sleep disturbance, pain,
on patients’ descriptions of their fatigue level. The panel recommends the and the use of prescriptions or over-the-counter medications or
use of a severity scale, with survivors being asked, “How would you rate supplements. Possible medical causes of fatigue, including cardiac
your fatigue on a scale of 0 to 10 over the past 7 days?” Alternatively, disease, gastrointestinal or hepatic dysfunction, and hypothyroidism,
screening can be performed with patients asked to rate their fatigue as should also be assessed. Disease and treatment considerations also
none, mild, moderate, or severe. Scores of 0 to 3 or none to mild fatigue affect recommendations for screening, such as the inclusion of
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echocardiograms for patients who received cardiotoxic treatments and Physical Activity
thyroid screening for patients who received radiation to the neck or thorax Activity enhancement is a category 1 recommendation for the
or agents such as immunotherapies or small molecule TKIs. management of fatigue in survivors. Improving strength, energy, and
fitness through regular exercise, even a moderate-intensity walking
Management of Fatigue
program, has been shown to facilitate the transition from patient to
Several interventions and strategies have been shown to help alleviate
survivor, decrease anxiety and depression, improve body image, and
fatigue and reduce distress caused by this symptom in patients with
increase tolerance for physical activity. Therefore, survivors with moderate
cancer and survivors; recommended strategies and interventions are
to severe fatigue should be encouraged to maintain adequate levels of
described herein. For additional information about fatigue in survivors and
physical activity (category 1). Robust data support the efficacy of
patients with cancer, please see the NCCN Guidelines for Cancer-Related
increased physical activity for reducing fatigue in patients with cancer and
Fatigue (available at www.NCCN.org). These guidelines may be modified
survivors.204,210,215,217,219,560,694-700 Multiple meta-analyses of randomized
to fit the individual survivor’s circumstances.
controlled trials have found that cancer survivors who participate in
exercise interventions, either during or after treatment for cancer,
Treatment of Contributing Factors
experience significant improvements in fatigue compared with patients
Management of fatigue in survivors first includes the treatment of
randomized to the control group.204,700-703 A randomized phase 3 trial that
contributing factors such as pain, distress, anemia, and sleep disturbances
included 410 cancer survivors showed that a 4-week yoga therapy
(more information on the treatment of pain, anxiety/depression, and sleep
program led to improvements in fatigue and sleep quality and reductions in
disorders in survivors can be found throughout these guidelines). In a
daytime dysfunction.704
randomized controlled trial of 152 fatigued patients with advanced cancer,
treatment of accompanying physical symptoms, including pain, nausea, Survivors at a higher risk of injury should be referred to a physical
vomiting, and shortness of breath, resulted in a significantly higher impact therapist or exercise specialist (also see Healthy Lifestyles, above).
on general fatigue, activity, and motivation than usual care.692
Psychosocial and Other Interventions
Patient and Family Education and Counseling Psychosocial interventions, such as CBT, MBSR, psycho-educational
Education and counseling can be beneficial in helping patients cope with therapy, and supportive expressive therapy, including support groups,
fatigue. Understanding typical patterns of fatigue during and after counseling, and journal writing (all category 1 recommendations), have
treatment can help patients set reasonable expectations regarding also been shown to reduce fatigue in cancer survivors, although data are
improvements in energy after the completion of cancer therapy and can not entirely consistent.567,705-710 Several meta-analyses have evaluated the
help allay concerns that persistent fatigue after the completion of therapy role of psychosocial interventions in reducing fatigue.700,705,709,711 For
is evidence of disease recurrence. Counseling can help patients develop example, Kangas et al709 reported a weighted pooled mean effect of −0.31
strategies for self-monitoring of fatigue and techniques such as energy for psychosocial interventions on fatigue in an analysis of 3620 patients
conservation that may be helpful in the immediate post-treatment period.693 with cancer from 41 studies. Jacobsen et al711 analyzed 30 randomized
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controlled trials and found a significant effect size (dw) for psychological acceptable option that may improve symptoms for survivors with moderate
interventions (dw, 0.10; 95% CI, 0.02–0.18) but not for activity-based to severe fatigue.
programs (dw, 0.05; 95% CI, −0.08–0.19). A meta-analysis by Duijts et
al705 reported that, like exercise programs, behavioral techniques, including Pharmacologic Interventions
CBT, relaxation techniques, counseling, social support, hypnosis, and Psychostimulants, such as methylphenidate, are also used to treat fatigue,
biofeedback, are beneficial in improving fatigue among patients with although data regarding their use to treat fatigue in cancer survivors are
breast cancer during and after treatment (standardized mean difference very limited. A 54% response rate to methylphenidate was reported in a
[SMD], −0.16). phase II trial of 37 breast cancer survivors.728 A randomized trial in 154
patients post-chemotherapy also found an improvement in fatigue
Several published studies support the conclusion that CBT interventions symptoms in the dexmethylphenidate arm.729 A recent meta-analysis of
designed to optimize sleep quality (CBT for insomnia; CBT-I) in patients five randomized controlled trials of patients with cancer found limited
with cancer may also improve fatigue.712-716 Two randomized clinical trials evidence for the efficacy of 4 or more weeks of methylphenidate treatment
of patients who reported chronic insomnia in the survivorship phase for cancer-related fatigue (mean difference, −3.70; 95% CI, −7.03 to
demonstrated improvements in both sleep and fatigue after 4 to 5 weekly −0.37; P = .03).730 However, another meta-analysis identified seven trials
behavioral therapy sessions.706,707,717 Two smaller studies of patients with of methylphenidate and concluded that it was superior to placebo for the
current complaints of insomnia in the survivorship phase reported treatment of cancer-related fatigue.731 A Cochrane review found that
improved sleep and fatigue.712,715 Two other studies found positive benefits methylphenidate was likely effective for cancer-related fatigue and
of a behavioral intervention on sleep and fatigue that were not sustained warrants further study.732 However, a second comprehensive meta-
over time.716,718 The American Academy of Sleep Medicine (AASM) has analysis did not support this finding, nor did it support the use of
recommended three specific therapies for the initial approach to chronic pharmacologic interventions for the treatment of cancer-related fatigue.700
insomnia in healthy individuals: relaxation therapy, CBT-I, and stimulus
control therapy.719 Other drugs, including modafinil, have also been studied for post-
treatment fatigue.733,734 In particular, a large phase III trial of 631 patients
Acupuncture and acupressure have been studied for the treatment of receiving chemotherapy suggested that modafinil is beneficial in patients
fatigue in patients with cancer and survivors.720-727 A pilot study in 30 breast with severe fatigue.734 However, a placebo-controlled, double-blind,
cancer survivors found that acupuncture resulted in a significant reduction randomized controlled trial in 208 patients with non-small cell lung cancer
in fatigue after 2 weeks.725 In addition, a phase 3 randomized, single-blind (NSCLC) showed no effect of modafinil on cancer-related fatigue.735 In
clinical trial in 424 breast cancer survivors found that self-administered addition, a meta-analysis identified three studies evaluating modafinil for
relaxing acupressure reduced persistent fatigue and improved sleep fatigue in patients with cancer and found that the drug was not better than
quality and quality of life.727 Although results of studies are mixed and placebo.731 Recommendations for modafinil have therefore been removed
many compared acupuncture to usual care rather than sham acupuncture from both the NCCN Guidelines for Cancer-Related Fatigue and the
or another active comparator, the panel believes acupuncture is an NCCN Guidelines for Survivorship. Both guidelines continue to
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recommend that methylphenidate may be considered after ruling out other half reported moderate to extreme distress related to their lymphedema.742
causes of fatigue and failure of other interventions, although they Lymphedema can also affect social roles, employment, medical expenses,
acknowledge the limited data supporting the use of this agent in this physical function, and quality of life and can cause disability.743-746
setting, especially in cancer survivors. Unfortunately, only 55% of cancer survivors with self-reported
lymphedema in the LIVESTRONG study said that they received care for
Small pilot studies and one recent randomized controlled trial have lymphedema.23
evaluated the impact of supplements, including ginseng and vitamin D, for
cancer-related fatigue.736 The evidence to date is inconsistent, and the Risk Factors for Lymphedema
panel currently does not recommend the use of supplements for the Survivors whose cancer treatment included surgery and/or radiation to the
treatment of fatigue. axillary, supraclavicular, cervical, or inguinal lymph node system are at risk
for the development of lymphedema.747-750 Sentinel lymph node biopsy also
Lymphedema appears to increase the risk of lymphedema, although it poses less risk
Lymphedema is a common side effect of cancer treatment, occurring on than complete dissection or radiation to the nodal group, and data are not
the same side of the body as the cancer treatment, resulting from damage completely consistent.748,751-755 Other treatment-related factors that have
to the lymphatic system. It occurs when lymph fluid accumulates in the been associated with an increased risk of lymphedema are receipt of
interstitial tissue, causing swelling of the limb or other areas such as the chemotherapy or radiation and the extent of lymph node
neck, trunk, or genitals. Lymphedema is most often diagnosed within 18 dissection.737,738,747-750,753,755-757 Overweight (BMI ≥25 kg/m2) and obesity
months of treatment; however, it can develop any time in the life of the (BMI ≥30 kg/m2), localized infection, and higher initial stage of disease
survivor. also raise the risk of lymphedema development.737,738,747,748,750,755,757-759
More than 20% of cancer survivors reported lymphedema as a physical Assessment and Workup for Lymphedema
concern in a survey of almost 14 million survivors in the United States in a Survivors with a history of radiation or surgery to the lymph nodes should
2010 LIVESTRONG study.23 The incidence of lymphedema varies by be asked about swelling or feelings of heaviness, fatigue, or fullness at
disease site. In one study, 41% of almost 1000 breast cancer survivors each visit. Early detection and diagnosis are key for optimal lymphedema
developed lymphedema by 10-year follow-up.737 In a study of survivors of management, because stages 0 and 1 are reversible, whereas stages 2
gynecologic cancers, the incidence of lymphedema in one or both legs 2 and 3 are less responsive to treatment (see Definition and Stages of
years after surgery was 37%.738 In one study of 431 survivors of melanoma Lymphedema in the algorithm). Swelling on the same side as the cancer
who had been treated with complete lymph node dissection and/or wide treatment is a universal symptom of lymphedema. Additional initial
local excision and axillary or inguinal sentinel lymph node surgery, the symptoms may include pain or discomfort and/or sensations of heaviness,
reported incidence of lymphedema was 25%.739 fatigue, fullness, and/or tightness in the skin. Symptoms including
decreased range of motion or strength and thickening of the skin may
Lymphedema may cause or exacerbate psychological distress.740,741 In a occur in later stages. If symptoms are present, survivors should be asked
study that included 692 breast cancer survivors with lymphedema, almost
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about the frequency and severity of swelling, pain and/or discomfort, any training. If a certified lymphedema therapist is not available, referral to an
issues with strength or range of motion and mobility (ie, bending, appropriate alternative provider for treatment should be considered.
stretching, flexibility), and whether symptoms interfere with daily activities.
Compression garments have been shown to reduce limb volume, and are
If lymphedema symptoms are present, a recurrence of cancer should be often used with other modalities such as manual lymphatic drainage.762-764
ruled out. The survivor should then be referred to a certified lymphedema Manual lymphatic drainage is performed by a specific massage technique
therapist, if available, for additional assessments. These assessments can designed to encourage lymph fluid to drain from the affected area.
include subjective signs and symptoms of lymphedema and limb volume Systematic reviews and meta-analyses have assessed the efficacy of
measurements. Ideally, pretreatment limb measurement of both sides manual lymphatic drainage in breast cancer survivors with lymphedema
should be performed as a baseline prior to initiation of any therapy for and found that it can provide additional benefit when added to standard
those with treatment-related or individual risk factors. If not, the therapy.765,766 In particular, compression bandaging alone leads to limb
contralateral limb can be used for comparison in the post-treatment volume reductions of 30% to 39%, and manual lymphatic drainage
setting. Clinical examination by a lymphedema therapist may include appears to increase that reduction by an additional 7%.
range of motion, muscle performance, circulation, sensation,
hemodynamic monitoring, and functional mobility. Progressive strength training and physical activity are not associated with
exacerbation or development of lymphedema, and may improve
Survivors with lymphedema should also be assessed for distress (see lymphedema symptoms.214,255-259,767-770 The WISER Survivor trial
Anxiety, Depression, Trauma, and Distress, above). randomized 351 overweight breast cancer survivors with lymphedema to a
control group that received hospital-based care, a home-based exercise
Treatment of Lymphedema
intervention group, a home-based weight loss intervention group, or a
High-level evidence supporting treatments for lymphedema are lacking, combined home-based exercise/weight loss group.771 Although the groups
and most studies have been performed in breast cancer survivors.31,760-762 that included a weight-loss intervention experienced about a 7% to 8%
Most of the recommendations made by the panel are thus based on lower- weight loss, no group experienced improvements in breast cancer-related
level evidence, clinical experience, and expert consensus. lymphedema outcomes. This result suggests that home-based
interventions may not be effective for treatment of lymphedema in cancer
The oncology team should provide education regarding self-care
survivors.
management, including infection prevention measures, risk-reduction
strategies, and maintenance of skin integrity on the affected side (see Progressive strength under supervision is recommended for survivors with
Survivor Lymphedema Education, below). Distress should be treated if lymphedema. However, caution is advised in this population,260 and
present (see Anxiety, Depression, Trauma, and Distress, above). Referral survivors with or at risk for lymphedema should consider discussing
should be made to a certified lymphedema therapist, if available, for physical activity plans with a lymphedema specialist before starting a
prescription and fitting of compression garments, performance of manual program that involves strength training. Survivors with lymphedema should
lymphatic drainage, and direction of supervised progressive strength work with trained exercise professionals with knowledge of cancer-related
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physical activity principles and initiate strength training exercise involving allergens, insect bites, and pet scratches.772,773 The use of moisturizing
the affected body part only if lymphedema is stable (eg, no need for soaps and over-the-counter, fragrance-free emollients may also be
lymphedema therapy within the past 3 months, no recent limb infections helpful.773
requiring antibiotics, no change in limb circumference >10%, no change in
the ability to perform activities of daily living). Survivors should undergo Observational studies have demonstrated that air travel, venipuncture, and
baseline and periodic evaluation for development or exacerbation of blood pressure measurement (via arm cuff) are not associated with
lymphedema and should stop exercise and see a lymphedema specialist if exacerbation or development of lymphedema, and precautionary
exacerbation of lymphedema occurs. Weights should be slowly measures are likely unnecessary.747,749,758,759,774-777 For instance, in one
progressed as tolerated, and lymphedema should be evaluated study of 632 women with breast cancer prospectively screened for
periodically. Compression garments may be required during training lymphedema with 3041 arm volume measurements, no association was
sessions. found between the development of lymphedema and blood draws,
injections, or air travel.759 In the absence of high-level data, however, the
The National Lymphedema Network has published a position statement panel recommends that medical procedures such as venipuncture and
with additional guidance for exercise in individuals with lymphedema.768 blood pressure measurements be done on the non–at-risk arm/limb if
possible.778 If necessary, procedures may be done using the at-risk
Survivor Lymphedema Education
arm/limb. More research is needed to determine the effect of these
Early detection and diagnosis is key for optimal lymphedema management procedures on the risk of lymphedema.
because earlier stages are reversible. Therefore, survivors should be
educated about the signs and symptoms of lymphedema and the Survivors should be informed that lymphedema is not a contraindication
importance of rapid reporting to the treatment team. Survivors should be for physical activity and that no special precautions are required for
told to inform their medical provider if subtle swelling or any other cardiovascular/aerobic exercise or strength training of unaffected limbs.255-
symptoms (eg, fullness, tightness, heaviness, pain) on the treated side are 260
In addition, continued full use of the involved extremity and range-of-
noted. motion exercises should be encouraged to maintain strength and range of
motion even in the presence of lymphedema. Progressive strength training
Survivors at risk for lymphedema and those with lymphedema are at a under supervision is recommended for patients with lymphedema, as
higher risk of localized infection in the affected area. These infections can discussed above (see Treatment of Lymphedema). Exercise and physical
require hospitalization for IV antibiotics. Therefore, survivors with or at risk therapy may also help prevent lymphedema symptoms. In the randomized
for lymphedema should be educated to inform their medical provider controlled Lymphedema Education and Prevention study (CALGB 70305),
immediately of signs of infection in the affected area. Risk of infections can women randomized to the education plus exercise arm self-reported
be reduced by safe pet care and gardening techniques (See greater range of motion at 12 months after lymph node dissection (a pre-
Immunizations and Prevention of Infections, above). Survivors should also specified secondary outcome) compared with women in the education only
be educated on how to maintain skin integrity with meticulous skin care of arm (left, 91% vs. 84%; P = .16; right, 90% vs. 83%; P = .02).779 Finally,
the affected area that includes avoidance of cuts, burns, skin irritants and
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survivors can be informed that water exercise under supervision may be experience menopausal symptoms without meeting the definition of
an option to consider in the absence of any skin integrity and/or incision menopause, including female survivors on tamoxifen or aromatase
issues.780 In a controlled clinical intervention study, 88 patients with inhibitors or with a history of oophorectomy or chemotherapy and male
lymphedema secondary to cancer participated in either a water-based or survivors who received or are receiving androgen ablative therapies (ie,
land-based exercise program.780 A higher proportion of those who ADT). These symptoms can include hot flashes/night sweats, vaginal
performed water exercises experienced a reduction in their secondary arm dryness, urinary complaints, sexual dysfunction, sleep disturbance, mood
limb volume (P = .029) and self-reported frequency of swelling (P = .031). disturbance, depression, cognitive dysfunction, arthralgias/myalgias, and
fatigue. Hormonal symptoms can occur in both men and women. Males
Surveillance of Survivors with Lymphedema
may experience many of the same symptoms as women, as well as
Survivors with lymphedema should have follow-up with the treatment team gynecomastia, decreased testicle size, and thinning of body hair.
as clinically indicated. Clinicians should check range of motion, inquire Hormonal symptoms can have a profound impact on quality of life.783,793
about the fit and age of compression garments, replace compression
garments if needed, and inquire about the performance of prescribed Premenopausal cancer survivors who have received chemotherapy may
exercises and self-care management. Assessment for distress should also experience transient or permanent menopause, dependent on the age of
be performed as part of routine surveillance. the patient and the type of chemotherapy.794-796 If appropriate and desired,
referral for fertility preservation should be considered before
Hormone-Related Symptoms chemotherapy, because studies report that 33% to 73% of premenopausal
Hormonal symptoms in cancer survivors have been most extensively women treated for breast cancer become peri- or postmenopausal after
studied in female survivors after treatment of breast cancer. Hot flashes treatment.783 Younger survivors with irregular menses may have primary
are reported to occur in about 46% to 73% of breast cancer survivors.781-784 ovarian insufficiency and may develop menopausal symptoms.797 These
In one study of breast cancer survivors diagnosed at age 40 years or women may or may not be fertile, and should be counseled about the
younger, 46% of women reported hot flashes, 51% reported vaginal possibility of pregnancy despite amenorrhea if they are sexually active and
dryness, and 39% reported dyspareunia.784 Similarly, about 50% to 80% of do not meet the definition of menopause. In non-cancer populations,
men on ADT experience hot flashes, which can persist after treatment.785- primary ovarian insufficiency or early menopause may be associated with
790
The incidence of gynecomastia in men on ADT varies with the method specific menopause-related health risks. However, there are limited data
of ADT used and can be as high as 80% in men on estrogen therapy.787,791 in cancer survivors.
The NCCN Guidelines for Survivorship define menopause as no menses Assessment and Evaluation for Hormonal Symptoms
for one year in the absence of prior chemotherapy or tamoxifen use or no Survivors with hormonal symptoms disruptive to quality of life should be
menses after surgical removal of all ovarian tissue. Healthy women reach assessed and treated for medical causes of hormonal symptoms such as
menopause at a mean age of 51 years, with 95% of women reaching thyroid disease and diabetes. Lab evaluation includes estradiol, follicle-
menopause between 45 and 55 years of age.792 Many cancer survivors stimulating hormone (FSH), luteinizing hormone (LH), and prolactin, as
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clinically indicated. For peri- or pre-menopausal female survivors who healthy postmenopausal women showed that low-dose paroxetine
have become amenorrheic and later develop bleeding, serial estradiol reduces the frequency and severity of hot flashes.807 Small studies have
levels can be useful to determine return of ovarian function. Other markers shown that SSRIs and SNRIs also reduce the severity and frequency of
including FSH, anti-Müllerian hormone (AMH), and inhibin may provide hot flashes in female cancer and survivor populations.808-817 One of these
additional information on ovarian status in female cancer survivors with studies was a randomized, double-blind, placebo-controlled study in 80
prior chemotherapy or pelvic radiation exposure or those on tamoxifen, but survivors of gynecologic cancers.809 Results showed that 7.5 mg daily of
alone are not reliable to ensure menopausal status.798,799 In male survivors, paroxetine reduced the frequency and severity of vasomotor symptoms
morning total testosterone and free testosterone may also be checked if and the number of resultant nighttime awakenings. However, pure SSRIs,
hypogonadism is suspected.800 For women with complaints of vaginal and in particular paroxetine, should be used with caution in women on
dryness, a pelvic evaluation should be done to assess for vaginal atrophy tamoxifen, because these drugs block the conversion of tamoxifen to
and can be accomplished by referral to an appropriate specialist. active metabolites through inhibition of cytochrome P450 2D6
(CYP2D6).580,818 However, an analysis of a large database that included
Management of Hormonal Symptoms in Female Survivors
almost 17,000 breast cancer survivors found no evidence of an increase in
Management of sexual dysfunction, lack of sexual desire, sleep cancer recurrence in women on concurrent tamoxifen and
disturbance, mood disturbance, depression, cognitive dysfunction, fatigue, antidepressants, including SSRIs such as paroxetine.579 In contrast, a
and arthralgias/myalgias is described in other sections of these guidelines. study of 2430 breast cancer survivors found an increased risk of cancer
Management of hot flashes, vaginal dryness, and urogenital complaints death in those taking tamoxifen and an SSRI.819 The panel recommends
associated with menopause are described herein. The panel prefers the alternative therapy if available for survivors on tamoxifen, although no
use of non-hormonal options as first-line therapy for female survivors with definitive conclusion regarding the impact of the interaction between pure
hormonal symptoms disruptive to quality of life, but hormonal therapies SSRIs and tamoxifen can be drawn. Doses of antidepressants required for
can also be used after consideration of the risks and benefits to an improvements in vasomotor symptoms are typically much lower than those
individual survivor. needed for depression, and the response is typically faster. Side effects
include dry mouth, decreased appetite, fatigue, nausea, constipation, and
Non-Hormonal Pharmacologic Treatment of Hot Flashes
possible sexual dysfunction. Upon discontinuation, SNRIs and SSRIs
For the management of hot flashes, non-hormonal pharmacologic options
should be gradually tapered to minimize withdrawal symptoms.
include antidepressants, anti-convulsants, neuropathic pain relievers, and
Venlafaxine has been the most well studied, and the panel lists
certain anti-hypertensives.801-804 When antidepressants are used, a lower
venlafaxine as the preferred antidepressant for the treatment of vasomotor
dose than typically given for depression is often effective to treat hot
symptoms.
flashes.
The anticonvulsants gabapentin and pregabalin have also been shown to
SSRIs and SNRIs have been shown to improve vasomotor symptoms in
improve hormone-related vasomotor symptoms in the general population
the general population, although the degree of symptom reduction may be
and in female cancer survivors.820-825 For example, one trial of 420
smaller than with hormonal treatments.805-807 A randomized clinical trial in
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survivors of breast cancer experiencing ≥2 hot flashes/day found that 900 menopausal population and in survivors.802,838-845 Vitamin E has been
mg/day gabapentin decreased the hot flash severity score by 46% at 8 thought to have marginal improvement in vasomotor symptoms in both
weeks compared with a 15% reduction in the placebo group.824 The panel general menopause and in patients with breast cancer, but data are
lists gabapentin as the preferred anticonvulsant for the treatment of limited and have shown mixed results.846 Limited data show a possible
vasomotor symptoms. As with antidepressants, the doses of benefit of black cohosh for vasomotor symptoms in the general
anticonvulsants used in this setting are lower than in other settings. Side population.847-849 However, randomized data in breast cancer survivors
effects of anticonvulsants include somnolence, so they may be particularly show no benefit.850 Furthermore, there is concern about potential liver
useful when given at bedtime in patients with hot flashes disturbing sleep. toxicity with long-term use of black cohosh. The panel consensus is that
the efficacy and safety data for these treatments are too limited to make a
Small studies provide evidence that the alpha agonist antihypertensive recommendation for use.
clonidine can reduce hot flashes in some healthy postmenopausal
women.826,827 Randomized controlled trials in breast cancer survivors also Acupuncture is used as a treatment for hot flashes in the general
show that clonidine can reduce hot flash frequency and severity in population, although evidence supporting its benefit is limited in the non-
postmenopausal women taking tamoxifen.828,829 Side effects include sleep cancer setting.851,852 Several studies in women with cancer or female
difficulties, dry mouth, fatigue, dizziness, and nausea. survivors have shown acupuncture to be a safe and effective option for
managing vasomotor symptoms.853-856 In fact, three of these studies
Several studies have compared non-hormonal pharmacologic treatments. compared acupuncture with either venlafaxine or gabapentin and found
For example, venlafaxine has been compared with clonidine in breast acupuncture to be equivalent to or better than drug treatment.853,855,856
cancer survivors.830-832 Results of these studies have varied, but it appears
that venlafaxine may have a faster effect but is less well tolerated than Yoga may also help survivors manage hot flashes. A randomized trial in
clonidine. A randomized, crossover study compared venlafaxine with 355 healthy peri- and postmenopausal women found that yoga improved
gabapentin in breast cancer survivors.825 Whereas both treatments quality of life associated with menopause, including an improvement in the
resulted in similar reductions in hot flash severity, 68% of participants vasomotor symptom domain.857 Another randomized controlled trial
indicated a preference for venlafaxine compared with 32% who preferred showed that yoga improved sleep but did not affect the frequency of
gabapentin. symptomatic burden of vasomotor symptoms.858
Non-Pharmacologic Treatment of Hot Flashes Evidence that exercise/physical activity helps manage hot flashes in
Non-pharmacologic treatments, including acupuncture, exercise/physical postmenopausal women is inconclusive.801,857,859-865 In fact, a randomized
activity, yoga, lifestyle modifications, weight loss if overweight or obese, controlled trial of 261 peri-menopausal and postmenopausal women found
hypnosis, and CBT may help survivors manage hot flashes.309,801,803,804,833-837 no difference in the frequency of hot flashes between those randomized to
Phytoestrogens, botanicals, and dietary supplements are often used for an exercise intervention and the control group.860 A similar trial involving
treatment of vasomotor symptoms; however, data are limited on the 248 women also found that physical activity did not improve vasomotor
effectiveness and safety of these particular treatments in the general symptoms.863 Studies in the survivorship and cancer populations are
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limited and also do not support a role for the use of physical activity control.873 Both of the CBT groups reported a significant decrease in the
specifically to improve hot flash symptoms.866 Despite the lack of data perceived impact of hot flashes compared to the control group.
suggesting a benefit for vasomotor symptoms, the panel believes that Improvements were also seen in sleep quality and the overall levels of
physical activity should be recommended in menopausal cancer survivors menopausal symptoms.
given the many beneficial effects on overall health.
Hormonal Treatment of Hot Flashes
Other lifestyle modifications may also help minimize vasomotor symptoms. MHT is the most effective treatment for the management of vasomotor
In the WHI Dietary Modification trial of 17,473 postmenopausal women symptoms in postmenopausal women.792,874-879 However, the use of long-
who were not taking menopausal hormone therapy (MHT), those who lost term MHT is controversial because, for many women, the health risks
≥10% of their body weight were more likely to eliminate hot flash associated with MHT are thought to outweigh the potential benefits. In the
symptoms than those who maintained their body weight.835 Data in breast past, MHT was typically given to postmenopausal women not only to treat
cancer survivors also suggest that weight loss may help alleviate hot vasomotor symptoms, but with the thought that MHT was effective at
flashes in this population.309,837 A longitudinal study in 761 women showed preventing heart disease. The best data looking at health benefits and
that those who quit smoking saw improvements in the frequency and risks came from the large WHI study that showed that estrogen alone in
severity of hot flashes compared to women who continued to smoke.867 older postmenopausal women with prior hysterectomy was associated
Although studies of this sort have not been done in survivor populations, with an increased risk of stroke and decreased risk of hip fracture, and had
data suggest that survivors who are current smokers are more likely to no effect on coronary heart disease or breast cancer incidence.880 In the
experience hot flashes.868 Individual vasomotor responses to alcohol WHI, estrogen plus progestin in older postmenopausal women with a
vary.869 If alcohol triggers hot flashes in an individual survivor, limiting uterus was associated with a decreased risk of colorectal cancer and hip
intake should be recommended. fracture, and an increased risk of stroke, pulmonary embolism, and
invasive breast cancer.881 The women in these trials also had a higher rate
Evidence suggests that CBT may reduce vasomotor symptoms in the
of death from lung cancer during the intervention and were diagnosed with
general population.870,871 CBT has also been studied for the management
more advanced stages of colorectal cancer during the intervention and
of vasomotor symptoms in cancer and survivor populations. In one trial, follow-up than women who received placebo.882-884 MHT was also
patients with breast cancer were randomized to receive CBT, CBT plus an
associated with an increase in breast cancer incidence and the cancers
exercise intervention, or to a control group.866 Results suggested that CBT
were more likely to be lymph node positive.885,886 However, the absolute
lessened the perceived burden of hot flashes. Another study randomized
numbers of trial participants diagnosed with breast cancer were small, and
96 women with hormonal symptoms after breast cancer treatment to a
the absolute risk was low. After longer follow-up, all-cause, cardiovascular,
group CBT intervention or a usual care group.872 The hot flashes and night and cancer-specific mortality were not affected by MHT.887 A systematic
sweats problem rating was significantly reduced in the CBT arm. Another review of randomized double-blind studies of MHT versus placebo found
trial randomized 254 breast cancer survivors to three groups: therapist- no evidence that MHT affects the incidence of colorectal cancer, but found
guided CBT, self-managed internet-based CBT (iCBT), or wait-list
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that MHT increases the risk of breast cancer and death from lung cancer thromboembolism (VTE) and stroke.896 Micronized progestin may be
in postmenopausal women taking estrogen and progestins combined.888 preferred over medroxyprogesterone acetate (MPA) due to lower rates of
VTE and breast cancer risk. Other hormonal options for treating hot
Data from retrospective studies and an incomplete randomized controlled flashes include novel therapies that combine a selective estrogen receptor
trial suggest that MHT is safe to use in survivors of early-stage modulator (SERM) with estrogen, creating a tissue-selective estrogen
endometrial cancer.889-893 In survivors of breast cancer, the data are complex (TSEC). One of these TSECs contains a conjugated estrogen
inconclusive, because the only two randomized controlled trials of MHT in and the SERM bazedoxifene,897 and is FDA-approved for treating
breast cancer survivors had conflicting results. The HABITS trial found an menopausal symptoms in healthy postmenopausal women. Custom
increased risk of breast cancer recurrence with the use of MHT; the compounded bioidentical hormones are not recommended, because data
cumulative incidence at 5 years was 22.2% in the MHT arm and 8.0% in supporting claims that they are safer and more effective than standard
the control arm.894 In the Stockholm trial, no difference was seen in breast hormones are lacking and they may be harmful.898,899 Furthermore, these
cancer recurrence after 10.8 years of follow-up.895 compounds are contraindicated in survivors of hormonally mediated
cancers, and should only be used with caution in those with increased
Overall, based on these data, the panel believes that MHT can be used in
genetic cancer risk. Young cancer survivors experiencing menopause at
appropriate female cancer survivors. Alternatives to MHT should typically
an early age can consider oral contraceptives or MHT for symptom relief
be tried first and patients should be referred to an appropriate specialist for
and potential cardiac and bone benefits as long as not contraindicated.
dosing and management of MHT. MHT is contraindicated in survivors with
a history of hormonally mediated cancers, although as noted above MHT Treatment of Vaginal Dryness
is likely safe in survivors of early-stage endometrial cancer. Other
Vaginal dryness can be treated with over-the-counter vaginal moisturizers,
contraindications for survivors mirror those for the general population, and gels, oils, and topicals for comfort (category 2B).900,901 Lubricants can be
include a history of abnormal vaginal bleeding, active or recent history of a used for sexual activity.902,903 In one study of breast cancer survivors, the
thromboembolic event, pregnancy, and active liver disease. In addition,
control group used a non-hormonal moisturizer and saw a transient
MHT should be used with caution in survivors with coronary heart disease
improvement in vaginal symptoms.900 Survivors should be cautioned that
or hypertension, in current smokers, and in those with increased genetic
some lubricants may be irritating to the area of application.
cancer risk. In general, the lowest dose possible to control symptoms
should be used, and treatment should be individualized based on risks. Local hormonal treatments can also be used (category 2B), although
some data suggest that they may not be more effective than vaginal gels
Hormonal treatments for the relief of hot flashes in women include
or moisturizers.881,904-910 Furthermore, some controversy exists regarding
combination estrogen and progestins (for survivors with an intact uterus)
their safety in survivors of hormone-dependent cancers.911 However,
or estrogen alone (for survivors without a uterus). There are different local
evidence suggests that local estrogen does not increase the risk of breast
and systemic formulations of hormones including oral, transdermal,
cancer recurrence.912 Vaginal estrogen preparations include rings,
vaginal ring, and an intrauterine device. Estrogen transdermal formulations
suppositories, and creams and have been shown to be effective for
may be preferred over other formulations due to lower rates of venous
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managing symptoms of vaginal dryness in menopausal women.910,913 treatments have not been established. The panel believes that larger trials
Limited data in breast cancer survivors suggest minimal systemic are needed before this technique can be recommended.
absorption with rings and suppositories, and they are therefore preferred
for survivors with hormonally sensitive tumors if estrogen-based treatment Treatment of Urogenital Complaints
is warranted.911,914 Other topical hormones (ie, testosterone, DHEA) can Women sometimes present with urogenital complaints associated with
also be considered, but data regarding their safety or effectiveness are menopause, such as urogenital atrophy and urinary incontinence. The
limited. One randomized controlled trial of 464 survivors of breast or panel recommends treatment with local vaginal estrogen and referral to an
gynecologic cancer showed that vaginal DHEA led to significant appropriate specialist.913,923 See Treatment of Vaginal Dryness, above, for
improvements in sexual desire, arousal, pain, and overall sexual function, a discussion on the safety of vaginal estrogen.
although a plain moisturizer also improved symptoms.905 In this trial,
Management of ADT-Related Symptoms in Male Survivors
clinically important systemic estrogenic activity was not evident, and the
Survivors of prostate cancer may be on ADT (see the NCCN Guidelines
treatment was safe and well tolerated. Overall, the decision to use local
for Prostate Cancer, available at www.NCCN.org), and may experience
hormones should be individualized with a discussion of the possible risks
many symptoms, including hot flashes, gynecomastia, and anemia.
and benefits. Referral to an appropriate specialist for management can
also be considered. DHEA should be used with caution in survivors with a Vasomotor Symptoms
history of estrogen-dependent cancers. For vasomotor symptoms disruptive to quality of life in men, alternative
ADT options, such as intermittent ADT, can be tried if deemed appropriate
The use of a fractional microablative CO₂ laser has been studied for the
by the oncologist (see the NCCN Guidelines for Prostate Cancer, available
treatment of vaginal dryness and other genitourinary symptoms in
at www.NCCN.org).
postmenopausal women. Significant improvements in symptoms were
observed in as many as 84% of women, although sample sizes are Androgens (eg, testosterone) are used for the relief of hot flashes in men
small.915-917 Limited data also suggest that the laser treatment is effective in who have hypogonadism from chemotherapy or radiation for other
breast cancer survivors.918-921 Studies suggest that adverse events are malignancies. Hormonal options for the relief of hot flashes in survivors on
infrequent and include pelvic pain, vaginal infections, genital herpes ADT include MPA, estrogen, and cyproterone acetate.924-927 Men with
reactivation, and postmenopausal bleeding.915,918,920 However, the FDA vasomotor symptoms should be offered medication for symptomatic
issued a safety communication in July 2018 warning that energy-based improvements. Options include venlafaxine, MPA, cyproterone acetate,
devices such as lasers used for vaginal procedures including the and gabapentin.928
treatment of menopausal symptoms may be associated with serious
adverse events.922 The FDA has not cleared or approved for marketing any The non-hormonal options include the SSRIs venlafaxine and the anti-
energy-based devices for the treatment of menopausal symptoms and convulsant gabapentin. Gabapentin has been shown to be safe and
notes that the safety and effectiveness of these devices for these types of moderately effective at controlling hot flashes in men with prostate cancer
in two randomized controlled trials.929-931 Case reports and small pilot
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studies have shown that venlafaxine may improve hot flash symptoms in low testosterone in survivors of prostate cancer who have no evidence of
men with prostate cancer undergoing ADT.932 The panel lists venlafaxine recurrent disease and are not on ADT is controversial and should be
as the preferred antidepressant and gabapentin as the preferred coordinated with the patient’s primary cancer physician (ie, surgeon,
anticonvulsant for hormone-related symptoms. oncologist, radiation oncologist). Men still receiving ADT should not
receive androgens (eg, testosterone).
As in female cancer survivors, men with ADT-related symptoms can try
non-pharmacologic treatments, including acupuncture, exercise/physical Androgens are contraindicated in men diagnosed with prostate cancer on
activity, yoga, lifestyle modifications, weight loss if overweight or obese, active surveillance or observation, in patients actively being treated for
hypnosis, and CBT.928 Small studies in prostate cancer survivors with a prostate cancer, and in men with advanced prostate malignancy on ADT.
history of ADT have also found that acupuncture is effective at controlling The 2018 AUA Guidelines Committee found insufficient evidence to
hot flashes in this population.933,934 A study of 68 patients with prostate quantify the risk-benefit ratio of testosterone therapy in men with prior
cancer on ADT also found that CBT reduced the perceived burden of hot history of prostate cancer.939 After curative-intent therapies for prostate
flashes compared with usual care.935 cancer, patients should discuss with their surgeon or radiation oncologist
when to resume testosterone (if they had a history of hypogonadism prior
As in women with vasomotor symptoms, phytoestrogens, botanicals, and to treatment of prostate cancer) or when to initiate testosterone therapy for
dietary supplements are often used in males. However, data are limited on hypogonadism.
the effectiveness and safety of these nonpharmacologic treatments in
survivors on ADT.936 Furthermore, there are concerns that supplemental Gynecomastia
vitamin E may increase the risk for prostate cancer.937,938 The panel Gynecomastia and breast pain can be treated in men on ADT by
consensus is that the efficacy and safety data for these treatments are too prophylactic radiation (must be delivered prior to development of breast
limited to make a recommendation for use. tissue), tamoxifen, or reduction mammoplasty.791,940,941
Hypogonadism Anemia
Clinicians should consider measuring free and total testosterone, LH, and Anemia in men on ADT is generally responsive to erythropoietin (EPO) or
prolactin in men with anemia, bone density loss, diabetes, exposure to blood transfusion. These men can be treated as per the NCCN Guidelines
chemotherapy or testicle radiation, HIV/AIDS, chronic narcotic use, for Cancer- and Chemotherapy-Induced Anemia (available at
infertility, pituitary dysfunction, and chronic corticosteroid use.939 Clinicians www.NCCN.org).
should check testosterone levels, even if the patient has a history of
cancer not typically associated with hormonal changes. Diagnosis of Pain
hypogonadism requires two total testosterone measurements taken on More than one-third of post-treatment cancer survivors experience chronic
separate, early-morning blood draws. Testosterone therapy should be pain, which often leads to psychological distress; decreased activity,
discussed when testosterone levels are low (<300 ng/dL) or low normal motivation, and personal interactions; and an overall poor quality of life.942-
and the patient is symptomatic.928 When to initiate or resume treatment for
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Survivorship
946
Pain in survivors is often ineffectively managed. Barriers to optimal pain practice guideline for the management of chronic pain in survivors of adult
management in cancer survivors include health care providers’ lack of cancers.952
training, fear of side effects and addiction, and reimbursement issues.947
Screening for and Assessment of Pain
948,949
Pain has two predominant mechanisms: nociceptive and neuropathic. All cancer survivors should be screened for pain at regular intervals. If
Injury to somatic and visceral structures and the resulting activation of pain is present, the intensity should be quantified by the survivor. Because
nociceptors present in skin, viscera, muscles, and connective tissues pain is inherently subjective, self-report of pain is the current standard of
cause nociceptive pain. Somatic nociceptive pain is often described as care for assessment. Intensity of pain should be quantified using a 0 to 10
sharp, throbbing, or pressure-like, and often occurs after surgical numeric rating scale, a categorical scale, or a pictorial scale (eg, Wong-
procedures. Visceral nociceptive pain is often diffuse and described as Baker FACES Pain Rating Scale).953-956 In addition, the survivor should be
aching or cramping. Neuropathic pain is caused by injury to the peripheral asked to describe the characteristics of the pain (eg, aching, burning).
nervous system or CNS and might be described as numbness or as Severe uncontrolled pain is a medical emergency and should be
burning, sharp, tingling, prickling, electrical, or shooting pain. Neuropathic addressed promptly. In addition, an oncologic emergency should also be
pain often occurs as a side effect of chemotherapy or radiation therapy or ruled out in these cases.
is caused by surgical injury to the nerves.
A comprehensive evaluation, as outlined in the NCCN Guidelines for Adult
The incidence of chronic pain after surgical treatment varies with the type Cancer Pain (available at www.NCCN.org), is essential to ensure proper
of procedure and is as high as 60% in patients treated with breast surgery pain management. The survivor’s goals for comfort and function and the
and 50% in those treated with lung surgery.942 Arthralgias, characterized cause and pathophysiology of the pain should be identified to determine
by joint pain and stiffness, occur in roughly half of women taking the optimal therapeutic strategy. If the pain is new and acute, the
aromatase inhibitors as adjuvant therapy for breast cancer.950 Pelvic pain possibility of pain due to cancer recurrence should be considered. If the
often occurs after pelvic radiation, resulting from fractures, fistulae, pain is chronic, a specific cancer pain syndrome should be identified if
proctitis, cystitis, dyspareunia, or enteritis.942 possible. Referral to a PCP can be made for non-cancer or non-cancer-
treatment–related workup and pain management (ie, rheumatoid arthritis).
These NCCN Guidelines for Survivorship make recommendations for the
management of seven categories of cancer pain syndromes: neuropathic Management of Pain
pain, chronic pain syndromes (ie, pain syndromes after amputation, neck The goals of pain management are to increase comfort, maximize
dissection, mastectomy, thoracotomy), myalgias/arthralgias, skeletal pain, function, and improve quality of life. A multidisciplinary approach, which
myofascial pain, gastrointestinal/urinary/pelvic pain, and postradiation may include a combination of pharmacologic treatments, psychosocial and
pain. Recommendations for the prevention and management of behavioral interventions, physical therapy and physical activity,
chemotherapy-induced peripheral neuropathy (CIPN) in survivors can be occupational therapy, local therapies, and interventional procedures, is
found in ASCO’s clinical practice guideline.951 ASCO also has a clinical recommended.943,957,958 These approaches are discussed in more detail
below. For survivors with refractory pain and/or those who might benefit
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Survivorship
from further pain interventions, referral to a specialist (ie, pain the treatment of neuropathic pain in survivors based on the available data.
management services, interventional specialist, physical therapy, physical Tapentadol is a dual-action mu-opioid agonist/noradrenaline reuptake
medicine, palliative care, rehabilitation, interventional pain, urology, inhibitors.963Two separate randomized controlled trials in patients with
gynecology, orthopedic surgery, gastroenterology, other appropriate painful diabetic peripheral neuropathy (n = 588 and n = 358) showed that
consultants) can also be considered. Finally, psychological support for tapentadol improved pain intensity compared with placebo.964,965 Two other
survivors with chronic pain is necessary, and referral to psychosocial randomized trials in patients with chronic malignant tumor-related pain (n
services should be considered for survivors in distress. = 325 and n = 236) also showed improvements in pain intensity with
tapentadol compared with placebo.966,967 No studies in cancer survivors or
The panel acknowledges the legalization of medical marijuana for various in chemotherapy-induced neuropathy were identified by the panel. Data on
conditions in multiple states. However, there are presently not enough the long-term use of opioids in survivors are lacking.958,960,968 In fact, data
data to make any guideline recommendations regarding use in cancer on the long-term safety and effectiveness of opioids in the non-cancer
survivors. setting are scarce as well.969
For more information about the management of cancer-related pain, Opioid prescribing rates among cancer survivors are substantially higher
please see the NCCN Guidelines for Adult Cancer Pain (available at compared to controls, even long after attaining cancer survivorship.970,971 In
www.NCCN.org). These guidelines include information on opioid use and a retrospective, population-wide cohort study, cancer survivors in Ontario,
controlled substance agreements for patients at risk for medication misuse Canada, diagnosed ≥5 years prior were found to have an adjusted relative
or diversion; adjuvant analgesics; and psychosocial support and rate of opioid prescriptions of 1.22 (95% CI, 1.11–1.34).970 The 3-year
behavioral interventions that may be modified to fit the individual survivor’s mean cumulative number of filled opioid prescriptions was 7.7 in survivors
circumstances. compared with 6.3 in matched controls (P < .0001). Furthermore, a study
of national insurance claims data showed that approximately 10% of
Pharmacologic Interventions
opioid-naïve patients prescribed opioids for curative-intent cancer surgery
Pharmacologic measures are the foundation of treatment of many of the
continued to fill their prescriptions for 90 to 180 days after surgery,
common pain syndromes in survivors. Pharmacologic recommendations in
suggesting that aberrant opioid use or diversion of pain medication may be
these guidelines vary depending on the pain syndrome and include
an issue in the survivor population.972
opioids, adjuvant analgesics, nonsteroidal anti-inflammatory drugs
(NSAIDs), and muscle relaxants.943,959-961 Topical medications are The NCCN Guidelines for Adult Cancer Pain (available at www.NCCN.org)
discussed in Local Therapies, below. recommend screening for risk factors of aberrant opioid use or diversion of
pain medication, using a detailed patient evaluation and/or tools such as
Opioids: Opioids may be recommended for the treatment of neuropathic
the Screener and Opioid Assessment for Patients with Pain-Revised
pain, skeletal pain, and chronic pain syndromes in survivors.962 An opioid
(SOAPP-R) or Opioid Risk Tool (ORT) before prescribing.973-977 Patients
analgesic with a dual mechanism of action as both a mu-opioid agonist
and caregivers should be educated on the potential risks and benefits of
and a noradrenaline reuptake inhibitor is also a recommended option for
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Survivorship
opioid therapy, including the potential for diversion or misuse of opioids systematic review found that antidepressants, anticonvulsants, other
and safe storage and disposal of opioid medications. Various strategies adjuvant analgesics, and opioids were all effective at reducing neuropathic
may be employed to support patients determined to be at high risk for pain in patients with cancer.960 Another review found that antidepressants
opioid misuse; behavioral/cognitive-behavioral interventions, education on and anticonvulsants may provide additional neuropathic pain relief when
naloxone, pain medication diaries/pill counts, and urine drug testing added to opioids in patients with cancer.986
represent just a few of these strategies. Furthermore, the FDA has
established Risk Evaluation and Mitigation Strategy (REMS) programs for Tricyclic antidepressants have been shown to relieve neuropathic pain in
opioid products to reduce addiction, misuse, abuse, overdose, and death the non-cancer setting.987,988 In addition, the SNRI duloxetine was shown to
through provider, patient, and family/caregiver education.978-980 In addition, effectively reduce pain in a multi-institutional, randomized, double-blind,
if opioids are deemed necessary for any survivor (regardless of aberrant placebo-controlled, crossover trial of 231 patients with painful CIPN.989 The
use risk level), the NCCN Survivorship Panel recommends using the ASCO clinical practice guidelines for the prevention and management of
lowest dose possible for the shortest period of time possible and CIPN in survivors of adult cancers recommend duloxetine in this setting.951
reevaluating the effectiveness and necessity of opioids on a regular basis. Duloxetine can also improve aromatase inhibitor-associated arthralgia. A
Pain treatment agreements can also be considered.981 randomized, double-blind, placebo-controlled, phase III trial, which
included 299 postmenopausal survivors of early-stage breast cancer with
In March 2016, the CDC released guidelines for prescribing opioids for joint pain, showed that duloxetine improved average joint pain score, worst
chronic pain.982 In May 2016, ASCO released a policy statement, pain, joint stiffness, pain interference, and functioning at 12 weeks.990
describing principles to help balance concerns for the abuse and misuse SNRIs are therefore listed as a category 1 recommendation for survivors
of opioids with concerns for appropriate access of opioids for pain with aromatase inhibitor-induced arthralgia.
management in patients with cancer and survivors.983 The NCCN
Survivorship Panel shares these concerns and supports ASCO’s The most commonly used anticonvulsant drugs for the treatment of
statement. Overall, the panel believes that the concerns for the abuse and cancer-related pain are gabapentin and pregabalin. They are
misuse of opioids must be balanced with concerns for appropriate access recommended in these guidelines for the treatment of myalgias and
of opioids for pain management in patients with cancer and survivors.983-985 arthralgias.991 Both drugs have also demonstrated efficacy in diabetic and
postherpetic neuropathy,992-994 but have not been well-studied in the cancer
Adjuvant Analgesics: Adjuvant analgesics include antidepressants (eg, or survivorship settings.951 One randomized, placebo-controlled, crossover
SNRIs, tricyclic antidepressants) and anticonvulsants (eg, gabapentin, trial in 115 survivors found that gabapentin did not effectively treat CIPN.995
pregabalin).962 These are recommended for the treatment of survivors with However, because high-level evidence is limited to this one trial, the panel
neuropathic pain, post-radiation pain, chronic pain syndromes, myalgias, concurs with ASCO’s CIPN panel and believes that extrapolation from
and arthralgias. The term adjuvant refers to the fact that they are often co- other neuropathic pain conditions is reasonable and that gabapentin can
administered with an opioid to enhance analgesia or reduce the opioid be offered to select survivors with CIPN after informing them about the
requirement, but they may also be used as the sole pain treatment. A inconclusiveness of the evidence and of potential harms, benefits, and
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Survivorship
costs.951 A randomized, double-blind trial of pregabalin compared with Psychosocial Support and Behavioral Interventions
placebo in 128 patients with neuropathic pain following radiation therapy Cognitive interventions are aimed at enhancing a sense of control over the
for head and neck cancer found that pregabalin reduced pain scores to a pain or its underlying cause. Breathing exercises, relaxation, imagery or
greater extent than placebo.996 A ≥30% pain relief was achieved by 59% hypnosis, and other behavioral therapies can be very useful.944,1001-1006 A
versus 33% of participants (P = .006), and a ≥50% pain relief was randomized controlled trial of 129 breast cancer survivors with pain found
achieved by 30% versus 8% (P = .003). that an 8-week mindfulness-based cognitive therapy program reduced
pain intensity and nonprescription pain medication use compared with a
Corticosteroids are not recommended for the management of pain in waitlist control group.1007 Quality of life was also improved in the
cancer survivors. A randomized, placebo-controlled, double-blind trial of
intervention arm, but distress was not reduced.
adult patients with advanced cancer receiving opioids found that
methylprednisolone did not provide additional analgesia over that provided Psychosocial support and education should also be provided.1008 Some
by the opioids.997 studies in patients with cancer suggest that psychosocial and behavioral
interventions such as skills training, education, relaxation training,
Nonsteroidal Anti-Inflammatory Drugs: NSAIDs, including COX-2
supportive–expressive therapy, and CBT may be effective at reducing
inhibitors, and acetaminophen are recommended for the treatment of pain.1003,1009 Hypnosis can also be considered for treatment of neuropathic
myofascial, skeletal, and post-radiation pain, and for myalgias and
pain. Overall, data support the benefit of hypnosis for controlling pain in
arthralgias. NSAIDs are non-opioid analgesics that block the biosynthesis
cancer and other settings, but are lacking in the survivorship
of prostaglandins, which are inflammatory mediators that can initiate,
population.1010
cause, intensify, or maintain pain. A systematic review found that data
supporting the use of NSAIDs for control of pain in patients with advanced Mirror therapy, if available, can be considered for the treatment of chronic
cancer are limited and weak, but suggest some efficacy at reducing pain “phantom limb” pain after amputation. In mirror therapy the survivor views
and opioid dose requirement.998 a reflected image of his or her intact limb in a mirror while trying to move
the amputated limb. In a small randomized trial, mirror therapy reduced
A discussion of contraindications and safety precautions that should be
pain in 6 of 6 patients and in 8 of 9 patients who switched to mirror therapy
considered before prescribing NSAIDs is provided in the NCCN Guidelines
from the control conditions (covered mirror or mental visualization).1011 One
for Adult Cancer Pain (available at www.NCCN.org). case report suggests that this therapy can be effective in survivors.1012
Muscle Relaxants: Muscle relaxants (eg, diazepam, lorazepam,
In general, studies regarding psychosocial support and behavioral
metaxalone) reduce muscle spasms and are recommended for the
interventions for reducing pain in survivors are limited. A systematic review
treatment of skeletal pain, myalgias, and arthralgias. Evidence for their
and meta-analysis assessed the efficacy of psychosocial interventions for
efficacy in providing pain relief in the non-cancer setting is limited.999,1000 No
treating pain in patients with breast cancer and survivors.1013 Although
data could be found in the setting of cancer-related pain.
results suggest an effect, more studies are clearly needed in the
survivorship population.
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Physical Therapy and Physical Activity recommended for myofascial pain. Compounded creams containing
Physical therapy and general physical activity may also be effective for the agents such as lidocaine, capsaicin, baclofen, ketamine, and amitriptyline
treatment of pain in survivors, with the main goal of increasing are recommended for treatment of neuropathic pain. Use of
mobility.210,944,957,1014 Several randomized controlled trials have reported a transcutaneous electrical nerve stimulation (TENS) can be used for
reduction of neck and shoulder pain associated with exercise or therapy neuropathic pain and for chronic post-mastectomy and post-thoracotomy
programs.1015-1019 In one study, 52 survivors of head and neck cancer were pain.
randomized to a progressive resistance exercise training (PRET) program
Data are limited on the effectiveness of ketamine and amitriptyline,1021-1026
or standard therapeutic exercise for 12 weeks.1017 Pain scores decreased
but the evidence for the effectiveness of lidocaine and capsaicin is
more dramatically in the PRET group (P = .001). In another study of 66
stronger.1021,1023-1025 In a randomized trial of 208 participants with CIPN, the
survivors of breast cancer, those randomized to an 8-week water exercise
group that received a compounded topical gel containing baclofen,
program experienced a greater reduction of neck and shoulder pain than
those randomized to usual care.1015 A more recent randomized trial amitriptyline, and ketamine showed a trend towards improvements in the
sensory and motor subscales of the EORTC QLQ-CIPN20 compared with
showed that breast cancer survivors with aromatase-inhibitor–induced
the placebo group.1027 The greatest improvements were seen in tingling,
arthralgia randomized to an exercise arm (150 min/wk of aerobic exercise
cramping, shooting/burning pain in the hands, and difficulty holding a pen.
plus supervised strength training twice per week) experienced greater
Lidocaine has been shown to reduce the severity of postherpetic
improvements in worst joint pain scores, pain severity, and pain
neuropathy and cancer-related pain.1028,1029 In a randomized trial of 35
interference than those in the usual care arm (all P < .001).1018 Physical
patients with non–cancer-related postherpetic, postoperative, or diabetes-
activity is thus listed as a category 1 recommendation for survivors with
related neuropathic pain, pain intensity was reduced with topical lidocaine
aromatase inhibitor-induced arthralgia.
but not with topical amitriptyline when compared with placebo.1024 A larger
In addition, group exercise in the community with trainers specifically trial with a similar population of 92 patients found no effect of topical
trained to work with cancer survivors has been shown to reduce pain and amitriptyline, ketamine, or a combination of the two.1030 Another study
other symptoms.291 Yoga may also be helpful for pain management in found that a higher dose of amitriptyline had some efficacy in reducing
cancer survivors. In a randomized controlled trial of 167 breast cancer peripheral neuropathy, but also showed systemic effects.1031 More
survivors on aromatase inhibitors or tamoxifen, yoga reduced recently, results of a multicenter, phase III, randomized, double-blind,
musculoskeletal pain symptoms.1020 placebo-controlled trial of 462 survivors with CIPN found that
ketamine/amitriptyline cream had no effect.1032 Similarly, a randomized trial
Local Therapies that included 133 patients with non-cancer neuropathic pain found that
Local therapies, including heat, cold packs, massage, and medicated compounded cream containing ketamine, gabapentin, clonidine, and
creams, ointments, and patches, are recommended for the treatment of lidocaine was no more effective than placebo at reducing the average pain
myalgias, arthralgias, and neuropathic pain.944 Specifically, topical score 1 month after treatment.1033
ointments (ketamine) and patches (ie, lidocaine, capsaicin) are
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Survivorship
TENS is a noninvasive procedure in which electrodes are placed on or nerve blocks, neurotomy with radiofrequency ablation, and dorsal column
around the painful area.944 A systematic review demonstrated that data stimulation are some of the options that can be considered.
supporting the efficacy of TENS for reducing cancer-related pain are
inconclusive.1034 The goal of invasive interventions, such as an intercostal Sexual Dysfunction
nerve block, is to interrupt nerve conduction by either destroying nerves or Cancer treatment, especially hormonal therapy and surgical and/or
interfering with their function.944 The data on these interventions are also radiation therapy directed towards the pelvis, can often impair sexual
limited.944 function. In addition, depression and anxiety, which are common in
survivors, can contribute to sexual problems. Thus, sexual dysfunction is
Acupuncture common in survivors and can cause increased distress and have a
Acupuncture is recommended as a possible option for the treatment of significant negative impact on quality of life.1041-1046 Nonetheless, sexual
myofascial or neuropathic pain in survivors. Evidence supporting the function is often not discussed with survivors.1047-1051 Reasons for this
efficacy of this technique for reducing cancer-related pain is evolving.1035- include a lack of training of health care professionals, discomfort of
1037
A small randomized controlled trial compared electro-acupuncture (EA) providers and/or survivors with the topic, survivors’ perception of
to white light cystoscopy (WLC) and sham acupuncture in 67 discomfort from the provider, and insufficient time during visits for
postmenopausal women with breast cancer and aromatase inhibitor- discussion.1041 However, effective strategies for treating both female and
associated arthralgia.1038 Pain severity was improved in both the EA and male sexual dysfunction exist, making these discussions a critical part of
sham acupuncture arms compared with the control arm (mean reduction in survivorship care.
pain severity in the EA vs. WLC groups at week 8, -2.2 vs. -0.2; P =
.0004). Another trial randomized 226 postmenopausal women with early- Panel recommendations for the management of sexual dysfunction in
stage breast cancer and AI-induced joint pain 2:1:1 to acupuncture, sham survivors are described herein. Cancer Care Ontario has developed
acupuncture, or waitlist.1039 The acupuncture group experienced a small recommendations for the management of sexual problems in patients with
but statistically significant reduction in joint pain at 6 weeks. Acupuncture cancer that ASCO has endorsed.928,1052 Most of their recommendations are
is thus listed as a category 1 recommendation for survivors with consistent with those put forth by the NCCN Survivorship Panel.
aromatase inhibitor-induced arthralgia. Neuropathic pain was also reduced
NCCN is aware that many regenerative, restorative, or rejuvenation
with acupuncture in a small randomized trial of 40 breast cancer survivors
therapies are being marketed to patients with sexual dysfunction.
with CIPN.1040
Survivors should be aware that the FDA has not approved injections of
Management of Refractory Pain autologous platelet-rich plasma or stem cells for treatment of male sexual
For refractory pain, referral to pain management services, an dysfunction. The FDA has not cleared energy-based devices (ie, vaginal
interventional specialist, physical therapy, physical medicine and rejuvenation by lasers or erectile dysfunction [ED] by shock waves, also
rehabilitation, and/or palliative care should be considered. Intercostal discussed in Treatment of Vaginal Dryness, above and Interventions for
Male Sexual Dysfunction, below) for treatment of menopausal changes,
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ED, or incontinence. Cancer survivors with sexual dysfunction should be Some of the sexual dysfunction associated with HSCT is related to GVHD,
referred to specialists for discussions of non–FDA-approved therapeutics which can result in vaginal fibrosis, stenosis, mucosal changes, vaginal
and special consideration should be given to their primary diagnosis of irritation, bleeding, and increased sensitivity of genital tissues.1066,1068 In
cancer prior to enrollment in clinical trials for sexual dysfunction or addition, high-dose corticosteroids used for chronic GVHD can increase
incontinence. emotional lability and depression, affecting feelings of attractiveness,
sexual activity, and quality of sexual life.
Female Sexual Dysfunction
Female sexual problems relate to issues with sexual desire, arousal, Male Sexual Dysfunction
orgasm, and pain.1053-1055 Sexual dysfunction after cancer treatment is The NIH Consensus Conference on Impotence defined impotence as
common in female survivors.30,1045,1056-1061 A survey of 221 survivors of "male erectile dysfunction, that is, the inability to achieve or maintain an
vaginal and cervical cancer found that the prevalence of sexual problems erection sufficient for satisfactory sexual performance."1069 In fact,
was significantly higher among survivors than among age- and race- impotence and ED are not synonymous. Impotence can involve problems
matched controls from the National Health and Social Life Survey (mean of sexual desire, orgasm, or ejaculation, which are not necessarily linked
number of problems 2.6 vs. 1.1; P < .001).1060 A survey of survivors of with achieving or maintaining an erection.1070
ovarian germ cell tumors and age- and race- and education-matched
controls found that survivors reported a significant decrease in sexual ED associated with a cancer diagnosis and cancer therapy may have a
pleasure.1062 psychologic component, but is most often physiologic and iatrogenic. In
the case of surgery, ED may be immediately evident; in the case of
Female sexual dysfunction varies with cancer site and treatment radiation treatments, presentations can be delayed. ED occurs frequently
modalities.1057,1058 For example, survivors of cervical cancer who were in the general population and increases with age.1071 In one community-
treated with radiotherapy had worse sexual functioning scores (for arousal, based study, 33% of men aged ≥75 years reported moderate or worse
lubrication, orgasm, pain, and satisfaction) than those treated with surgery, ED.1072 ED is also very common in male cancer survivors. Anticancer
whose sexual functioning was similar to that of age- and race-matched treatment modalities used in a variety of cancers have the potential to
non-cancer controls.1057 A systematic review of sexual functioning in damage blood vessels, leading to a reduction in blood circulation to the
cervical cancer survivors found similar results, except that no differences penis and/or damage to the autonomic nervous system. Thus, higher rates
in orgasm/satisfaction were observed.1063 Chemotherapy seems to be of ED are seen in cancer survivors than in the general population. The
linked to female sexual dysfunction in breast cancer survivors,1058 possibly prevalence of ED in male survivors of colorectal cancer has been reported
related to the prevalence of chemotherapy-induced menopause in this to range from 45% to 75%,1042,1073,1074 and it has been reported in up to 90%
population.1054 Furthermore, body image changes related to breast cancer of survivors of prostate cancer.1075-1079
surgery and reconstruction can affect women’s sexual health and well-
being.1064 In addition, survivors with a history of HSCT may have multiple Male cancer survivors exposed to radiation or chemotherapy often
types of sexual dysfunction even 5 to 10 years after diagnosis.1065-1067 experience hypogonadism—usually primary hypogonadism.
Hypogonadism in men refers to a decrease in the production of sperm
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and/or testosterone. Primary hypogonadism is the result of testicular interested. These survivors should also be re-evaluated and engaged in
failure. In these men testosterone levels and sperm counts are below discussions about the potential impact of treatment on sexual function at
normal, and serum LH and FSH are above normal. Secondary future visits.
hypogonadism is a disease of the pituitary or hypothalamus. In men with
secondary hypogonadism, serum testosterone levels and sperm counts For survivors who want to discuss their sexual function further, screening
are subnormal, and the serum LH and FSH levels are normal or reduced. tools can be considered. Several screening tools are available for both
Adult-onset hypogonadism is characterized by a deficiency of testosterone men and women. For women, options include the Brief Sexual Symptom
and a failure of the body to produce an adequate compensatory response. Checklist for Women, the Arizona Sexual Experience Scale (ASEX), the
In these men, low testosterone levels are associated with normal or low Female Sexual Function Index (FSFI), and a breast cancer-specific
levels of gonadotropins, suggesting physiologic failure of both the testicles adaptation of the FSFI (FSFI-BC).1086-1089 For men, the Sexual Health
and hypothalamic-pituitary system.1080 Inventory for Men (SHIM), the Sexual Quality of Life Questionnaire-Men,
and the PROMIS Brief Function Profile-Male are examples.1071,1090,1091 The
Evaluation and Assessment for Sexual Function FSFI has been validated in patients with cancer and cancer
All adult cancer survivors, regardless of gender identity and sexual survivors.1092,1093 The FSFI and ASEX were also identified in a systematic
orientation, should be asked about their sexual function at regular review as tools that have acceptable psychometric properties in patients
intervals, by inquiring about any concerns or distress regarding sexual with breast cancer.1094 The other tools have not been validated in cancer or
function, sexual activity, sexual relationships, or sex life. Cancer survivors survivor populations.
who report distress should be evaluated further. Inquiries into treatment-
related infertility should be made if indicated, with referrals as appropriate. Survivors with concerns about their sexual function should undergo a
ASCO’s recently updated clinical practice guidelines on fertility more thorough evaluation, including screening for possible psychosocial
preservation for patients with cancer have more information on the problems or mental health issues (ie, anxiety, depression, relationship
topic.1081 It is important for providers to be aware that fertility issues should issues, body image concerns, drug or alcohol use) that can contribute to
be addressed in the survivorship phase, whether or not they were sexual dysfunction. It is also important to identify prescription and over-
addressed prior to treatment.1082-1084 A discussion regarding the need for the-counter medications (especially hormone therapy, narcotics, beta-
contraception may also be helpful in some cases, because the incidence blockers, and SSRIs) that could be a contributing factor. Traditional risk
of unplanned pregnancies is approximately three times higher in cancer factors for sexual dysfunction, such as CVD, diabetes, obesity, smoking,
survivors than in the general population.1085 and alcohol abuse, should also be assessed, as should the patient’s
oncologic and treatment history. In addition, the impact of cancer and
Survivors for whom screening does not indicate an issue with sexual cancer treatment on sexual function should be explored further. Finally, for
function should be rescreened at subsequent visits. For survivors with men, total morning testosterone should be measured if indicated by
sexual function concerns who do not wish to discuss them at the current concerns regarding hypogonadism.800
visit, referral can be made to a sexual health specialist if the survivor is
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Interventions for Female Sexual Dysfunction Vaginal moisturizers, vaginal gels, oils, and topical vitamin D or E can help
Female sexual dysfunction is often multifactorial in nature. Therefore, alleviate symptoms such as vaginal dryness and sexual pain,901,1099
treatment of sexual dysfunction often requires a multidimensional although data on these over-the-counter products are limited in the
treatment plan that addresses the underlying issues, which can be general population (also see Treatment of Vaginal Dryness, under
physiologic (eg, menopause, illness), disease-induced, medication- Hormone-Related Symptoms above). Topical anesthetics may help with
induced, psychologic (eg, anxiety, depression), and interpersonal. vaginal pain as shown in a study in 46 breast cancer survivors that found
Informed patient and physician decision-making is the standard for guiding that application of lidocaine to the vulvar vestibule before vaginal
treatment decisions for treatment of female sexual dysfunction. Referrals penetration improved dyspareunia.1100
to specialists (ie, psychotherapy, sexual/couples counseling, gynecologic
care, sexual health specialist) should be made if appropriate and Pelvic physical therapy (ie, pelvic floor muscle training) may improve
available. sexual pain, arousal, lubrication, orgasm, and satisfaction. A small study of
34 survivors of gynecologic cancers found that pelvic floor training
Overall, the evidence base for interventions to treat female sexual significantly improved sexual function.1101
dysfunction in survivors is weak and high-quality studies are
needed.1095,1096 Based on evidence from other populations, evidence from Vaginal dilators are an option for survivors with pain during sexual activity.
survivors when available, recommendations from the American College of In addition, vaginal dilators are used for survivors with vaginal stenosis
Obstetricians and Gynecologists (ACOG),1053 and consensus among from pelvic radiation. However, evidence for the effectiveness of dilators is
NCCN Survivorship Panel Members, the panel made recommendations limited.1102
for treatment of female sexual dysfunction in survivors. The panel
Several topical prescription medications can also be considered for female
recommends that treatment be guided by the specific type of problem.
survivors with sexual dysfunction (also see Treatment of Vaginal Dryness,
Treatments depend on the type of sexual dysfunction and may include
under Hormone-Related Symptoms above). For example, vaginal
both over-the-counter and prescription options, as well as pelvic physical
estrogen (pills, rings, or creams) has been shown to be effective in treating
therapy and integrative therapies. When prescription medications are
vaginal dryness, itching, discomfort, and painful intercourse in
being considered, the risks and benefits should be discussed, or the
postmenopausal women.881,906-910 A study in 76 postmenopausal breast
survivor should be referred to an appropriate health care provider (eg,
cancer survivors on aromatase inhibitor therapy found that intravaginal
sexual health specialist) for prescription and/or treatment. The evidence
testosterone cream or an estradiol-releasing vaginal ring were safe and
base for each recommendation is described herein.
improved vaginal atrophy and sexual function.1103 The panel notes that
Integrative therapies, including yoga and meditation, may be helpful for focal application of creams applied to external vulvar regions are absorbed
female survivors with sexual dysfunction.857,1097 In addition, CBT has been to a lesser degree than creams placed inside the vagina.
shown to be effective at improving sexual functioning in breast cancer
Vaginal androgens (ie, DHEA; also known as prasterone) can be
survivors.1098
considered for vaginal dryness or pain with sexual activity (also see
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Treatment of Vaginal Dryness, under Hormone-Related Symptoms In August 2015, the FDA approved flibanserin to treat acquired,
above). Vaginal DHEA received FDA approval in 2016. Several studies generalized hypoactive sexual desire disorder (HSDD) in premenopausal
have shown it to be effective at reducing dyspareunia in postmenopausal women.1116 Meta-analyses have shown that flibanserin resulted in
women.1104-1108 However, a systematic review and meta-analysis published approximately 1 additional satisfying sexual event every 2 months in
in 2015 concluded that it is uncertain whether vaginal DHEA improves premenopausal women.1117,1118 This drug has not been studied in patients
vasomotor symptoms and vaginal dryness.1109 A randomized controlled with cancer or survivors, but it is a reasonable option to discuss with
trial of 464 survivors of breast or gynecologic cancer showed that vaginal premenopausal survivors with low or lack of desire, libido, or intimacy.
DHEA led to significant improvements in sexual desire, arousal, pain, and
overall sexual function, although a plain moisturizer also improved In June 2019, the FDA approved bremelanotide for the treatment of
symptoms.905 In this trial, clinically important systemic estrogenic activity premenopausal women with acquired, generalized HSDD as characterized
was not evident, and the treatment was safe and well tolerated. Overall, by low sexual desire that causes marked distress or interpersonal difficulty
safety data for the use of androgen-based therapy in survivors of and is not due to 1) a coexisting medical or psychiatric condition; 2)
hormonally mediated cancers are limited. The FDA label for vaginal DHEA problems with the relationship; or 3) the effects of a medication or drug
warns that exogenous estrogens are contraindicated in women with a substance.1119 The safety and efficacy of bremelanotide in premenopausal
history of breast cancer.1110 The panel cautions that DHEA should be used women with HSDD was evaluated in two phase 3, randomized, double-
with caution in survivors with a history of estrogen-dependent cancers. blind, placebo-controlled, multicenter clinical trials (RECONNECT; BMT-
301, and BMT-302).1120 Bremelanotide administered subcutaneously as
In 2013, the FDA approved the SERM ospemifene for treating moderate to needed was generally well tolerated, with nausea, flushing, and headache
severe dyspareunia in postmenopausal women without known or (mild-to-moderate in most participants) reported more frequently than in
suspected breast cancer and without a history of breast cancer.1111 patients taking placebo. Women in the bremelanotide group experienced a
Ospemifene has been studied in several large trials of women with statistically significant increase in sexual desire (BMT-301: 0.30, P < .001;
postmenopausal vulvar and vaginal atrophy and was found to effectively BMT-302: 0.42, P < .001) and a statistically significant reduction in
treat vaginal dryness and dyspareunia.1112-1114 Data in the survivor distress related to low sexual desire (BMT-301: -0.37, P < .001; BMT-302:
population are very limited. One prospective study, in which 52 survivors -0.29, P = .005) compared with placebo. Bremelanotide has not been
of stage I–IIa cervical cancer with vulvovaginal atrophy were treated with studied in cancer survivors, but the panel believes it may be an
ospemifene, found improvements in vaginal health and function, sexual appropriate option for some survivors with HSDD.
activity, body image, sexual enjoyment, global health status, and
emotional and social functioning.1115 The panel recommends consideration Other options for female survivors with low or lack of desire, libido, or
of ospemifene for dyspareunia in survivors of cancers that are not intimacy include bupropion and buspirone.1121 These drugs have been
hormonally sensitive. studied in a few trials involving non-cancer populations.1122-1124 Despite
limited safety and efficacy data, these drugs may be considered as options
for HSDD.
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Currently, the panel does not recommend the use of oral In addition, treatment of psychosocial problems, with referral to sex and
phosphodiesterase type 5 inhibitors (PDE5i) for female sexual dysfunction couples therapy as appropriate, can often alleviate symptoms of male
because of the lack of data regarding their effectiveness in women. sexual dysfunction.1138-1142 Small studies in survivors of prostate cancer
Although thought to increase pelvic blood flow to the clitoris and suggest that these approaches can be helpful in the survivorship
vagina,1125,1126 PDE5i showed contradictory results in randomized clinical population as well.1143,1144 Therapy is often offered in conjunction with
trials of various non-cancer populations of women being treated for sexual medical therapy.
arousal disorder.1127-1132 More research is needed before a
recommendation can be made regarding the use of sildenafil for the PDE5i treatment has been shown to improve the symptoms of ED and be
treatment of female sexual dysfunction. well tolerated.1145,1146 The 2017 ASCO Practice on Interventions to Address
Sexual Problems in People with Cancer recommends PDE5i medications
Interventions for Male Sexual Dysfunction be used to help men with ED.928 Many studies have also shown the
Using a consensus-based approach, the NCCN Survivorship Panel efficacy and tolerability of PDE5i for treating ED in patients with cancer
concluded that: 1) informed patient and physician decision-making is the and survivors.1147,1148 Importantly, PDE5i are contraindicated in patients
standard for guiding treatment decisions for treatment of male sexual taking oral nitrates, because together they can lead to a dangerous
dysfunction; and 2) a psychological overlay frequently exists in patients decrease in blood pressure.1149,1150 The timing and dose of on-demand
with sexual dysfunction and may be even more pronounced in the face of PDE5i should be started conservatively, and it should be titrated to the
cancer survivorship. Thus, treatment of male sexual dysfunction may maximum dose as needed.1070 Survivors on PDE5is should be monitored
require a multidimensional treatment plan that addresses the underlying periodically for efficacy, side effects, and any significant change in health
issues. Referrals to specialists (ie, psychotherapy, sexual/couples status. In addition to on-demand PDE5i treatment, studies have shown
counseling, urology, sexual health specialist) should be made if that daily, low-dose treatment with these drugs can be effective.1151-1154
appropriate and available. Treatment of sexual dysfunction in male
survivors should be guided by the specific type of problem. If total morning testosterone is <300 ng/dL, then hypogonadism is
diagnosed and testosterone therapy may relieve symptoms of ED,
Treatment for male sexual dysfunction should include modification of risk problems with ejaculation, or problems with orgasm.1155 A randomized
factors, such as smoking cessation, weight loss, increasing physical controlled trial in 470 men older than 65 years of age with testosterone
activity, and avoiding excess alcohol consumption. Several trials have levels <275 ng/dL found that testosterone gel led to improvements in
shown that such lifestyle modifications can improve sexual function in sexual function, desire, and activity.1156,1157 Other studies have shown that
men.1133-1136 In fact, one study found that PDE5i treatment with an aerobic the addition of testosterone to PDE5i therapy in men with low serum
activity program was more effective than PDE5i treatment alone in 60 men testosterone levels helps improve ED.1158-1163 Testosterone therapy should
with ED.1137 Evidence for these effects in patients with cancer and not be used if contraindicated by the primary oncologic diagnosis (eg,
survivors is lacking. prostate cancer on active surveillance, prostate cancer on ADT).
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Other treatments may help with ED and with ejaculation and orgasm often in combination with pain, fatigue, anxiety, and/or depression.1173-1184
issues. Although evidence in the general population is lacking,1164 studies In fact, sleep disorders have been shown to be a risk factor for suicide.536
in prostate cancer survivors suggest that pelvic physical therapy (ie, pelvic Improvements in sleep quality lead to improvements in fatigue, mood, and
floor muscle training) may improve sexual function in this population.1165,1166 overall quality of life.717 Most clinicians, however, do not know how best to
Vibratory therapy may reduce problems with premature ejaculation.1167 evaluate and treat sleep disorders.1173
Cancer therapies can result in a variety of ejaculatory dysfunctions
(premature, absent, delayed, or climacturia), and these are best Sleep disorders are common in patients with cancer as a result of multiple
addressed with urology specialist consultation.1168-1171 factors, including disease- or treatment-related biologic changes in sleep
and wake regulation, the stress of diagnosis and treatment, and side
Survivorship caregivers should be aware that “restorative or regenerative” effects of therapy (eg, pain, fatigue).1185 In addition, evidence suggests that
therapies for ED are being widely advertised in the United States, but, as changes in inflammatory processes from cancer and its treatment play a
of the publication of these NCCN Guidelines, none of these treatments role in sleep disorders. These sleep disturbances can be perpetuated in
has been approved or cleared by the FDA for the treatment of ED. the survivorship phase by chronic side effects, anxiety, depression,
Survivors should be made aware that regenerative therapies for ED are medications, and maladaptive behaviors such as shifting sleep times,
being administered in cash-only practices. The Sexual Medicine Society of excessive time in bed because of fatigue, and unplanned naps.1185
North America position statement on regenerative therapies for ED
concludes: “given the current lack of regulatory agency approval for any Additional information about sleep disorders in patients with cancer can be
restorative (regenerative) therapies for the treatment of ED and until such found in the NCCN Guidelines for Palliative Care and the NCCN
time as approval is granted, SMSNA believes that the use of shock waves Guidelines for Cancer-Related Fatigue (available at www.NCCN.org).
or stem cells or platelet rich plasma is experimental and should be These guidelines may be modified to fit the individual survivor’s
conducted under research protocols in compliance with Institutional circumstances.
Review Board approval. Patients considering such therapies should be
Screening for and Assessment of Sleep Disorders
fully informed and consented regarding the potential benefits and risks.
Survivors should be screened for possible sleep disorders at regular
Finally, the SMSNA advocates that patients involved in these clinical trials
intervals, especially when they experience a change in clinical status or
should not incur more than basic research costs for their participation.”1172
treatment. The panel lists screening questions that can help determine
Sleep Disorders whether concerns about sleep disorders or disturbances warrant further
assessment. Other tools to screen for sleep problems have also been
Sleep disturbances include insomnia (trouble falling or staying asleep
validated and may be used for individual intensive screening to assess
resulting in daytime dysfunction), excessive sleepiness (which can result
sleep quality.1186-1189 It is important to note that survivors may have more
from insufficient sleep opportunity, insomnia, or other sleep disorders),
than 1 sleep disorder simultaneously.
and sleep-related movement or breathing disorders.1173 Sleep disturbances
are common, affecting 30% to 50% of patients with cancer and survivors,
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The panel recommends that sleep/wake timing and/or sleep logs or diaries questionnaire can be used as a screening tool to determine the risk of
be reviewed. Many survivors may be using wearable devices to track OSA.1196 Other screening tools for OSA risk have also been
sleep. However, studies have shown that these devices do not accurately validated.1197,1198 Sleep studies can confirm the diagnosis of OSA;
measure sleep when compared to results of polysomnography.1190-1195 alternatively, referral can be made to a sleep specialist or PCP for further
Results from wearable devices may be useful for tracking sleep patterns, evaluation. Narcolepsy should be considered when excessive sleepiness
but should not be used for diagnosis or clinical decision-making. is accompanied by cataplexy. Parasomnias (eg, sleep walking, sleep
paralysis, periodic limb movement disorder) and circadian rhythm
If concerns regarding sleep quality are significant, the panel recommends disorders (eg, shift work sleep disorder, advanced or delayed sleep phase
that treatable or modifiable contributing factors be assessed and disorders) should also be considered; survivors with these types of sleep
managed. Comorbidities that can contribute to sleep problems include disturbances may also present with symptoms of insomnia.
alcohol and substance abuse, obesity, cardiac dysfunction, endocrine
dysfunction, respiratory disorders, anemia, neurologic disorders (including Excessive sleepiness can also be associated with uncomfortable
CIPN), pain, fatigue, and emotional distress. Screening for common sleep sensations or an urge to move the legs (and sometimes the arms or other
disorders such as obstructive sleep apnea (OSA), restless legs syndrome body parts). These symptoms are usually worse at night and with
(RLS, also known as Willis-Ekbom disease), and circadian rhythm sleep inactivity, may be improved or relieved with movement such as walking or
wake disorders (such as shift work) can help identify specific therapies for stretching, and indicate RLS. In these individuals, a history and physical
these conditions that may be helpful. In addition, some medications, both exam should be performed, with evaluation for iron deficiency if RLS is
prescription and over-the-counter, can contribute to sleep issues. For diagnosed.1199,1200 Alternatively, referral can be made to a sleep specialist
instance, pain medication, antiemetics, antihistamines, antidepressants, or PCP for further evaluation.
and antipsychotics can all contribute to sleep disturbance, as can the
Evaluation for Insomnia
persistent use of sleep aids.
If insomnia is diagnosed, details should be obtained regarding the course
Diagnosis of Sleep Disorders of insomnia, including the duration of symptoms. Insomnia is considered to
The panel divided sleep disorders into two general categories: 1) be chronic if symptoms have been ongoing for ≥3 months. It should also
insomnia; and 2) sleep disturbance and/or excessive sleepiness. Insomnia be determined whether or not the insomnia symptoms are causing
is diagnosed when patients have difficulty falling asleep, staying asleep, or distress, impacting daytime functioning, or affecting the survivor’s quality
waking up too early at least 3 times per week for at least 4 weeks. These of life.
categories were based on the most common types of symptoms that
Management of Sleep Disorders
patients with sleep disturbances are likely to report.
In all cases, comorbidities that may be contributing to the sleep disorder
Diagnosing patients with excessive sleepiness can be challenging, should be addressed. Survivors should also be advised that sleepiness
because it can be caused by a variety of factors. When excessive can increase the risk of accidents, including while operating a motor
sleepiness is associated with observed apneas or snoring, the STOP vehicle. In addition, several types of interventions are recommended, as
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described below.1173,1201,1202 Referral to a sleep specialist can be considered limited.1215 Another randomized controlled trial assessed the effects of a 3-
in most cases, especially for OSA, RLS, parasomnias, circadian rhythm month physical activity behavior change intervention on 222 breast cancer
disorders, narcolepsy, and chronic or refractory insomnia. Referral to a survivors.1216 Participants in the intervention arm experienced significant
PCP can also be considered, except in cases of circadian rhythm disorder, improvement in self-reported global sleep quality at 3 and 6 months.
prolonged wakefulness or awakenings, prolonged nocturnal sleep (ie, >9 However, actigraphy results showed no differences between the
hours for adults), cataplexy, frequent short naps, vivid dreams, disrupted intervention and usual care arms. Overall, data supporting improvement in
sleep, or sleep paralysis, in which cases a sleep specialist is sleep with physical activity are limited in the survivorship population.
recommended.
Psychosocial Interventions
Sleep Hygiene Education Cognitive behavior treatments such as CBT-I, iCBT, relaxation therapy,
Educating survivors about general sleep hygiene is recommended, stimulus control, and sleep restriction are recommended to treat sleep
especially for the treatment of circadian rhythm disorders, insomnia, and disturbances in survivors.1217-1219 These approaches are preferred over
excessive sleepiness associated with insufficient sleep time.1203-1205 Key pharmacologic interventions as first-line therapy.
points are listed in the guidelines and include regular morning or afternoon
physical activity; daytime exposure to bright light; keeping the sleep Several randomized controlled trials have shown that CBT improves sleep
environment dark, quiet, and comfortable; and avoiding heavy meals, in the survivor population.706-708,716,1220-1222 For example, a randomized
moderate to strenuous physical activity, alcohol, and nicotine near controlled trial in 150 survivors (58% breast cancer; 23% prostate cancer;
bedtime. However, sleep hygiene alone is insufficient for the effective 16% bowel cancer; 69% women) found that a series of 5 weekly group
management of sleep disorders. CBT sessions was associated with a reduction in mean wakefulness of
almost 1 hour per night, whereas usual care (in which physicians could
Physical Activity treat insomnia as they would in normal clinical practice) had no effect on
Physical activity can improve sleep in middle-aged and older individuals in wakefulness.706 Another trial randomized 96 survivors (68% breast cancer;
non-cancer settings.1206-1208 Physical activity may also improve sleep in 87% female) to a 7-week intervention of CBT, armodafinil, CBT plus
patients with cancer and survivors.210,1209-1214 One randomized controlled armodafinil, or placebo.1222 CBT resulted in significant improvements in
trial compared a standardized yoga intervention plus standard care with insomnia symptoms and sleep quality at 0 and 3 months after the
standard care alone in 410 survivors (75% breast cancer; 96% women) intervention, but armodafinil had no effect. A recent meta-analysis
with moderate to severe sleep disruption.1211 Participants in the yoga arm identified 8 studies, including 752 cancer survivors, and found large effect
experienced greater improvements in global and subjective sleep quality, sizes for self-reported insomnia severity (d = .77) following CBT.1223
daytime functioning, and sleep efficiency (all P ≤ .05). In addition, the use Further, a meta-analysis of randomized controlled trials in cancer survivors
of sleep medication declined in the intervention arm (P ≤ .05). However, a found strong evidence that CBT-I can produce large and durable effects
2013 systematic review concluded that the evidence that yoga programs on insomnia severity.1223 In fact, the American College of Physicians
aimed at cancer survivors improve insomnia or sleep quality is very
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recommends that CBT be the initial treatment for all adults with chronic In addition, antidepressants, antihistamines, atypical antipsychotics, other
insomnia disorder.1217 BZD receptor agonists, and nutritional/herbal supplements (eg, melatonin)
are often used off-label for the treatment of insomnia, even though limited
A small randomized controlled trial of 57 survivors (54% breast cancer; to no efficacy or effectiveness data are available for this use. The panel
75% women) found that mind–body interventions (mindfulness meditation noted that these medications are associated with significant risks and
or mind-body bridging) decreased sleep disturbance more than sleep should be used with caution. One small, open-label study found that the
hygiene education did.1224 A preliminary report of a subset of participants in antidepressant mirtazapine increased the total amount of nighttime sleep
a larger randomized controlled trial of breast cancer survivors showed that in patients with cancer.1230 A recent randomized, double-blind, placebo-
MBSR improved objective sleep parameters, including sleep efficiency controlled study of 95 postmenopausal breast cancer survivors found that
and percent of sleep time.1225 melatonin subjectively improved sleep quality after 4 months of treatment
(mean change in Pittsburgh Sleep Quality Index [PSQI] score, -0.1 for
A randomized, partially blinded, noninferiority trial compared CBT with
placebo and -1.9 for melatonin; P < .001).845 Overall, however, data on
MBSR in 111 patients with cancer.1226 Both groups experienced
pharmacologic interventions aimed at improving sleep in patients with
improvements in sleep diary-measured sleep onset latency, wake after
cancer and survivors are lacking.1183
sleep onset, total sleep time, stress, and mood disturbance. MBSR was
inferior to CBT for improving insomnia severity immediately following the Treatment of Obstructive Sleep Apnea
intervention, but was noninferior at 5 months. These results have not been
Weight loss should be recommended to survivors with OSA, because
replicated in survivors, and the relative efficacy of these strategies is not studies have shown weight loss to be associated with reduced hypoxia
established in this population. Another randomized study compared Tai and excessive sleepiness in patients with OSA.1231 Small randomized
Chi Chih, a mindful movement meditation, with CBT-I in 90 breast cancer
studies have also shown that physical activity can improve OSA symptoms
survivors and found it to be non-inferior for improving insomnia symptoms independent of weight loss.1232,1233 In addition, survivors with OSA should
at 3, 6, and 15 months after the intervention.1227
be referred to a sleep specialist or PCP. The most common medical
treatment for OSA is continuous positive airway pressure (CPAP).1234
Pharmacologic Interventions
Many pharmacologic treatments for sleep disturbances are available, Treatment of Restless Legs Syndrome
including hypnotics for insomnia (eg, zolpidem, ramelteon).1228,1229 Many of
For RLS associated with iron deficiency, iron replacement can improve
the FDA-approved hypnotics are BZD receptor agonists and can be
symptoms. In addition, preferred first-line treatments for RLS are
associated with dependence, abuse, and withdrawal. The panel therefore dopamine agonists, gabapentin, and enacarbil.1235-1243 Two separate recent
recommends that survivors taking these medications be assessed every 1
meta-analyses found dopamine agonists and calcium channel alpha-2-
to 3 months to determine if they are still needed. In addition, survivors
delta ligands (eg, gabapentin) to be helpful for reducing RLS symptoms
should be informed that hypnotic medications may cause complex sleep- and improving sleep in the non-cancer setting.1243,1244
related behaviors (eg, sleep driving, sleep eating).
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Survivorship
Additional treatment options include opioids, clonazepam, and sleep

hygiene education. Referral to a sleep specialist or PCP is also an
appropriate option for survivors with RLS. In addition, certain mind-body
interventions and dietary supplementation may benefit some patients with
RLS, although data are limited.1245 The American Academy of Neurology
also has clinical practice guidelines for the treatment of adults with
RLS.1246
Summary
With improved diagnostic and treatment modalities, the population of
cancer survivors is rapidly growing. Many survivors will experience late
and/or long-term effects of cancer and its treatment that can include
physical and/or psychosocial problems. These issues need to be
addressed in a regular and systematic manner. Unfortunately, many of
these effects are not addressed until discharge from the oncologist, and
interventions may be left to health care providers who may not have much
experience treating the concerns of cancer survivors. The NCCN
Survivorship Panel hopes that these guidelines can help both oncologic
and primary health care professionals lessen the burden left on survivors
by their cancer experience so they can transition back to a rewarding life.
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Survivorship
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NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)

NCCN Guidelines Version 2.2020 NCCN Guidelines Index

Kristin Dickinson, PhD, RN § at the University of Utah *William Pirl, MD q NCCN

Debra L. Friedman, MD, MS € ‡ † Center/University Hospitals Seidman *M. Alma Rodriguez, MD ‡ † Þ

NCCN Guidelines Version 2.2020 NCCN Guidelines Index

NCCN Guidelines Version 2.2020 NCCN Guidelines Index

ɛ Epidemiology q Psychiatry, psychology,

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ξ Bone marrow transplantation # Nursing

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Healthy Lifestyles Halle C. F. Moore, MD †

Continue ɛ Epidemiology € Pediatric oncology

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SURV-A Survivorship Assessment (Patient Version)

SURV-B Survivorship Resources for Health Care Professionals and Patients

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SPA-A Guidance for Resistance Training Recommendations

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SCARDO-2 Anxiety, Depression, Trauma, and Distress

NCCN Guidelines Version 2.2020 NCCN Guidelines Index

LATE EFFECTS/LONG-TERM PSYCHOSOCIAL AND PHYSICAL PROBLEMS

NCCN Guidelines Version 2.2020 NCCN Guidelines Index

LATE EFFECTS/LONG-TERM PSYCHOSOCIAL AND PHYSICAL PROBLEMS

SPAIN-10 Post-radiation Pain

NCCN Guidelines Version 2.2020 NCCN Guidelines Index

NCCN Guidelines Version 2.2020 NCCN Guidelines Index

NCCN Guidelines Version 2.2020 NCCN Guidelines Index

GENERAL PRINCIPLES OF THE SURVIVORSHIP GUIDELINES

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 2.2020 NCCN Guidelines Index

SCREENING FOR SUBSEQUENT NEW PRIMARY CANCERS

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 2.2020 NCCN Guidelines Index

ASSESSMENT BY HEALTH CARE PROVIDER (ONCOLOGY OR PRIMARY CARE) AT REGULAR INTERVALS

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 2.2020 NCCN Guidelines Index

SURVIVORSHIP ASSESSMENT (Patient Version)

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 2.2020 NCCN Guidelines Index

Cardiac Toxicity Questions 1–2 If YES to any question, refer to SCARDIO-1

Cognitive Function Questions 6–8 If YES to any question, refer to SCF-1

Fatigue Questions 9–11 If YES to either question 9 or 10,

Lymphedema Questions 12 If YES to question 12, refer to SLYMPH-1

Hormone-Related Symptoms Questions 13–14 If YES to any question, refer to SMP-1

Pain Questions 15–16 If YES to question 15

Sexual Function Questions 17–18 If YES to any question, refer to SSF-1

Sleep Disorder Questions 19–21 If YES to any question, refer to SSD-1

Healthy Lifestyle Questions 22–25 If NO to question 22 or 23, or YES to question 24, OR if

Immunizations and Infections Questions 26–27 If NO to question 26,

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 2.2020 NCCN Guidelines Index

SURVIVORSHIP RESOURCES FOR HEALTH CARE PROFESSIONALS AND PATIENTSa

NCCN Guidelines Version 2.2020 NCCN Guidelines Index

SURVIVORSHIP RESOURCES FOR HEALTH CARE PROFESSIONALS AND PATIENTSa

NCCN Guidelines Version 2.2020 NCCN Guidelines Index