Exercise and cancer: from fatigue to survival
Table of contents
- Why exercise entered oncology
- What the international guideline recommends
- Fatigue: the most solid effect
- During treatment: the example of breast cancer
- Survival: what observational studies show
- Colon cancer: mechanisms and what is still missing
- How to guide in practice
- How NEXO helps train this reasoning
- Frequently asked questions
- Take-home messages
- References
A man in his early sixties finishes adjuvant chemotherapy for colon cancer. He asks the oncologist whether he can start walking again and whether the effort will hinder his recovery. The answer he hears is vague: "do what you can". Three months later, he spends most of the day sitting, with a fatigue that does not improve.
The scene is common, and so is the vague answer. An analysis of more than nine thousand cancer survivors found that only 30 to 47 out of every 100 met the physical activity recommendations (Schmitz, 2019). Several studies point to the lack of a recommendation from the oncology team as one of the reasons (Schmitz, 2019).
This text shows what exercise changes in fatigue, quality of life and survival, how much to prescribe according to the international guideline and how to turn the guidance into a referral.
Key points
- The 2019 international guideline concluded that exercise is generally safe during and after cancer treatment and that every survivor should avoid inactivity (Campbell, 2019).
- There is strong evidence of benefit from exercise on anxiety, depressive symptoms, fatigue, quality of life and physical function (Campbell, 2019).
- In a meta-analysis of 113 studies, exercise reduced cancer fatigue more than the available medications (Mustian, 2017).
- In observational studies, more physical activity after diagnosis was associated with lower mortality in breast and colorectal cancers, with hazard ratios between 0.58 and 0.63 (Friedenreich, 2020).
- In breast cancer trials, it has not yet been possible to draw conclusions about recurrence or mortality (Lahart, 2018).
- The practical proposal is simple: assess, advise and refer (Schmitz, 2019).
Summary
- Why exercise entered oncology
- What the international guideline recommends
- Fatigue: the most solid effect
- During treatment: the example of breast cancer
- Survival: what observational studies show
- Colon cancer: mechanisms and what is still missing
- How to guide in practice
- How NEXO helps train this reasoning
- Frequently asked questions
- Take-home messages
Why exercise entered oncology
For a long time, the guidance for people with cancer was to rest. The change began when trials showed that exercise was safe and improved physical capacity. The 2010 American College of Sports Medicine roundtable had already concluded that cancer survivors could train safely enough to improve physical fitness, quality of life and fatigue (Campbell, 2019).
The starting point is well known. Cancer survivors often have loss of physical function and quality of life and face a higher risk of recurrence and overall mortality than people without cancer (Campbell, 2019). Exercise acts precisely on physical capacity, which treatment often reduces.
In the decade after 2010, evidence accumulated that physical activity is related to more types of cancer than previously thought and that sedentary behavior may also play a role (Patel, 2019).
In 2019, an international group reviewed the evidence accumulated since then. The conclusion that exercise and exercise tests are generally safe was maintained, as was the recommendation that every survivor avoid inactivity (Campbell, 2019). The novelty was turning the evidence into specific prescriptions for each outcome with strong evidence (Campbell, 2019).
The question changed from "can I?" to "how much, of what type and for what?". This applies both during and after treatment, and the answer depends on the outcome one wants to improve.
There is also the prevention side, which is another matter. A review for the committee of the American physical activity guidelines found strong evidence of an association between more physical activity and lower risk of bladder, breast, colon, endometrial, esophageal adenocarcinoma, kidney and stomach cancers (McTiernan, 2019). This text deals with people who have or have had cancer.
What the international guideline recommends
The 2019 guideline classified outcomes by strength of evidence (Campbell, 2019). For anxiety, depressive symptoms, fatigue, health-related quality of life and physical function, the evidence was considered strong, and the group proposed a prescription with frequency, intensity, time and type of exercise (Campbell, 2019).
For fatigue, the recommendation is moderate-intensity aerobic training three times a week for at least 12 weeks (Campbell, 2019). For anxiety and depressive symptoms, the same aerobic training for 12 weeks, or combined aerobic and strength training twice a week for 6 to 12 weeks (Campbell, 2019).
For quality of life, combined moderate-intensity aerobic and strength training, two to three times a week for at least 12 weeks, brought improvement during and after treatment (Campbell, 2019). Strength training was also considered safe in women with lymphedema or at risk of lymphedema after breast cancer (Schmitz, 2019).
The guideline also made clear what is still unknown. For fatigue, going beyond 150 minutes a week of aerobic exercise did not appear to bring the greatest reduction, and the relationship between amount and effect remains uncertain (Campbell, 2019). The studies also rarely selected people with the worst baseline values, which limits application to those who need it most (Campbell, 2019).
| Outcome | Suggested prescription | Source |
|---|---|---|
| Fatigue | Moderate aerobic three times a week for at least 12 weeks (Campbell, 2019) | International guideline (Campbell, 2019) |
| Anxiety | Moderate aerobic three times a week for 12 weeks, or combined twice a week for 6 to 12 weeks (Campbell, 2019) | International guideline (Campbell, 2019) |
| Depressive symptoms | Moderate aerobic three times a week for at least 12 weeks, or combined twice a week for 6 to 12 weeks (Campbell, 2019) | International guideline (Campbell, 2019) |
| Quality of life | Combined aerobic and strength, two to three times a week for at least 12 weeks (Campbell, 2019) | International guideline (Campbell, 2019) |
| Lymphedema after breast cancer | Strength training considered safe (Schmitz, 2019) | Review on referral (Schmitz, 2019) |
Fatigue: the most solid effect
Fatigue is the most frequent symptom of cancer and its treatment and one of the most disabling. It does not improve with rest, and prolonged rest tends to worsen the deconditioning that feeds it.
The Cochrane review by Cramp gathered 56 studies with 4068 participants, most with breast cancer (Cramp, 2012). At the end of the intervention, exercise reduced fatigue compared with control, with a standardized mean difference of 0.27 (Cramp, 2012). The authors concluded that aerobic exercise can be considered beneficial for fatigue during and after treatment, especially in solid tumors (Cramp, 2012).
The main meta-analysis of the review combined 38 comparisons, with 1461 participants in the exercise group and 1187 in the control group (Cramp, 2012). The studies included people on active treatment, in long-term follow-up and in palliative care (Cramp, 2012). Studies in which participants only received advice about the benefits of exercise, without a defined program, were excluded (Cramp, 2012).
The meta-analysis by Mustian compared the four most recommended approaches for fatigue in 113 studies with 11 525 participants (Mustian, 2017). Exercise had the largest effect, with a weighted effect size of 0.30 (Mustian, 2017). Psychological interventions had an effect of 0.27, and the combination of exercise with psychological intervention, 0.26 (Mustian, 2017). Medications had an effect of 0.09, with no significant improvement (Mustian, 2017).
The clinical message is direct. Before looking for a drug for cancer fatigue, it is worth prescribing exercise and considering psychological support (Mustian, 2017). At the same time, intense fatigue calls for investigation of treatable causes, such as anemia, hypothyroidism, fluid and electrolyte disorders and medication effects. The text on fatigue with abiraterone shows how this reasoning applies to a concrete case.
Anxiety and mood
Anxiety and depressive symptoms are also among the outcomes with strong evidence (Campbell, 2019). This does not replace mental health assessment, especially when symptoms are intense or there is risk. The text on anxiety in the patient with cancer helps separate expected anxiety from the disorder and from organic causes.
During treatment: the example of breast cancer
Breast cancer accounts for most of the trials, which allows a closer look at what happens during treatment. The Cochrane review by Furmaniak included 32 studies with 2626 women on adjuvant chemotherapy or radiotherapy (Furmaniak, 2016).
Exercise during treatment probably improves physical fitness, with a standardized mean difference of 0.42, and slightly reduces fatigue, with a difference of 0.28 (Furmaniak, 2016). The effect on overall quality of life was small or absent, and for depressive symptoms there was little or no difference (Furmaniak, 2016).
There was also a sign of improvement in cognitive function (Furmaniak, 2016). For those living with complaints of memory and concentration during chemotherapy, it is one more reason to keep the person active, without promising an effect that studies have not yet confirmed with confidence.
After treatment, the Cochrane review by Lahart gathered 63 trials with 5761 women (Lahart, 2018). Cardiorespiratory fitness improved, with a standardized mean difference of 0.44 and moderate-quality evidence (Lahart, 2018). The authors, however, stated that nothing could be concluded about breast cancer mortality, overall mortality or recurrence (Lahart, 2018).
This contrast is important. The breast trials show gains in physical fitness and symptoms, but they were not designed or sized to answer whether exercise changes survival (Lahart, 2018). For shoulder and lymphedema rehabilitation, the text on who decides the treatment sequence in breast cancer brings the team context.
Before surgery
Exercise also comes in before treatment. Prehabilitation seeks to reach surgery in better physical and nutritional condition. The text on prehabilitation in gastric cancer shows how the weeks before the operation can be used.
Survival: what observational studies show
The question patients care about most is whether exercise helps them live longer. So far, most of the answer comes from observational studies.
The meta-analysis by Friedenreich gathered 136 studies (Friedenreich, 2020). For all cancers together, higher physical activity before diagnosis was associated with lower cancer mortality, with a hazard ratio of 0.82, and activity after diagnosis, with a hazard ratio of 0.63 (Friedenreich, 2020). In breast and colorectal cancers, activity after diagnosis had a stronger association, with hazard ratios between 0.58 and 0.63 (Friedenreich, 2020).
In breast cancer, the relationship was gradual, with marked risk reductions up to 10 to 15 metabolic equivalents per hour per week (Friedenreich, 2020). This range corresponds, approximately, to a few hours of walking per week.
The review by McTiernan for the American committee reached a similar conclusion, with moderate or limited associations between more activity and lower mortality in breast, colorectal and prostate cancer (McTiernan, 2019). The ACSM report on physical activity and cancer considered it likely that activity before and after diagnosis is relevant to survival in breast and colon cancer (Patel, 2019).
The benefits appeared in most of the subgroups analyzed, including sex, body mass index, menopausal status and colorectal cancer subtypes (Friedenreich, 2020). Activity after diagnosis was associated with lower overall mortality in several tumor types, including breast, colorectal, prostate, lung, kidney, stomach and hematologic cancers (Friedenreich, 2020).
The McTiernan review summarized 45 reports with hundreds of epidemiological studies and several million participants (McTiernan, 2019). Even so, the authors themselves call for more research on survival in less-studied cancers (McTiernan, 2019).
The limits of these data
Observational studies have a known weakness: people who exercise more may have less severe disease, fewer comorbidities and more resources. Part of the association may reflect this, even with statistical adjustments. In addition, advanced disease reduces activity, which can reverse the direction of the relationship.
For this reason, definitive proof depends on randomized trials with survival outcomes. These trials are rare, long and hard to run, and results from one cancer type cannot be automatically transferred to another.
Colon cancer: mechanisms and what is still missing
Colon cancer is the setting in which the hypothesis that exercise changes recurrence has been most studied. The ACSM report describes several biologically plausible mechanisms by which physical activity may influence cancer (Patel, 2019). The same report notes that reducing sitting time may lower the risk of endometrial, colon and lung cancer (Patel, 2019).
One of the mechanisms studied is visceral fat. It is associated with a higher risk of recurrence in colon cancer survivors (Brown, 2017). In a trial with 39 stage I to III colon cancer survivors, participants were randomly assigned to control, 150 minutes per week of aerobic exercise or 300 minutes per week, for six months (Brown, 2017).
Exercise reduced visceral fat in proportion to the amount practiced (Brown, 2017). Each additional 60 minutes per week of exercise predicted a reduction of 2.7 square centimeters of visceral fat (Brown, 2017). It is an intermediate outcome, and it does not prove that recurrence falls, but it helps to understand a possible path.
Other possible mechanisms
The ACSM report describes other paths beyond visceral fat, such as changes in sex hormones and in inflammation markers (Patel, 2019). In one of the examples cited, greater exercise-induced weight loss in postmenopausal women brought a greater reduction in estradiol and C-reactive protein (Patel, 2019). These changes could reduce the risk of breast and endometrial cancer, but they remain intermediate outcomes (Patel, 2019).
Care when generalizing
The colon and breast data are the strongest, but tumors differ in biology, treatment and prognosis. A favorable result in one cancer type does not justify saying that exercise reduces recurrence in all of them. In the conversation with the patient, it is worth separating what is a demonstrated benefit, such as less fatigue and better physical fitness, from what is still an association under study.
How to guide in practice
The Schmitz review proposes a simple path for the oncology team: assess, advise and refer (Schmitz, 2019). The referral may be to exercise at home or in the community, or to outpatient assessment and rehabilitation when there are limitations (Schmitz, 2019).
Assess
Assess means asking how much the person moves and identifying what changes the safety of exercise: significant anemia, peripheral neuropathy, bone metastasis, lymphedema, cardiotoxicity and recent surgery. The international guideline provides specific safety considerations for cancer survivors (Campbell, 2019).
Advise
Advising means stating clearly that exercise is part of the treatment. In several studies, more than 80 out of every 100 patients said they wanted to receive physical activity guidance from the oncology team (Schmitz, 2019). Listening first to what the person fears and hopes for makes a difference, as the text on the patient's agenda shows. For those who are ambivalent, motivational interviewing offers a path.
Referring
Referring means choosing the destination according to complexity. Some patients can follow the guidance on their own, and others need supervised rehabilitation (Schmitz, 2019). Waiting for the ideal structure before starting to refer wastes the chance to make more patients active with the structure that already exists (Schmitz, 2019).
What gets in the way of implementation
The Schmitz review lists the obstacles on the system side: screening and referral capacity, lack of a registry of programs, reimbursement and training of professionals (Schmitz, 2019). To overcome them, care must be coordinated with the right professionals and the behaviors of clinicians, patients and program providers must change (Schmitz, 2019).
In the consultation, a few simple measures help: recording the activity level as one records a vital sign, handing over the agreed guidance in writing and bringing the subject up again at the follow-up visit. The minimum message, for those who cannot yet follow a full prescription, is to avoid inactivity (Campbell, 2019).
Excess of caution and of tests
The opposite risk also exists: ordering too many tests and clearances before allowing a walk. For most people, walking and reducing sitting time does not require a special assessment. The concept of quaternary prevention helps weigh what each test adds.
Back to the case
In the man from the opening, the conversation could start with fatigue and with what he wants to do again. The initial goal would be to reduce sitting time and walk at moderate intensity, progressing to the prescription for fatigue, of three sessions a week for at least 12 weeks (Campbell, 2019). Strength training would come next, and chemotherapy-induced neuropathy, if present, would guide the choice of exercises.
How NEXO helps train this reasoning
In NEXO, the case of the day is fictional, with a real clinical presentation and up to six progressive clues, and you propose the diagnosis by searching for the ICD-10 code.
The limits on using the game are described on the NEXO economy page. If you research the teaching of clinical reasoning, the page for researchers explains how to get in touch. Professionals who write or review cases find information on curation and on creators, and institutions can learn about the proposal on the partnerships page. For the most frequent reasons for consultation, see the most common codes in primary care.
Frequently asked questions
Is it safe to exercise during chemotherapy?
In general, yes. The international guideline concluded that exercise and exercise testing are generally safe during and after treatment, with specific considerations for each situation (Campbell, 2019).
How much exercise is recommended for fatigue?
Moderate-intensity aerobic training three times a week, for at least 12 weeks (Campbell, 2019).
Does exercise work better than medication for fatigue?
In the meta-analysis of 113 studies, exercise had an effect of 0.30 and medications of 0.09, with no significant improvement (Mustian, 2017).
Does exercise increase survival?
In observational studies, more activity after diagnosis was associated with lower mortality in breast and colorectal cancers (Friedenreich, 2020). In the breast cancer trials, it has not yet been possible to draw conclusions about mortality or recurrence (Lahart, 2018).
Can people with lymphedema do strength training?
Strength training was considered safe in women with lymphedema or at risk of lymphedema after breast cancer (Schmitz, 2019).
Does sitting make a difference?
The ACSM report points out that reducing sitting time may lower the risk of some cancers, such as endometrial, colon and lung cancer (Patel, 2019).
Who should refer the patient?
The oncology team, by assessing, advising and referring to exercise at home, in the community or in rehabilitation (Schmitz, 2019).
Does the result apply to all types of cancer?
Most trials are in breast cancer, and the associations with survival are stronger in breast and colorectal cancer (Friedenreich, 2020). Generalizing requires caution.
Take-home messages
- Exercise is part of cancer treatment, during and after it.
- The evidence is strong for fatigue, anxiety, depressive symptoms, quality of life and physical function.
- For fatigue, exercise outperforms the available medications.
- The basic prescription is moderate aerobic activity three times a week, with strength training.
- The survival data come mainly from observational studies in breast and colorectal cancer.
- Results from one type of cancer do not automatically transfer to others.
- Assess, advise and refer is the practical path for the team.
- Avoiding inactivity is the minimum recommendation for everyone.
Play the case of the day on NEXO.
References
- Campbell KL, Winters-Stone KM, Wiskemann J, et al. Exercise Guidelines for Cancer Survivors: Consensus Statement from International Multidisciplinary Roundtable. Med Sci Sports Exerc. 2019. PMID 31626055. DOI 10.1249/MSS.0000000000002116.
- Mustian KM, Alfano CM, Heckler C, et al. Comparison of Pharmaceutical, Psychological, and Exercise Treatments for Cancer-Related Fatigue: A Meta-analysis. JAMA Oncol. 2017. PMID 28253393. DOI 10.1001/jamaoncol.2016.6914.
- Patel AV, Friedenreich CM, Moore SC, et al. American College of Sports Medicine Roundtable Report on Physical Activity, Sedentary Behavior, and Cancer Prevention and Control. Med Sci Sports Exerc. 2019. PMID 31626056. DOI 10.1249/MSS.0000000000002117.
- Cramp F, Byron-Daniel J. Exercise for the management of cancer-related fatigue in adults. Cochrane Database Syst Rev. 2012. PMID 23152233. DOI 10.1002/14651858.CD006145.pub3.
- Friedenreich CM, Stone CR, Cheung WY, et al. Physical Activity and Mortality in Cancer Survivors: A Systematic Review and Meta-Analysis. JNCI Cancer Spectr. 2020. PMID 32337494. DOI 10.1093/jncics/pkz080.
- McTiernan A, Friedenreich CM, Katzmarzyk PT, et al. Physical Activity in Cancer Prevention and Survival: A Systematic Review. Med Sci Sports Exerc. 2019. PMID 31095082. DOI 10.1249/MSS.0000000000001937.
- Furmaniak AC, Menig M, Markes MH. Exercise for women receiving adjuvant therapy for breast cancer. Cochrane Database Syst Rev. 2016. PMID 27650122. DOI 10.1002/14651858.CD005001.pub3.
- Lahart IM, Metsios GS, Nevill AM, et al. Physical activity for women with breast cancer after adjuvant therapy. Cochrane Database Syst Rev. 2018. PMID 29376559. DOI 10.1002/14651858.CD011292.pub2.
- Schmitz KH, Campbell AM, Stuiver MM, et al. Exercise is medicine in oncology: Engaging clinicians to help patients move through cancer. CA Cancer J Clin. 2019. PMID 31617590. DOI 10.3322/caac.21579.
- Brown JC, Zemel BS, Troxel AB, et al. Dose-response effects of aerobic exercise on body composition among colon cancer survivors: a randomised controlled trial. Br J Cancer. 2017. PMID 28934762. DOI 10.1038/bjc.2017.339.