Evidence Supports Value of Physical Activity in Patients With Cancer

Physical activity and physical function are important components of comprehensive care for patients with cancer. Physical inactivity increases the risk of cancer and other chronic health conditions.¹ The United States Department of Health and Human Services has therefore published guidelines on physical activity to mitigate this risk, recommending a cumulative total of 150 to 300 minutes of moderate-intensity physical activity per week.² Among those with a sedentary lifestyle, benefit can be seen with even small changes in physical activity. These recommendations are echoed by national guidelines for patients who have cancer and who are receiving cancer-directed therapy, as participation in routine physical activity can improve survival and patient-reported outcomes.^3,4

Baseline physical activity and physical function prior to a cancer diagnosis or treatment affects survival, with evidence spanning across solid tumor types and hematologic malignancies. For example, in a national survey of more than 7000 participants, the effect of physical activity in men with prostate cancer was evaluated.⁵ Men with a higher level of activity were more likely to be diagnosed with a low-risk tumor, however, this subgroup was also noted to be more likely to have a history of prostatespecific antigen testing. Overall, the benefit of increased physical activity, particularly walking, was associated with a lower risk of prostate cancer–specific mortality. Likewise, in a phase 3 study evaluating therapies in metastatic colorectal cancer, although no association between vigorous activity and survival was demonstrated, a higher overall survival (OS; 0-0.9 hours/week vs ≥5.0; HR, 0.80; P = .03) and progression-free survival (HR, 0.78; P = .10) were seen in those who performed at least 5 hours of nonvigorous activity per week. This study also supports the role of physical activity in lessening chemotherapyrelated toxicity such as neutropenia (HR, 0.78; P = .04), dehydration (HR, 0.10; P = .002), anorexia (HR, 0.25; P = .03), and fatigue (HR, 0.60; P = .02).⁶

Similar results have been found in patients with blood disorders. In a database study evaluating the role of physical activity in patients with lymphoma, only 46% of patients with lymphoma met the above physical activity recommendations prior to treatment, and these patients experienced significantly higher OS (HR, 0.82; P = .004).⁷ Finally, physical function is an alternative method to evaluate physical health and has also been shown to be predictive of survival of those with cancer, particularly in older adults. In a single-institution study of older adults (≥60 years) receiving intensive induction chemotherapy for acute myeloid leukemia, patients with poor physical function before the start of induction had poorer OS (6 vs 16 months; P = .018).⁸

Resilience, an individual’s ability to return to baseline function, is a growing area of research in oncology. Evidence suggests that patients with resilience have improved cancer-related survival. A higher rate of postdiagnosis physical activity in men with prostate cancer has been associated with lower prostate cancer–specific mortality.⁵ Among patients with lymphoma, those who met guidelines for physical activity at 3 years after diagnosis had significantly better OS (HR, 0.64; P = .006).⁷ This effect of physical activity on OS held true when controlled for disease aggressiveness, comorbidities, and age.

In older adults, resilience may be influenced by underlying medical conditions or physiologic aging. For example, in older adults (≥60 years) receiving inpatient induction chemotherapy for acute myeloid leukemia, a significant decline in physical function was seen in more than 80% of patients at approximately 2 months after discharge.⁹ In a study evaluating adjuvant chemotherapy regimens in older women (≥65 years) with breast cancer, nearly 50% of patients were found to be resilient with no decline in physical function.¹⁰ Forty-two percent of women had a decline in function, and of these, 47% recovered to near-baseline physical function. Thirty percent of particpants had a decline in physical function at 12 months after chemotherapy initiation. Although promising, these results may represent a more fit population of older adults with cancer, with fewer comorbidities, and higher physical function.

With evidence supporting the role of physical activity and physical function on outcomes of patients with cancer, formal interventions to improve adherence rates of these interventions have been evaluated. In patients with localized breast cancer receiving adjuvant chemotherapy, an exercise intervention of approximately 11 months showed an improvement in patient-reported physical function and quality of life (QOL) from treatment to the completion of the intervention.¹¹

Of note, there was a compliance rate of 50% to 60%, which is a limiting factor for many exercise interventions. A shorter exercise intervention of 24 weeks in patients with various cancer types and stages receiving chemotherapy had an adherence rate of approximately 70% and showed an improvement in patient-reported physical function and QOL.¹²

In hematologic malignancies, multiple studies have investigated the impact of various exercise interventions.¹³ These studies have consistently shown improvement in QOL, physical function, and depression with exercise interventions. Adherence to exercise interventions is a barrier to implemention, and various strategies have been studied to address this limitation, including tailored exercise programs, exercise routines for the patient and their caregiver, and incorporating technology into the exercise intervention.^14-16 These studies have demonstrated improved adherence rates and show that the optimal methods of helping patients effectively engage in exercise to improve physical function and QOL are continuously evolving.

The importance of physical activity and physical function is well known in the general population. In patients with cancer, these variables have been shown to have a significant association with patient-reported outcomes and survival. Exercise interventions demonstrate improvements in physical function and QOL, which may also affect an individual’s ability to tolerate therapy and alter their treatment course. It is important to encourage patients undergoing active cancer therapy to engage in physical activity and provide support to enable patients where needed.

References:

1. Ryan A, Murphy C, Boland F, Galvin R, Smith SM. What is the impact of physical activity and physical function on the development of multimorbidity in older adults over time? A population-based cohort study. J Gerontol A Biol Sci Med Sci. 2018;73(11):1538‐1544. doi:10.1093/gerona/glx251
2. 2018 Physical Activity Guidelines Advisory Committee Scientific Report. 2018 Physical Activity Guidelines Advisory Committee. US Department of Health and Human Services, 2018. February 2018. Accessed April 11, 2020. https://health.gov/sites/default/ files/2019-09/PAG_Advisory_Committee_Report.pdf
3. Exercising during cancer treatment. National Comprehensive Cancer Network. Accessed April 11, 2020. bit.ly/36UH1Pq
4. Physical activity and the cancer patient. American Cancer Society. Updated March 24, 2014. Accessed April 11, 2020. bit.ly/2MmOihx
5. Wang Y, Jacobs EJ, Gapstur SM, et al. Recreational physical activity in relation to prostate cancer-specific mortality among men with nonmetastatic prostate cancer. Eur Urol. 2017;72(6):931- 939. doi:10.1016/j.eururo.2017.06.037
6. Guercio BJ, Zhang S, Ou FS, et al. Associations of physical activity with survival and progression in metastatic colorectal cancer: results from Cancer and Leukemia Group B (Alliance)/SWOG 80405. J Clin Oncol. 2019;37(29):2620-2631. doi:10.1200/JCO.19.01019
7. Pophali PA, Ip A, Larson MC, et al. The association of physical activity before and after lymphoma diagnosis with survival outcomes. Am J Hematol. 2018;93:1543-1550.
8. Klepin HD, Geiger AM, Tooze JA, et al. Geriatric assessment predicts survival for older adults receiving induction chemotherapy for acute myelogenous leukemia. Blood. 2013;121(21):4287-4294. doi:10.1182/blood-2012-12-471680
9. Klepin HD, Tooze JA, Pardee TS, et al. Effect of intensive chemotherapy on physical, cognitive, and emotional health of older adults with acute myeloid leukemia. J Am Geriatr Soc. 2016;64(10):1988-1995. doi:10.1111/jgs.14301
10. Hurria A, Soto-Perez-de-Celis E, Allred JB, et al. Functional decline and resilience in older women receiving adjuvant chemotherapy for breast cancer. J Am Geriatr Soc. 2019;67(5):920-927. doi:10.1111/jgs.15493
11. Kirkham AA, Bland KA, Wollmann H, et al. Maintenance of fitness and quality-of-life benefits from supervised exercise offered as suportive care for breast cancer. J Natl Compr Canc Netw. 2019;17(6):695-702. doi:10.6004/jnccn.2018.7276
12. Adamsen L, Quist M, Andersen C, et al. Effect of a multimodal high intensity exercise intervention in cancer patients undergoing chemotherapy: randomised controlled trial. BMJ. 2009;339:b3410. doi:10.1136/bmj.b3410
13. Bergenthal N, Will A, Streckmann F, et al. Aerobic physical exercise for adult patients with haematological malignancies. Cochrane Database Syst Rev. 2014;(11):CD009075. doi:10.1002/14651858.CD009075.pub2
14. Schaffer K, Panneerselvam N, Loh KP, et al. Systematic review of randomized controlled trials of exercise interventions using digital activity trackers in patients with cancer. J Natl Compr Canc Netw. 2019;17(1):57-63. doi:10.6004/jnccn.2018.7082
15. Kleckner IR, Kamen C, Gewandter JS, et al. Effects of exercise during chemotherapy on chemotherapy-induced peripheral neuropathy: a multicenter, randomized controlled trial. Supportive Care Cancer. 2018;26(4):1019-1028. doi:10.1007/s00520-017-4013-0
16. Northouse LL, Mood DW, Schafenacker A, et al. Randomized clinical trial of a brief and extensive dyadic intervention for advanced cancer patients and their family caregivers. Psycho-Oncology. 2013;22(3):555-563. doi:10.1002/pon.3036