Guest Editor’s Note: Several studies have shown that regular physical activity helps to reduce the symptom burden and improve disease-related outcomes in patients with cancer. In this article, Jessica M. Scott, PhD, and Neil M. Iyengar, MD, summarize the current evidence surrounding exercise therapy and its impact across the cancer care continuum; they also highlight the need for robust confirmatory data.
Jessica M. Scott, PhD
Neil M. Iyengar, MD
National agencies (eg, American College of Sports Medicine,1 American Cancer Society2) recommend avoidance of inactivity and adherence to regular exercise training consistent with national guidelines for healthy adults3 across the cancer continuum. Here we briefly outline the evidence supporting exercise training for management of symptom burden (eg, poor health-related quality of life, fatigue) and tumor-related outcomes (eg, tumor biology, recurrence, cancer-specific mortality) across the cancer continuum beginning with the diagnosis of primary disease, continuing with adjuvant therapy and surveillance after treatment, and finally during distant disease recurrence (metastasis).
In the presurgical setting, a primary question of interest is whether short-term (about 4–6 weeks) exercise training can augment cardiovascular (physiologic) function (eg, cardiorespiratory fitness) and thus improve patient-reported outcomes and reduce postoperative complications. In a meta-analysis of the effects of preoperative exercise training in patients with lung cancer, Garcia et al4 reported that in comparison to usual care, exercise training decreased hospital stay by almost 5 days and reduced the risk of postoperative complications by 55%.
The presurgical stage has also emerged as a setting to evaluate both biological and clinical endpoints in response to short-term exercise training.5-7 For instance, in a randomized controlled trial, Jones et al8,9 explored the safety and efficacy of exercise training in combination with neoadjuvant chemotherapy compared with chemotherapy alone in 20 patients with previously untreated breast cancer. Exercise training improved several host-related circulating factors (ie, circulating endothelial progenitor cells, proinflammatory cytokines). Collectively, extant evidence indicates that presurgical exercise training is an effective intervention to reduce postoperative complications and may improve biological factors associated with tumor control.
Several randomized controlled trials have assessed the efficacy of exercise training on various patient-reported outcomes in this setting. In a meta-analysis of 32 studies in women undergoing adjuvant therapy for breast cancer, Furmaniak et al10 found that exercise training reduced fatigue. Similar findings were reported in a meta-analysis of 15 studies in men undergoing androgen-deprivation therapy for prostate cancer.11In yet another meta-analysis of randomized controlled trials evaluating the effects of exercise training on cardiorespiratory fitness in patients with adult-onset cancer, Scott et al12 found that among 14 studies conducted during therapy, exercise training improved cardiorespiratory fitness compared with usual care.
Data from prospective trials evaluating the efficacy of exercise training on the rates of disease recurrence are currently not available. However, an unplanned, retrospective analysis of a randomized controlled trial examined the efficacy of aerobic or resistance training on patient-reported outcomes in patients receiving standard chemotherapy for operable breast cancer. Courneya et al13 reported a nonsignificant higher 8-year disease-free survival rate (83%) in the two exercise training groups relative to the group given usual care (76%). Findings to date indicate that exercise training during therapy may mitigate declines in both physiologic and patient-reported outcomes. Additional work is needed to determine the effects of exercise training during therapy on disease recurrence.
In a meta-analysis of 10 studies (n = 15,450 adult survivors of childhood cancer) examining the association between exercise training after treatment and all-cause mortality, exercise training was associated with a 42% and 48% reduced risk of total mortality for colorectal and breast cancers, respectively.14 Exercise training was also associated with a 19%, 39%, and 11% reduction in all-cause, recurrence/disease progression, and health-related deaths.15 In another meta-analysis evaluating the effects of exercise training on cardiorespiratory fitness, among 27 randomized controlled trials conducted after therapy, exercise training was associated with a significant increase in cardiorespiratory fitness compared with usual care.12
In addition to conferring physiologic benefits, exercise training may also improve patient-reported outcomes. For instance, Mishra et al16 reported that among 30 randomized controlled trials involving cancer survivors, exercise training improved global quality of life relative to non–exercise training controls. Data from prospective randomized trials on the effects of exercise training on tumor control are currently not available. However, an unplanned, retrospective analysis of a randomized controlled trial in patients with lymphoma17 found no difference in the 5-year progression-free survival rate between patients allocated to 12 weeks of supervised exercise training compared with a non–exercise training control group.18 The Colon Health and Life-Long Exercise Change (CHALLENGE) trial is an ongoing multicenter phase III trial investigating the effects of structured exercise training on recurrence and cancer-specific mortality in patients with stage III colorectal cancer.19 In summary, the majority of studies support the conclusion that exercise training after therapy may improve physiologic and patient-reported outcomes and may reduce the risk of late events.
Jun J. Mao, MD, MSCE
Advanced (Metastatic) Disease
The high disease and treatment-related burden for patients with metastatic disease may alter exercise training tolerability, safety, and response.20 A systematic review of 21 studies reported that structured exercise training is a feasible intervention that maintains or improves measures of cardiorespiratory fitness and select patient-reported outcomes, although considerable heterogeneity in study methodology and quality hampered data interpretation.21
Additionally, two recent trials reported no significant differences in cardiorespiratory fitness or quality of life following exercise training among patients receiving therapy for metastatic breast cancer.22,23 However, the acceptable tolerability and benefit of exercise training in a subset of patients receiving endocrine-based therapy warrant further evaluation and are currently being assessed in a phase I study (ClinicalTrials.gov identifier NCT03988595).
In totality, meta-analyses and systematic reviews conclude that exercise training improves patient-reported outcomes and physical functioning in a broad array of patients with cancer before, during, and after treatment.1,2,24 In addition to having beneficial effects on symptomatology, emerging data suggest that exercise training during these phases may lower the risk of death from cancer, although confirmatory data from adequately powered randomized trials are not yet available.
DISCLOSURE: Dr. Scott reported no conflicts of interest. Dr. Iyengar has served as a consultant to Novartis and Puma Biotechnology.
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