1. In this randomized controlled trial, patients with resected stage III or high-risk stage II colon cancer who completed adjuvant chemotherapy experienced significantly longer disease-free survival with a three-year structured exercise intervention.
2. The structured exercise intervention was associated with longer overall survival and improvements in exercise metrics, including VO₂ max and 6-minute walk distance.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Current management of stage III and high-risk stage II colon cancer typically involves surgery followed by adjuvant chemotherapy. While these treatments are standard of care, they are associated with significant impacts on quality of life, and recurrence rates remain a challenge. Observational and preclinical studies have suggested a potential survival benefit of exercise in patients with colorectal cancer. This trial, conducted by the Canadian Cancer Trials Group, assessed the efficacy of a three-year structured exercise program in patients with colorectal cancer who had completed adjuvant chemotherapy. Participants were randomized into two groups: a health education group and an exercise group. Participants in the exercise group showed greater improvements in several physical performance measures, including predicted maximum oxygen consumption and 6-minute walk distance. Changes in waist circumference and body weight were minimal between groups. Importantly, the exercise group experienced extended overall survival and significantly longer disease-free survival. They also reported greater improvements in physical function from baseline compared to the health education group. However, musculoskeletal adverse events were more frequently reported in the exercise group. Limitations of the study included slow participant recruitment, failure to reach the targeted number of events, potential confounding from increased social contact in the exercise group, and the lack of stratification for Lynch syndrome. Overall, this study provides evidence that a structured exercise program may improve disease-free and overall survival in patients with colon cancer following adjuvant chemotherapy.
Click here to read the study in NEJM
In-Depth [randomized controlled trial]: This randomized controlled trial evaluated the efficacy of a three-year structured exercise program in patients with resected colon cancer. Eligible participants had resected stage III or high-risk stage II colon adenocarcinoma and had completed adjuvant chemotherapy within 2 to 6 months before enrollment. Additional inclusion criteria included an Eastern Cooperative Oncology Group (ECOG) performance status score of 0–1 (indicating no or minimal disability), participation in less than 150 minutes of moderate-to-vigorous exercise per week, and the ability to complete a 6-minute walk test. The primary outcome was disease-free survival, defined as the time from randomization to any of the following events: cancer recurrence, development of a second primary cancer, new primary colorectal cancer, or death. The annual incidence of such events was significantly lower in the exercise group (3.7%; 95% Confidence Interval [CI], 3.0–4.5) compared to the health-education group (5.4%; 95% CI, 4.5–6.4), yielding a hazard ratio (HR) of 0.72 (95% CI, 0.55–0.94; p=0.02). Subgroup analyses showed consistent benefit, with all hazard ratios ≤ 0.87. The annual incidence of death was also lower in the exercise group (1.4%; 95% CI, 1.0–1.8) compared to the health-education group (2.3%; 95% CI, 1.7–2.8), with an HR for death of 0.63 (95% CI, 0.43–0.94). Again, this trend was consistent across all prespecified subgroups, with hazard ratios ≤ 0.84. Self-reported physical functioning assessed using the 36-Item Short Form Health Survey showed consistently greater improvement in the exercise group at all time points: 6 months (7.1 vs. 1.3), 1 year (6.8 vs. 3.3), 18 months (7.2 vs. 2.4), 2 years (6.1 vs. 2.6), and 3 years (6.1 vs. 3.0). Regarding safety, 82% of participants in the exercise group and 76.4% in the health-education group reported at least one adverse event. Musculoskeletal adverse events were more common in the exercise group (18.5%) compared to the health-education group (11.5%). In summary, this study demonstrates that a structured exercise intervention is an effective and well-tolerated strategy to improve disease-free and overall survival in patients with resected colon cancer who have completed adjuvant chemotherapy.
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