Preclinical and observational studies suggest that exercise may improve cancer outcomes. However, definitive level 1 evidence is lacking.

In this phase 3, randomized trial conducted at 55 centers, we assigned patients with resected colon cancer who had completed adjuvant chemotherapy to participate in a structured exercise program (exercise group) or to receive health-education materials alone (health-education group) over a 3-year period. The primary end point was disease-free survival.

From 2009 through 2024, a total of 889 patients underwent randomization to the exercise group (445 patients) or the health-education group (444 patients). At a median follow-up of 7.9 years, disease-free survival was significantly longer in the exercise group than in the health-education group (hazard ratio for disease recurrence, new primary cancer, or death, 0.72; 95% confidence interval [CI], 0.55 to 0.94; P = 0.02). The 5-year disease-free survival was 80.3% in the exercise group and 73.9% in the health-education group (difference, 6.4 percentage points; 95% CI, 0.6 to 12.2). Results support longer overall survival in the exercise group than in the health-education group (hazard ratio for death, 0.63; 95% CI, 0.43 to 0.94). The 8-year overall survival was 90.3% in the exercise group and 83.2% in the health-education group (difference, 7.1 percentage points; 95% CI, 1.8 to 12.3). Musculoskeletal adverse events occurred more often in the exercise group than in the health-education group (in 18.5% vs. 11.5% of patients).

A 3-year structured exercise program initiated soon after adjuvant chemotherapy for colon cancer resulted in significantly longer disease-free survival and findings consistent with longer overall survival. (Funded by the Canadian Cancer Society and others; CHALLENGE ClinicalTrials.gov number, NCT00819208.).