Clinical question: Does a three-year structured exercise program, started after adjuvant chemotherapy, improve disease-free and overall survival in patients with resected colon cancer compared to health-education materials alone?
Background: Colorectal cancer is a leading cause of cancer-related mortality. Despite standard management with surgery and adjuvant chemotherapy, recurrence rates remain high, and survivors often experience reduced quality of life and physical functioning. Observational and preclinical studies have suggested that exercise may improve cancer outcomes, but definitive randomized evidence has been lacking.
Study design: Phase 3, multicenter, randomized controlled trial (the CHALLENGE trial) comparing a three-year structured exercise program to health-education materials alone in patients with resected colon cancer who had completed adjuvant chemotherapy.
Setting: The trial was conducted at 55 centers,
Synopsis: The study enrolled patients two to six months after completion of adjuvant chemotherapy for colon cancer, with a median follow-up of 7.9 years. The primary endpoint was disease-free survival; secondary endpoints included overall survival and measures of physical functioning. A total of 889 patients were randomized to either the structured exercise group (445 patients) or the health-education group (444 patients). The exercise intervention led to a statistically significant improvement in disease-free survival (HR for recurrence, new primary cancer, or death, 0.72; 95% CI, 0.55–0.94; P=0.02) and findings consistent with improved overall survival (HR for death, 0.63; 95% CI, 0.43–0.94). The five-year disease-free survival rate was 80.3% in the exercise group versus 73.9% in the control group (difference, 6.4 percentage points; 95% CI, 0.6 to 12.2). The eight-year overall survival rate 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 were more common in the exercise group (18.5% versus 11.5%) but were manageable.
Bottom line: A three-year structured exercise program initiated soon after adjuvant chemotherapy for colon cancer significantly improves disease-free survival and is associated with findings consistent with improved overall survival, with a favorable benefit-to-harm ratio. These results support the incorporation of structured exercise into standard post-treatment care for colon cancer survivors.
Citation: Courneya KS, et al. Structured Exercise after Adjuvant Chemotherapy for Colon Cancer. N Engl J Med. 2025;393(1):13-25. doi:10.1056/NEJMoa2502760.
Dr. Vura is an academic hospitalist in the division of hospital medicine at UT Health San Antonio and a clinical assistant professor in the department of internal medicine at the Joe R. & Teresa Long School of Medicine.