Authors: Kerry S. Courneya, Ph.D., Janette L. Vardy, M.D., Ph.D., Christopher J. O’Callaghan, D.V.M., Ph.D., Sharlene Gill, M.D., Christine M. Friedenreich, Ph.D., Rebecca K.S. Wong, M.B., Ch.B., Haryana M. Dhillon, Ph.D., +20 , Victoria Coyle, M.B., B.Ch., Ph.D., Neil S. Chua, M.D., Derek J. Jonker, M.D., Philip J. Beale, Ph.D., Kamal Haider, M.D., Patricia A. Tang, M.D., Tony Bonaventura, M.D., Ralph Wong, M.D., Howard J. Lim, M.D., Ph.D., Matthew E. Burge, M.B., B.S., Stacey Hubay, M.D., Michael Sanatani, M.D., Kristin L. Campbell, Ph.D., Fernanda Z. Arthuso, Ph.D., Jane Turner, M.Phil., Ralph M. Meyer, M.D., Michael Brundage, M.D., Patti O’Brien, M.Sc., Dongsheng Tu, Ph.D, and Christopher M. Booth, M.D., for the CHALLENGE Investigators*
Published June 1, 2025
N Engl J Med 2025;393:13-25
DOI: 10.1056/NEJMoa2502760
Abstract
Background
Preclinical and observational studies suggest that exercise may improve cancer outcomes. However, definitive level 1 evidence is lacking.
Methods
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.
Results
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).
Conclusions
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.)
Notes
This article was published on June 1, 2025, at NEJM.org.
A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.
Supported by the Canadian Cancer Society, the Australian National Health and Medical Research Council, and Cancer Research UK.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.