A 3-year structured exercise program initiated soon after completion of adjuvant chemotherapy improved disease-free survival and overall survival, as well as patient-reported physical functioning and health-related fitness, in patients with stage III or high-risk stage II colon cancer. These findings from the phase III CHALLENGE trial, conducted by Christopher M. Booth, MD, Director of the Division of Cancer Care and Epidemiology at Queen’s Cancer Research Institute, Kingston, Ontario, Canada, and colleagues, were presented at an onsite press briefing at the 2025 ASCO Annual Meeting.¹

“Health systems should incorporate structured exercise programs as standard of care for this patient population [those with stage III or high-risk stage II colon cancer].”

— Christopher M. Booth, MD

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According to the World Health Organization, colorectal cancer is the third most common cancer worldwide, accounting for about 10% of all cancers, and is the second leading cause of cancer-related deaths globally.² This year, it is estimated that 154,270 new cases of colorectal cancer will be diagnosed in the United States alone and that nearly 53,000 individuals will die of the disease.³

Study Methodology

The aim of this study was to test the hypothesis that a meaningful increase in recreational physical activity after adjuvant therapy is achievable and may improve disease-free survival in patients with stage III or high-risk stage II colon cancer. The researchers enrolled 889 patients with resected stage III or high-risk stage II colon cancer from 55 sites in 6 countries between 2009 and 2024. The patients who had received adjuvant chemotherapy were randomly assigned to a structured exercise program arm (n = 445) or a health education materials arm (n = 444).

The health education materials contained information promoting physical activity and healthy nutrition in addition to standard surveillance. Participants in the structured exercise program worked with a physical activity consultant who delivered an exercise intervention using behavior-change methodology over 3 years. The goal of the structured exercise program was to increase recreational physical activity by at least 10 metabolic equivalent of task hours per week from baseline during the first 6 months and to sustain that level for 3 years. (A metabolic equivalent of task is a ratio of an individual’s working metabolic rate relative to his or her resting metabolic rate.) Participants chose the type, frequency, intensity, and duration of aerobic exercise in the program.

The primary endpoint of the study was disease-free survival compared by a stratified log-rank test performed on an intention-to-treat basis. Secondary endpoints included overall survival and patient-reported outcomes (Short Form [SF]-36 physical function scale was the primary patient-reported outcome).

In the study, 51% of the participants were female. The median patient age was 61, and 90% had stage III disease.

Key Results

The researchers found that compared with health education materials, a structured exercise program resulted in statistically significant improvements in recreational physical activity, predicted VO₂ max (maximum rate of oxygen consumption attainable during physical exertion), and 6-minute walk distance—all maintained over the 3-year intervention period. With a median follow-up of 7.9 years, the study reported 224 disease-free events (93 patients in the exercise arm and 131 patients in the education arm) and 107 deaths (41 patients in the exercise arm and 66 patients in education arm).

The 5-year disease-free survival was 80% in the exercise arm and 74% in education arm (hazard ratio [HR] = 0.72; 95% confidence interval [CI] = 0.55–0.94; P = .017). The 8-year overall survival rates were 90% in the exercise arm and 83% in education arm (HR = 0.63; 95% CI = 0.43–0.94; P = .022).

The study results also showed that SF-36 physical function was substantially improved in the patients in the exercise arm at 6 months (mean change scores, 7.42 vs 1.10, P < .001). And this improvement was sustained for 24 months.

In the safety analysis, 19% of patients in the exercise arm reported any grade of musculoskeletal adverse event over the course of the study, compared with 12% of patients in the education arm. A total of 10% of the musculoskeletal adverse events reported on the exercise program were considered to be related to participation in the physical activity program. 

“In patients with stage III or high-risk stage II colon cancer, a 3-year structured exercise program initiated shortly after completion of adjuvant chemotherapy improves disease-free survival, overall survival, patient-reported physical functioning, and health-related fitness. Health systems should incorporate structured exercise programs as standard of care for this patient population,” concluded the study authors. 

DISCLOSURE: Funding for this study was provided by the Canadian Cancer Society, the National Health and Medical Research Council, Cancer Research UK, and the University of Sydney Cancer Research Fund. For full disclosures of the study authors, visit meetings.asco.org.

REFERENCES

1. Booth CM, Vardy JL, O’Callaghan CJ, et al: A randomized phase III trial of the impact of a structured exercise program on disease-free survival in stage 3 or high-risk stage 2 colon cancer: Canadian Cancer Trials Group (CCTG) CO.21 (CHALLENGE). 2025 ASCO Annual Meeting. Abstract LBA3510. Presented during onsite press briefing May 31, 2025.

2. World Health Organization: Colorectal cancer: Key facts. Available at https://www.who.int/news-room/fact-sheets/detail/colorectal-cancer. Accessed May 16, 2025.

3. Colorectal Cancer Alliance: Colorectal cancer facts and statistics. Available at https://colorectalcancer.org/basics/facts-and-statistics#:~:text=The%20American%20Cancer%20Society%20estimates,increased%20screening%20and%20changing%20lifestyles. Accessed May 16, 2025.