Colorectal cancer is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths globally. Usually, patients diagnosed with stage III or high-risk stage II colon cancer typically undergo surgery followed by several months of adjuvant chemotherapy with regimens such as FOLFOX or CAPOX. Unfortunately, 20–40% of treated patients experience a recurrence of their cancer, and the overall invasiveness of treatment significantly affects long-term quality of life.
An unprecedented international study may change the standard of care for these patients based on the treatment that follows the management of their disease. The CHALLENGE trial, developed and conducted by the Canadian Cancer Trials Group, investigated whether a supervised exercise program could improve function and survival in colon cancer survivors. Nearly 889 patients from 55 sites worldwide were enrolled between 2009 and 2024. Following enrollment, patients were randomly assigned to either a health education group or a health education group combined with a 3-year structured supervised exercise program.
Participants in the exercise group, supported by certified exercise consultants, gradually increased their physical activity over the 3 years to achieve a target of an additional 10 MET-hours per week, equivalent to brisk walking or light jogging. Fitness markers in the exercise group showed progressive improvements over time, including cardiorespiratory improvements of 1.3–2.7 ml/kg/min and 6-minute walk improvements of 13–30 m.
The positive effects of exercise on cancer outcomes were apparent after a median follow-up of 7.9 years. In the exercise group, the 5-year disease-free survival was 80.3% compared to 73.9% in the control (hazard ratio [HR] 0.72; 95% confidence interval [CI], 0.55 – 0.94; P = 0.02). The overall survival showed an even more striking result at 8 years, survival was 90.3% for the exercise group vs. 83.2% in the control group (HR 0.63; 95% CI, 0.43-0.94). These represent relative gains of 28% and 37%, respectively, comparable to outcomes seen with some conventional cancer therapies.
The exercise group also showed greater and sustained improvements in patient-reported physical functioning (SF-36 scores) throughout the 3-year intervention. These improvements peaked at 6 months with a 7.1-point increase compared to 1.3 points in the control group.
While 82% of exercise participants experienced adverse events (compared to 76.4 % in the control group), most were mild. Musculoskeletal adverse events were more common in the exercise group (18.5% vs. 11.5%), but only 10% were directly attributed to the intervention. Severe adverse events (grade 3 or higher) occurred in 15.4 % of the exercise group and 9.1% of the control group.
The likely biological mechanisms underlying these effects include enhanced immune function, reduced inflammation, enhanced insulin sensitivity, and a tumor microenvironment that is less conductive to micrometastatic growth. These effects were associated with a lower incidence of liver metastases and reduced risk for new primary cancers (breast, prostate, and colorectal). Although the health education group modestly increased physical activity, the data clearly demonstrate that structured, supervised support was significantly more effective.
Limitations of this study included a prolonged 15-year enrollment period, reliance on self-reported activity data, and potential selection bias toward healthier participants. Nevertheless, objective measures of fitness provided accountability for the reported changes in behaviours.
In conclusion, this pioneering trial provides robust evidence that structured exercise should be an integral part of survivorship care for individuals with colon cancer. Structured physical activity enhances the quality of life and offers survival benefits compared to medical treatments, without the associated toxicity.
References: Courneya KS, Vardy JL, O’Callaghan CJ, et al. Structured exercise after adjuvant chemotherapy for colon cancer. N Engl J Med. 2025. doi:10.1056/NEJMoa2502760
