Colorectal cancer (cancer of the colon or rectum) is one of the most common cancers and the second leading cause of cancer-related death worldwide. For stage II and III tumors, standard treatment includes surgery followed by chemotherapy for 3–6 months (FOLFOX, CAPOX, or fluoropyrimidine monotherapy). Despite the effectiveness of these regimens, recurrence occurs in 20–40% of patients. In addition, chemotherapy often causes side effects that reduce quality of life and limit physical activity. Therefore, physicians are seeking interventions that not only prolong life but also improve well-being after treatment.
Animal studies have shown that physical exercise can slow tumor growth, including colorectal cancer. Observational studies in humans have also found that patients who maintain regular physical activity after treatment experience fewer recurrences and live longer. This may be due to the effects of exercise on metabolism, inflammation, and the immune system. However, these data are observational and cannot conclusively prove causation, as confounding factors cannot be excluded entirely.
Study Design
To obtain more definitive results, the Canadian Cancer Trials Group (CCTG) conducted a significant phase III randomized controlled trial called CHALLENGE (Colon Health and Lifelong Exercise Change). Participants were patients who had completed adjuvant chemotherapy after colorectal cancer.
Participants
Patients with completely respected stage II (T4, poorly differentiated, with <12 lymph nodes removed) or stage III colon adenocarcinoma were eligible. All participants had completed adjuvant chemotherapy 2–6 months before enrollment, had no physical limitations, and reported performing less than 150 minutes per week of moderate or vigorous physical activity. Each participant completed at least two stages of a 6-minute walking test at a normal pace.
Intervention
Participants were randomly assigned to one of two groups:
- Health Education Group (444 participants): Received only educational materials on healthy living.
- Exercise Group (445 participants): Received the same materials plus a three-year structured exercise program designed explicitly for colorectal cancer survivors. The program was based on the Theory of Planned Behavior and included 17 evidence-based behavioral change techniques previously shown to increase physical activity levels effectively.
The program consisted of three phases:
- Phase 1 (first 6 months): Twelve mandatory in-person behavioral support sessions every two weeks, twelve supervised exercise sessions, and twelve additional recommended sessions.
- Phase 2 (next 6 months): Twelve mandatory support sessions (in-person or remote) every two weeks, combined with supervised exercise for in-person participants.
- Phase 3 (final 2 years): Twenty-four monthly in-person or remote support sessions, with supervised exercise for those attending in person.
The main goal was to increase aerobic activity by at least 10 metabolic equivalents (MET-hours) per week during the first six months and maintain or improve this level thereafter. One hour of brisk walking equals 4 MET-hours, meaning that participants needed to add roughly 2.5 hours of brisk walking per week. Participants could choose their preferred type, frequency, duration, and intensity of aerobic exercise (e.g., treadmill, stationary bike, or elliptical trainer).
Physical Outcomes
Participants in the exercise group achieved and maintained greater improvements than those in the health education group throughout the three-year follow-up. They showed larger increases in moderate-to-vigorous physical activity (by 5.2 – 7.4 MET-hours per week), higher maximal oxygen consumption (VO₂max; by 1.3 – 2.7 mL/kg per minute), and longer six-minute walking distances (by 13–30 meters).
Survival and Disease Outcomes
After a median follow-up of 7.9 years, cancer recurrence, new primary malignancy, or death occurred in 224 patients – 93 in the exercise group and 131 in the health education group. A total of 107 participants died from any cause: 41 in the exercise group and 66 in the health education group.
Disease-free survival was significantly higher among exercise participants, whose risk of recurrence, new cancer, or death was 28% lower than that of controls. The annual rate of recurrence, new cancer, or death was 3.7% versus 5.4%. The five-year disease-free survival rate was 80.3% in the exercise group versus 73.9% in the control group.
Overall survival was also better: participants in the exercise group had a 37% lower risk of death from any cause. The annual mortality rate was 1.4% versus 2.3%, and eight-year overall survival was 90.3% versus 83.2%.
Quality of Life and Physical Functioning
These were assessed using the SF-36 questionnaire, where higher scores indicate better functioning. Participants in the exercise group reported more pronounced and sustained improvements compared with baseline. Differences between groups persisted throughout the three-year observation period:
- At 6 months, +7.1 vs. +1.3 points in the health education group
- At 1 year – +6.8 vs. +3.3
- At 18 months – +7.2 vs. +2.4
- At 2 years – +6.1 vs. +2.6
- At 3 years – +6.1 vs. +3.0
Safety Analysis
At least one adverse event of any grade occurred in 82.0% of exercise participants and 76.4% of those in the health education group. Musculoskeletal adverse events were reported in 18.5% of the exercise group and 11.5% of the control group, but only about 10% of these were directly related to exercise. Severe (grade ≥3) adverse events were observed in 15.4% of the exercise group versus 9.1% of controls.
Conclusion
A three-year program of regular exercise in patients who had completed chemotherapy significantly improved disease outcomes. Participants who exercised had a 28% lower risk of recurrence, new primary cancer, or death compared with controls. Five-year disease-free survival was 80% versus 74%, and eight-year overall survival was 90% versus 83%.
The most significant benefit came from reduced recurrences and new tumors, particularly liver, breast, and prostate cancers. This effect may be explained by exercise-mediated reductions in inflammation, enhanced immune surveillance, improved insulin sensitivity, and changes in metastatic microenvironments that make them less favorable for tumor growth. Specifically, exercise may modulate metabolic growth factors such as insulin and insulin-like growth factors that promote cancer cell proliferation and progression.
The exercise program consisted of moderate-intensity aerobic activity – for example, brisk walking for 45–60 minutes or jogging for 25–30 minutes three to four times per week. It improved physical endurance and well-being without significant changes in body weight, suggesting that weight loss is unlikely to explain the observed survival benefits.
Musculoskeletal side effects were only slightly more frequent in the exercise group and were mostly mild. Regular exercise after colorectal cancer treatment is safe and significantly improves survival and quality of life. These findings support integrating exercise programs into the standard supportive care for cancer survivors.
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Reference
Structured Exercise after Adjuvant Chemotherapy for Colon Cancer
