An international study shows that cancer survivors who get moving after chemo can increase their chances of beating colon cancer, making exercise a game-changer for long-term survival.
Study: Structured Exercise after Adjuvant Chemotherapy for Colon Cancer. Image credit: Simplylove/Shutterstock.com
A recent New England Journal of Medicine study conducted a phase 3 randomized trial to assess how structured exercise programs after adjuvant chemotherapy impact prolonged disease-free survival in colon cancer patients.
Colorectal cancer: Conventional treatment and relapse
Colorectal cancer, also known as bowel cancer, is the third most common type of cancer worldwide and has high mortality rates. Typically, patients with stage III or high-risk stage II colon cancer are recommended surgery and adjuvant chemotherapy.
Soon after surgery, these patients are treated with capecitabine and oxaliplatin (CAPOX), 5-fluorouracil and oxaliplatin (FOLFOX), or monotherapy fluoropyrimidine for three to six months. In addition to side effects, this treatment strategy has a high relapse rate. Therefore, new interventions are urgently needed to improve these patients' quality of life and survival rate.
Preclinical studies have demonstrated the beneficial effects of exercise in reducing cancer growth. Observational studies have also shown that colorectal cancer patients who engage in recreational physical activity after treatment are at a lower risk of cancer relapse and death.
However, previous evidence from observational studies could not definitively prove a causal relationship due to limitations in study design. More research is essential to understand how exercise improves colorectal cancer outcomes after surgery and adjuvant chemotherapy.
About the study
The Canadian Cancer Trials Group (CCTG) launched the CO.21 Colon Health and Lifelong Exercise Change (CHALLENGE) trial to compare the effects of health-education materials alone (health education) or these materials in combination with a structured exercise program (exercise) for over three years in patients with colon cancer who had completed adjuvant chemotherapy.
All participants completed resection of stage III or high-risk stage II adenocarcinoma of the colon, followed by adjuvant chemotherapy. These patients exercised less than 150 minutes per week of moderate-to-vigorous intensity at baseline.
Eastern Cooperative Oncology Group (ECOG) used a 5-point scale approach to assess the degree of disability. Higher numbers on this scale indicated greater disability. All eligible patients could complete at least a 6-minute walk test or two stages of a submaximal treadmill test.
Patients were randomly assigned to health education and exercise groups in a 1:1 ratio using a dynamic minimization procedure. Patients assigned to the health education group received materials linked to physical activity and healthy nutrition. In contrast, those in the exercise group received the same materials and an exercise guidebook developed for colon cancer survivors. Exercise group participants also received support from a certified physical activity consultant for three years.
The support program was divided into three phases based on the timeline and defined support. During the program's first six months (phase 1), exercise group participants attended 12 mandatory in-person behavioral support sessions scheduled every two weeks, 12 compulsory supervised exercise sessions, and an additional 12 supervised exercise sessions during alternate weeks.
During the second six months of the program (phase 2), patients attended 12 mandatory behavioral support sessions, in person or remotely, every two weeks, along with a supervised exercise session if they attended in person.
In the last two years of the study (phase 3), patients had to participate in 24 compulsory monthly in-person or remote behavioral-support sessions, combined with a supervised exercise session in case the patient attended in person.
The exercise program aimed to raise recreational aerobic exercise from baseline by at least ten metabolic equivalent tasks (MET) hours per week for the first two quarters. Subsequently, the goal was to maintain or further increase this during the remaining 2.5 years.
Study findings
Between 2009 and 2024, 889 patients were recruited from 55 sites in Canada and Australia. In this study, 445 patients were randomly assigned to the exercise group, and 444 were assigned to the health-education group. The median age of the patients was 61 years; 90% of the cohort had stage III disease, and 61% had received FOLFOX treatment.
During Phase 1, the Intervention Adherence and Changes in Physical Activity Adherence was estimated to be 83% for the 12 mandatory behavioral-support sessions, 79% for the 12 mandatory supervised exercise sessions, and 20% for the 12 recommended supervised exercise sessions.
During phase 2, adherence fell to 68% for the 12 compulsory behavioral-support sessions and 54% for the 12 recommended supervised exercise sessions. Adherence rates in Phase 3 were 63% for the 24 mandatory behavioral support sessions and 44% for the 24 recommended supervised exercise sessions.
A regression model indicated that patients in the exercise group maintained larger improvements than those in the health-education group over the entire three-year intervention. These improvements were in accordance with moderate-to-vigorous physical activity, maximum oxygen consumption, and a 6-minute walk distance.
The difference in recreational moderate-to-vigorous physical activity between groups ranged from 5.2 to 7.4 MET hours per week. The predicted maximum oxygen consumption improved from 1.3 to 2.
7 ml/kg/min, and the between-group difference in 6-minute walk distance ranged from 13 to 30 meters. Minimal between-group differences were observed for body weight or waist circumference.
At a median follow-up of 7.9 years, 93 and 131 patients in the exercise group and the health-education group, respectively, underwent disease recurrence, new primary cancer, or death. This corresponded to a hazard ratio for disease recurrence, new primary cancer, or death of 0.72, favoring the exercise group.
Notably, five-year disease-free survival was significantly longer in the exercise group (80.3%) compared to the health education group (73.9%). The exercise group also improved overall survival, with a hazard ratio for death of 0.63. The 8-year overall survival was 90.3% in the exercise group and 83.2% in the health-education group.
Furthermore, patients in the exercise group exhibited greater improvements from baseline concerning the physical-functioning subscale than those in the health-education group. At six months, the improvement in the SF-36 physical-functioning subscale was 7.1 points for the exercise group and 1.3 points for the health-education group. These improvements persisted over three years.
Safety analysis revealed that 82.0% of patients in the exercise group and 76.4% in the health-education group experienced at least one adverse event of any grade.
Musculoskeletal adverse events occurred in 18.5% of patients in the exercise group and 11.5% in the health-education group. Only 10% of musculoskeletal events in the exercise group were related to the exercise intervention. Grade three or higher adverse events occurred in 15.4% of the exercise group and 9.1% of the health-education group.
Limitations of the study include slow recruitment, selection bias toward higher-functioning patients, and a lower-than-expected event rate. The exercise group also received more social contact through behavioral support, which may have had some influence.
Additionally, self-reported physical activity is subject to recall bias. The study did not assess whether starting exercise before or during chemotherapy would yield similar or greater benefits. The exercise program initiated soon after adjuvant chemotherapy resulted in significantly longer disease-free survival in colon cancer patients.
The results also support improved overall survival and physical functioning, with a manageable increase in musculoskeletal adverse events.
Conclusion
Structured exercise programs started soon after chemotherapy significantly improved disease-free and overall survival for colon cancer patients compared to patients that only receive standard health education alone.
This provides a powerful, evidence-based strategy for colon cancer survival, emphasizing the need to invest in structured behavior-support exercise programs to understand the full benefits.
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