Structured Exercise After Chemotherapy: A Turning Point in Colon Cancer?
Physical activity has long been associated with better metabolic, cardiovascular, and functional health. In oncology, it is also playing an increasingly important role in reducing fatigue, preserving physical capacity, and improving quality of life during or after treatment. In colorectal cancer, this issue is particularly important: even after surgery and adjuvant chemotherapy, a significant proportion of patients (20–40%) experience a recurrence or develop a new cancer, while treatments can leave lasting effects on physical condition.
Until now, much of the evidence supporting exercise has come from observational studies. These studies often showed that patients who were more active after diagnosis had a lower risk of recurrence or death. But this type of evidence remains fragile: patients capable of moving more are sometimes also those with a less aggressive disease, better initial health, fewer comorbidities, or better access to care. In other words, physical activity could be a marker of a better prognosis as much as a genuine therapeutic intervention. So, in patients who have undergone surgery for colon cancer and completed adjuvant chemotherapy, can a structured, supervised, and prolonged exercise program actually improve disease-free survival, beyond simply providing health education?
The study
The CHALLENGE trial is a phase 3 randomized study conducted at 55 centers, primarily in Canada and Australia. It included 889 patients who had undergone complete resection of stage III or high-risk stage II colon cancer, followed by adjuvant chemotherapy completed within 2 to 6 months prior to enrollment. Participants had preserved functional status and reported engaging in less than the equivalent of 150 minutes per week of moderate-to-vigorous physical activity.
Patients were divided into two groups. The control group received health education materials on physical activity, nutrition, and standard follow-up. The intervention group received the same materials, but also a 3-year structured exercise program supported by a certified physical activity consultant. The intervention was therefore not a simple recommendation to “move more,” but rather progressive behavioral support designed to establish and then maintain a lasting increase in physical activity.
The program aimed for an increase of at least 10 MET-hours per week of recreational aerobic exercise compared to baseline levels. In practice, this corresponds approximately to adding 45 to 60 minutes of brisk walking 3 to 4 times a week, or 25 to 30 minutes of jogging 3 to 4 times a week. The activity was individualized: participants could choose the type, frequency, intensity, and duration of the exercise, with an emphasis on at least moderate-intensity aerobic exercise, such as brisk walking.
The first phase, during the first 6 months, was the most intensive: behavioral support sessions every two weeks, mandatory supervised sessions, and recommended supervised sessions. The second phase, from 6 to 12 months, maintained follow-up every two weeks, either in person or remotely. The third phase, over the following two years, involved monthly follow-up, with supervision available as needed. The goal was therefore not merely to produce an acute effect, but to achieve lasting behavioral change over several years.
The primary endpoint was disease-free survival, defined as the time to recurrence of colorectal cancer, a new primary colorectal cancer, a second primary cancer, or death from any cause. Secondary endpoints included overall survival, patient-reported physical function, cardiorespiratory fitness, distance on the 6-minute walk test, and moderate-to-vigorous physical activity.
Results & Analyses
After a median follow-up of 7.9 years, disease-free survival was significantly better in the exercise group. An event (recurrence, new primary cancer, or death) occurred in 93 patients in the exercise group compared with 131 in the health education group. The hazard ratio was 0.72, with a 95% confidence interval of 0.55 to 0.94. This corresponds to a 28% relative reduction in the risk of an event. At 5 years, disease-free survival was 80.3% in the exercise group versus 73.9% in the control group. The annual incidence of events was 3.7% in the exercise group versus 5.4% in the health education group.
Overall survival, a major secondary endpoint, showed a similar trend. A total of 41 deaths occurred in the exercise group compared with 66 in the control group. The hazard ratio for death was 0.63, with a 95% confidence interval of 0.43 to 0.94. At 8 years, overall survival was 90.3% in the exercise group compared with 83.2% in the health education group.
The improvement in disease-free survival appears to be primarily linked to a reduction in liver recurrences and new primary cancers. Liver recurrences were less frequent in the exercise group, with 16 cases compared to 29 in the control group. New primary cancers were also less common, with 23 cases compared to 43. In contrast, deaths without recurrence or new primary cancer were similar between the groups. This distribution suggests that the observed benefit could be linked to effects on the cancer progression itself, but this interpretation remains cautious, as these analyses do not replace the primary endpoint.
The intervention also achieved its behavioral objective. Patients in the exercise group increased and maintained their moderate-to-vigorous physical activity over the 3-year period. Differences between groups ranged from 5.2 to 7.4 MET-hours per week, which is equivalent to approximately 1.5 to 2.25 additional hours of walking at 4.8 km/h per week compared to the control group. Clinical benefit was observed where changes in physical activity actually occurred and were sustained over time.
Predicted cardiorespiratory fitness was higher in the exercise group, with differences between groups ranging from 1.3 to 2.7 ml/kg/min depending on the measurement time point. The distance covered in the 6-minute walk test also improved more significantly, with differences ranging from 13 to 30 meters. Physical function as reported by patients followed the same trend, with greater improvements in the exercise group throughout most of the intervention.
Differences in body weight and waist circumference were minimal. This makes it unlikely that the observed effects can be explained simply by weight loss. Exercise may act through other mechanisms, such as improved insulin sensitivity, modulation of inflammation, immune surveillance, or effects on the tumor microenvironment and metastatic sites. The study mentions these mechanisms as plausible but does not directly demonstrate them in the main analysis. Planned biological analyses of blood samples could help clarify these pathways.
Regarding the safety of the intervention, musculoskeletal adverse events were naturally more frequent in the exercise group: 18.5% versus 11.5%. However, among the musculoskeletal events reported in the exercise group, only 8 out of 79 were considered related to the intervention. This serves as a reminder that exercise, especially in patients recovering from intensive treatments, requires individualized prescribing, appropriate progression, and realistic monitoring.
The limitations are important for understanding to whom the results apply. Participants were functional enough to join an exercise program and had to be able to complete a basic physical test. The study therefore does not directly address patients who are very frail, highly symptomatic, or have major functional impairment. Furthermore, enrollment occurred 2 to 6 months after chemotherapy, which excludes very early recurrences and the most aggressive cancers. We cannot conclude that the same effect would be observed if exercise were started before surgery or during chemotherapy.
It should also be noted that the exercise group benefited from more contact with professionals. It is therefore difficult to completely rule out an effect related to social support, the attention received, or overall care. The authors emphasize, however, that other psychosocial or nutritional interventions in oncology, despite a high volume of contact, have not shown a comparable benefit on survival. Finally, physical activity was partly measured through self-reported recall, which always carries a risk of inaccuracy, even though objective improvements in physical fitness and function support the reality of the change.
Practical Applications
This study not only shows that physical activity improves fitness or quality of life; it provides a high level of evidence indicating that a structured, supervised program maintained over 3 years can improve disease-free survival in patients who have undergone surgery and received adjuvant chemotherapy.
The observed benefit is based on an organized intervention: quantified goals, behavioral support, gradual progression, long-term follow-up, and individualized exercise. The study suggests that a realistic increase—approximately 10 MET-hours per week above the baseline level—may be appropriate, but this increase must be tailored to the patient’s condition, preferences, pain, fatigue, comorbidities, and activity history.
For a patient comparable to those in the study, the practical goal could be to gradually add several weekly sessions of moderate-intensity aerobic exercise, such as brisk walking, until a sustainable volume is reached. The choice of activity is important: the study does not validate a specific activity, but rather a lasting change. Brisk walking is therefore a credible, accessible tool consistent with the protocol, provided that the intensity is truly at least moderate and that the volume is maintained.
In clinical practice, this study supports the integration of structured physical activity programs into the care pathway following adjuvant chemotherapy for colorectal cancer. But it also reminds us that information alone is likely insufficient. The control group was already receiving health materials and also improved their physical activity, but to a lesser extent than the supervised group. The difference between the groups shows that behavioral support, follow-up, and program structure can make a difference.
In conclusion, structured exercise is associated with a significant improvement in disease-free survival and results consistent with better overall survival. However, this effect was achieved within a specific framework, among selected patients, with long-term support, and at the cost of a slight increase in musculoskeletal events. Exercise is not a substitute for oncological treatments but a healthcare intervention in its own right, which deserves to be prescribed, supervised, and evaluated with the same seriousness as other components of the therapeutic pathway.
Reference
Courneya KS, Vardy JL, O’Callaghan CJ, Gill S, Friedenreich CM, Wong RKS, Dhillon HM, Coyle V, Chua NS, Jonker DJ, Beale PJ, Haider K, Tang PA, Bonaventura T, Wong R, Lim HJ, Burge ME, Hubay S, Sanatani M, Campbell KL, Arthuso FZ, Turner J, Meyer RM, Brundage M, O’Brien P, Tu D & Booth CM. Structured Exercise after Adjuvant Chemotherapy for Colon Cancer. N Engl J Med 393:13-25, 2025.
