Definitive evidence of improved patient outcomes has been found, and the results are significant.
Eight years after successful colon cancer treatment, the rates of disease recurrence, new primary cancer or death from any cause were 28% lower for patients who had participated in a structured exercise program.
The phase three CHALLENGE trial by the Canadian Cancer Trials Group is the first to provide definitive evidence of what has been inconclusively suggested from previous observational studies.
Researchers concluded that exercise reduced the relative risk of death by 37% – an effect similar in size to many currently approved standard drug treatments. The five-year disease-free survival rate was 80% in the exercise group and 74% in the health education group and at eight years, was 90% and 83% respectively.
“This study provides irrefutable, level one evidence that structured exercise improves outcomes in colorectal cancer,” Dr Prasad Cooray, Melbourne oncologist and clinical lecturer at the University of Melbourne’s department of surgery, told Oncology Republic.
“While this study confirms the survival benefit of exercise after treatment, it also opens opportunities for a broader truth: exercise should be embedded across the entire colorectal cancer pathway, from pre-op to post-chemo and beyond. This is no longer just an adjunct. It is an intervention with measurable impact, and it’s time we treated it as such.”
He said that what stood out most was the magnitude of the benefit; nearly an 8% absolute improvement in disease-free survival is both statistically and clinically significant.
“To put that into perspective, this is double the benefit we saw when oxaliplatin (FOLFOX) was added to 5-FU chemotherapy in adjuvant setting, a change that shifted global practice,” he said.
“My hope is that we now respond with the same level of urgency and commitment, placing exercise where it belongs, at the heart of routine cancer care.”
Between 2009 and 2024, nearly 900 patients who had completed adjuvant chemotherapy within the past two to six months were recruited across 55 sites, mostly in Canada and Australia.
Participants had complete resection of stage III or high-risk stage II adenocarcinoma of the colon, had an Eastern Cooperative Oncology Group performance-status score of 0 or 1, were completing less than 150 minutes per week of moderate to vigorous exercise and were able to complete at least two stages of a six-minute walk test.
Participants were randomised, with half receiving health education materials only and half receiving a three-year structured exercise program along with their education materials. The materials promoted physical activity and healthy nutrition, but the exercise program was a guidebook developed specifically for colon cancer survivors. In addition, the exercise group had mandatory (and optional extra) access to a certified physical activity consultant for the three-year program duration.
The program consisted of three phases, guided by the Theory of Planned Behaviour, consisting of 17 evidence-based techniques for behavioural change. The goal was to increase aerobic exercise from baseline by a minimum of 10 metabolic equivalent task-hours (MET-hours) per week in the first six months and then maintain or increase that over the rest of the program period.
METs were used to indicate the intensity of exercise, with brisk walking approximating four METs. An hour of this activity has a value of four MET-hours. Activities were considered moderate-to-vigorous if they had MET values of three of more, and patients chose the type, frequency, intensity and duration of their exercise.
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Phase one was the first six months of the program, consisting of 12 mandatory in-person behavioural support sessions every fortnight, 12 mandatory supervised exercise sessions and 12 optional (recommended) supervised exercise sessions on the alternate weeks.
Phase two was the following six months; 12 mandatory behavioural-support sessions (either in person or remotely by telephone or video) every fortnight, with those attending in-person undergoing a supervised exercise session.
The final phase was over the next two years and consisted of 24 mandatory monthly in-person or remote behavioural-support sessions, with supervised exercise sessions for those attending in-person.
Baseline physical activity was assessed for the month prior to the start of the program using the Total Physical Activity Questionnaire, with repeat assessments at six months and one-, two- and three-year checkpoints. Cardiorespiratory fitness, body weight and circumferences and objective physical functioning were also assessed at these times.
Musculoskeletal events occurred in 18% of the exercise group compared with 11% of the education group, but only 10% of those in the exercise group were considered related to the intervention.
“We also can’t ignore the role of exercise in surgical recovery. As part of both prehabilitation and rehabilitation, it improves mobility, reduces complications, and helps patients return to baseline faster,” said Dr Cooray.
He said that it is well-known that exercise during chemotherapy enhances treatment tolerance, reduces side effects and helps maintain dose intensity, but that this is particularly relevant in colorectal cancer, where adjuvant therapies like oxaliplatin can cause debilitating neuropathy, and capecitabine can lead to sensory dysfunction through hand-foot syndrome.
“I believe the next step is clear: bring exercise earlier into the treatment journey, not just afterwards.”
