A structured exercise program after adjuvant chemotherapy in patients with high-risk stage II or III colon cancer improves both disease-free and overall survival, in results from the international Challenge Trial. Patients had a 37% lower risk for death if they participated in a structured exercise program, according to the study, which was presented at the 2025 annual meeting of the American Society of Clinical Oncology (abstract LBA3510), in Chicago.
“After completing surgery and chemotherapy, about 30% of patients with high-risk stage II and stage III colon cancer will eventually experience recurrence of their disease. As oncologists, one of the most common questions we get asked by patients is ‘What else can I do to improve my outcome?’ These results now provide us with a clear answer: An exercise program that includes a personal trainer will reduce the risk of recurrent or new cancer, make you feel better, and help you live longer,” said lead and presenting study author Christopher Booth, MD, a medical oncologist and health services researcher from the Queen’s University in Kingston, Ontario.
The CHALLENGE trial enrolled 889 participants from six countries, with most of them from Canada and Australia. The median age of the participants was 61 years and 51% were female. Of patients in the study, 90% had stage III colon cancer and 10% had high-risk stage II colon cancer. All patients had previously received intent-to-cure surgery and adjuvant chemotherapy within two to six months. There were no important differences in treatment or baseline characteristics between the two arms, according to Dr. Booth.
Patients underwent baseline fitness testing and then were randomized to participate in a structured exercise program (n=445) or to receive health education materials promoting physical activity and healthy nutrition (n=444) for three years. The behavior change program in the structured exercise program was delivered by a qualified personal trainer who gave each patient an exercise prescription that could involve various activities such as walking, depending on patient preference. Coaching sessions, which involved coaching and supervised exercise, occurred every two weeks in year 1 and then monthly for years 2 and 3. All participants also received standard cancer surveillance and follow-up care. The researchers monitored self-reported exercise increase by metabolic equivalent (MET) hours per week, and the target goal was for each patient to increase their exercise above their baseline by 10 MET hours per week.
“An exercise specialist would work with a patient to come up with an exercise prescription, taking into account their lifestyle, what activities they like to do, and what exercise habits they have had in the past,” Dr. Booth said. “This could account for any type of aerobic physical activity. They would figure out how many minutes and sessions each week would be required of walking, biking, running, swimming, cross-country skiing or even kayaking. Most patients chose a walking program, and they could reach their targets by going for a walk for 45 to 60 minutes three to four times per week.”
Adherence to the coaching sessions was 83% in the first six months of the trial, 68% in the next six months, and 63% in year 2 and 3. “The exercise program led to substantial and sustained increases in the amount of exercise that participants did, as well as physiologic measures of their fitness, with improved and very highly relevant improvements in VO2 max [maximal oxygen uptake] and their Six-Minute Walk Test,” Dr. Booth said. “The patients also felt better. The primary patient-reported outcome of physical function was also markedly improved and sustained during the intervention.”
The structured exercise program led to a 28% reduction in recurrent or new cancer (hazard ratio [HR], 0.72; P=0.017) with a five-year disease-free survival rate of 80% compared with 74% in the control group. For every 16 people, exercise prevented 1 person from developing recurrent or new cancer. There was also a 37% reduction in death (HR, 0.63; P=0.022); the eight-year overall survival rate was 90% compared with 83%. For every 14 people, exercise prevented 1 person from dying. The difference in survival was not driven by differences in cardiovascular deaths, but by reduction in the risk for death from colon cancer. The only safety signal was a slight increase in the risk for musculoskeletal symptoms in the structured exercise group (19% vs. 12%).
“The Challenge trial sets a new standard of care for colon cancer. A program of structured exercise after surgery and adjuvant chemotherapy meaningfully improves fitness, disease-free survival and overall survival,” Dr. Booth noted. “These results demonstrate a first-in-class, anti-cancer effect for a new form of cancer therapy. Moreover, the magnitude of benefit is substantial. It is comparable [to] and, in some cases, exceeds the magnitude of benefit of many of our very good, standard medical therapies in oncology.”
Dr. Booth added that knowledge alone will not change patient behavior or outcomes and that health systems need to invest in behavior support programs. “The policy implementation piece of this [is] key,” Dr. Booth said. “We need health systems, hospitals and payors to invest in these behavior support programs so that patients have access to a physical activity consultant and can realize the health benefits. This intervention is empowering and achievable for patients, and with much, much lower cost than our other therapies, it is also sustainable for health systems.”
According to Pamela Kunz, MD, a medical oncologist at the Yale School of Medicine, in New Haven, Conn., and an ASCO expert in gastrointestinal cancers, this is the first phase 3, randomized trial of patients with stage III and high-risk stage II colon cancer to demonstrate that post-treatment exercise is both achievable and effective in improving disease-free survival and overall survival. She called exercise, as an intervention, a “no-brainer” and said it should be implemented broadly.
—Kate O’Rourke
The sources reported no relevant financial disclosures.