While observational studies have long hinted at the potential for physical activity (PA) to reduce cancer recurrence, robust clinical evidence has remained limited, often confounded by bias and lack of rigor.¹ To address this gap, the Canadian Cancer Trials Group (CCTG) launched the randomized phase 3 CHALLENGE trial (CO.21), a randomized phase 3 study evaluating whether a structured exercise program (SEP) initiated after adjuvant chemotherapy could improve disease-free survival (DFS) in patients with resected stage 3 or high-risk stage 2 colon cancer.¹ The results were presented by Dr. Christopher M. Booth from Queen's University in Kingston, Ontario, at the 2025 ASCO Annual Meeting.¹

The CHALLENGE trial enrolled 889 patients across 55 sites in six countries.¹ All participants had completed adjuvant chemotherapy and were randomized to receive either health education materials (HEM) promoting general PA and nutrition (n=444) or a 3-year SEP (n=445) delivered by trained physical activity consultants.¹ The SEP aimed to increase recreational PA by at least 10 MET-hours per week during the first 6 months (1 MET-hour represents the energy expended sitting quietly for 1 hour; by comparison, 1 hour of brisk walking equals roughly 4 MET-hours), followed by individualized targets in phases 2 and 3, with upper limits of 20 and 27 MET-hours per week, respectively.¹ Participants could choose the type, frequency, intensity, and duration of aerobic activities to suit their preferences.¹

The primary endpoint was DFS, assessed on an intention-to-treat basis.¹ Secondary endpoints included overall survival (OS), predicted VO2max, 6-minute walk distance, and patient-reported physical function measured using the SF-36 physical function subscale.¹ Baseline characteristics were well-balanced between groups, where the median age was 61 years, 51% of participants were female, and 90% had stage 3 disease.¹ After a median follow-up of 7.9 years, the SEP group demonstrated clear survival benefits.¹ DFS events occurred in 93 SEP participants vs. 131 in the HEM group.¹ The 5-year DFS rate was 80% in the SEP group compared to 74% in the control group (HR=0.72; 95% CI: 0.55-0.94; p=0.017).¹ OS also improved with exercise: the 8-year OS rate was 90% with SEP vs. 83% with HEM (HR=0.63; 95% CI: 0.43-0.94; p=0.022).¹

The SEP group also reported significant and sustained improvements in health-related fitness and physical function.¹ At 6 months, SF-36 physical function scores increased by 7.42 points in the SEP group compared to 1.10 points in the HEM group (p<0.001), with benefits maintained through 24 months.¹ Objective measures such as predicted VO2max and 6-minute walk distance also favored the SEP group.¹ Musculoskeletal adverse events (AEs) were reported in 19% of SEP participants (79/428) vs. 12% in the HEM group (50/433).¹ However, only 10% of these AEs in the SEP group were considered related to the exercise program, and no serious safety issues were identified.¹

In conclusion, the CHALLENGE trial provides strong evidence that a long-term SEP after adjuvant chemotherapy significantly improves DFS, OS, cardiorespiratory fitness, and physical functioning in patients with early-stage colon cancer.¹ Accordingly, these findings support the integration of supervised exercise into standard survivorship care.¹

In an interview with Omnihealth Practice, Dr. Matin Mellor Abdullah, a senior consultant clinical oncologist from Malaysia, reflected on the growing evidence supporting structured exercise in cancer care, in light of the CHALLENGE trial findings.

Q1: How commonly do cancer patients in your practice receive structured or supervised exercise guidance?
Dr. Matin Mellor: Currently, most patients only receive general advice—typically 150 minutes of moderate-intensity activity per week, like brisk walking. However, we rarely distinguish between different types of exercise, such as aerobic vs. resistance training, or offer tailored prescriptions. In my view, mixed-type exercise offers the greatest benefit, yet structured and personalized programs remain uncommon in daily practice.

Q2: What could be the clinical rationale for integrating exercise into cancer care?
Dr. Matin Mellor: There are several possible compelling reasons. Exercise supports mental health, helps combat depression, and can alleviate certain chemotherapy-related side effects such as numbness. While earlier studies suggested benefits, many lacked methodological rigor. That is why the CHALLENGE trial is significant—it offers robust, phase 3 evidence that could help standardize exercise recommendations in survivorship care.

Q3: What are the current barriers to implementation, and how might this change moving forward?
Dr. Matin Mellor: Ideally, a SEP should be part of a multidisciplinary care model, but at the moment, that is not easy to implement. Rehabilitation physicians do not typically work with cancer patients on a regular basis, and oncology teams may not have the training to prescribe individualized exercise regimens. As such, the advice we give often stays quite general.

From my point of view, holistic cancer care needs to go beyond just drugs. We should be supporting patients in all aspects—psychological well-being, sexual health and fertility, dietary guidance, and physical activity. For example, we often advise patients to avoid raw food and opt for clean, fresh sources, but broader lifestyle conversations still tend to be limited.

In practice, many patients, especially those with advanced disease, are also exploring complementary approaches like herbal supplements, mushroom extracts, turmeric, or vitamin C. Others turn to movement-based practices such as Qigong or Tai Chi, which they find helpful. While the evidence for some of these is variable, I think it reflects a desire for care that is more personalized and empowering. A well-structured exercise program could fit naturally into that kind of survivorship model, but it would need to be supported at both the system and community level. Patient support groups could be very helpful in driving that forward.