Exercise is not just a tool to improve quality of life—it could become a key therapeutic intervention in oncology. This is demonstrated by the international CHALLENGE study (Colon Health and Life-Long Exercise Change), whose results were recently presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO) and published in the New England Journal of Medicine.
This controlled clinical trial randomized 889 stage II or III colon cancer survivors who had already completed their surgery and adjuvant chemotherapy. Participants, recruited from six countries (including Canada, Australia, and the United Kingdom), were divided into two groups: one received standard lifestyle counseling, while the other followed a supervised physical exercise program for three years.
The protocol included moderate aerobic activities, primarily 45- to 60-minute walks, 3 to 5 times per week, accompanied by regular follow-ups with specialized personal trainers. What stood out was not only the adherence to the program but its clinical impact: a 28% reduction in cancer recurrence risk and a 37% decrease in all-cause mortality in the group that engaged in structured exercise.
This finding challenges the traditional notion that, after completing cancer treatments, follow-up should focus solely on clinical exams and passive surveillance. The CHALLENGE study suggests that supervised physical activity has a physiological impact as powerful as some pharmacological interventions, influencing key processes such as inflammation, immune regulation, and insulin sensitivity.
From a biological standpoint, exercise modulates the tumor microenvironment and enhances the circulation of immune cells such as T lymphocytes and natural killer (NK) cells. It also reduces levels of systemic inflammatory cytokines (such as IL-6 and TNF-alpha), which have been associated with an increased risk of tumor progression. Additionally, exercise helps with weight control and improves gut microbiota—both factors linked to colorectal cancer recurrence.
Although this study focused on colon cancer, its implications could extend to other types of cancer, such as breast and prostate cancer, where a protective role of exercise has also been documented. Similar trials are already underway to evaluate these effects in different populations.
Figura 1. Structured exercise in colorectal cancer survivors reduced recurrence and mortality in the CHALLENGE trial. Benefits include improved immune response, lower inflammation and oxidative stress, better metabolism, and gut microbiota modulation.
In oncology, adjuvant therapies are designed to reduce the chance of recurrence after curative treatment. While adjuvant drugs like oxaliplatin or capecitabine target residual tumor cells, exercise may act on the biological terrain where those cells seek to re-emerge: the inflammatory environment, the immune system, and the host’s metabolism.
This study also challenges the idea that effective interventions must be exclusively pharmacological. Exercise, when prescribed and supervised, can have effects equivalent to or even greater than some adjuvant drugs—without the classic side effects.
Although the CHALLENGE study focused on colon cancer, it lays the foundation for replicating the model in breast, prostate, lung, and other solid tumors, where growing evidence supports the protective role of exercise. In fact, several ongoing clinical trials are evaluating biomarkers of inflammation, immune competence, and gut microbiota as predictors of response to oncological exercise interventions.
Main Reference:
Christopher M. Booth et al. A randomized phase III trial of the impact of a structured exercise program on disease-free survival (DFS) in stage 3 or high-risk stage 2 colon cancer: Canadian Cancer Trials Group (CCTG) CO.21 (CHALLENGE).. JCO 43, LBA3510-LBA3510(2025).
https://ascopubs.org/doi/10.1200/JCO.2025.43.17_suppl.LBA3510
