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Structured exercise after adjuvant chemotherapy for colon cancer

31 October 2025

October’s Paper of the Month study adds to the data on the effect of structured exercise after adjuvant chemotherapy on disease-free survival in patients with stage II or III colon cancer.

Structured Exercise after Adjuvant Chemotherapy for Colon Cancer
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; CHALLENGE Investigators. Structured Exercise after Adjuvant Chemotherapy for Colon Cancer. N Engl J Med. 2025 Jul 3;393(1):13-25. doi: 10.1056/NEJMoa2502760. Epub 2025 Jun 1. PMID: 40450658.

What is known about the subject

  • Preclinical and observational studies suggest that exercise may improve cancer outcomes. However, until now, level 1 evidence from large randomised trials has been lacking.
  • Despite curative surgery and adjuvant chemotherapy, disease recurrence develops in 20 to 40% of patients with colon cancer [1].
  • Preclinical studies have shown that exercise can reduce the growth of cancers, including colon cancer [2-4].
  • Observational studies have shown that colorectal cancer patients who engage in higher levels of post-treatment physical activity have a lower risk of cancer recurrence and death [5].
  • Possible mechanisms underlying the association between post-treatment exercise and improved cancer outcomes include exercise’s effects on metabolic growth factors, inflammation, and immune function [6].

What the study adds

  • The CHALLENGE trial is a phase 3, multicentre, randomised study evaluating the effect of a 3-year structured, behaviourally supported exercise program compared with health-education materials alone in patients with stage II (high-risk) or stage III colon cancer who had completed adjuvant chemotherapy.
  • Patients in the health-education group received general health-education materials promoting physical activity and healthy nutrition in addition to standard surveillance. Those in the exercise group received the same materials plus an exercise guidebook developed for colon cancer survivors16 and support from a certified physical activity consultant for 3 years.
  • The goal of the exercise program was to increase recreational aerobic exercise from baseline by at least 10 metabolic equivalent task (MET)-hours per week during the first 6 months and then to maintain or further increase the amount during the final 2.5 years.
  • A total of 889 patients across 55 centers were randomly assigned to the exercise group (445 patients) or the health-education group (444 patients). The median follow-up was 7.9 years.
  • Disease-free survival was the primary end point of this study. The exercise group had a significantly longer disease-free survival compared with the health-education group (HR 0.72; 95% CI, 0.55 to 0.94; P=0.02).
  • Overall survival also favoured the exercise group (HR for death, 0.63; 95% CI, 0.43 to 0.94).
  • Patient-reported physical functioning, measured with the SF-36 physical-functioning subscale, improved more in the exercise group than in the health-education group at all time points up to 3 years.
  • The structured exercise program, combining aerobic and resistance training with behavioural support, was safe and feasible, with no increase in serious adverse events.

Implications for colorectal practice

  • This multicentre randomised trial showed that a 3-year structured exercise program initiated soon after adjuvant chemotherapy for colon cancer resulted in significantly longer disease-free survival and findings consistent with longer overall survival.
  • Structured exercise was safe and feasible, supporting its integration into survivorship care for colon cancer patients.
  • These findings provide level 1 evidence supporting the consideration of long-term, behaviourally supported exercise as part of post-treatment care for stage II–III colon cancer patients.

References

  1. Grothey A, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, et al. Duration of Adjuvant Chemotherapy for Stage III Colon Cancer. N Engl J Med. 2018;378(13):1177-88.
  2. Eschke RK, Lampit A, Schenk A, Javelle F, Steindorf K, Diel P, et al. Impact of Physical Exercise on Growth and Progression of Cancer in Rodents-A Systematic Review and Meta-Analysis. Front Oncol. 2019;9:35.
  3. Devin JL, Hill MM, Mourtzakis M, Quadrilatero J, Jenkins DG, Skinner TL. Acute high intensity interval exercise reduces colon cancer cell growth. J Physiol. 2019;597(8):2177-84.
  4. Orange ST, Jordan AR, Odell A, Kavanagh O, Hicks KM, Eaglen T, et al. Acute aerobic exercise-conditioned serum reduces colon cancer cell proliferation in vitro through interleukin-6-induced regulation of DNA damage. Int J Cancer. 2022;151(2):265-74.
  5. Markozannes G, Becerra-Tomás N, Cariolou M, Balducci K, Vieira R, Kiss S, et al. Post-diagnosis physical activity and sedentary behaviour and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis. Int J Cancer. 2024;155(3):426-44.
  6. Amirsasan R, Akbarzadeh M, Akbarzadeh S. Exercise and colorectal cancer: prevention and molecular mechanisms. Cancer Cell Int. 2022;22(1):247.