Exercise in CRC Survivors: A Closer Look at Biomarker Effects

A randomized trial published in the Journal of Sport and Health Science in March 2025 investigated whether moderate-intensity aerobic exercise can influence systemic inflammation and tumor-related biomarkers in colorectal cancer (CRC) survivors. While prior studies have linked physical activity with reduced recurrence and mortality in CRC, the biological mechanisms behind this association have not been clearly established.

This trial, known as the Exercise and Colorectal Cancer Treatment (EXACT) study, examined the effects of a 12-week home-based exercise program on inflammation, circulating tumor cells (CTCs), and circulating tumor DNA (ctDNA).

Study Design and Intervention

60 participants who had completed treatment for stage I to III colorectal cancer (mean age 60.6 years, 65% female) were randomized to either a home-based aerobic exercise group or a waitlist control group. The intervention included use of an in-home treadmill, a heart rate monitor, and weekly behavioral support from exercise specialists. Adherence was high, with participants averaging 124 minutes of exercise per week and 92% compliance.

Participants in the exercise group showed improved submaximal cardiopulmonary fitness capacity (+0.36 metabolic energy expenditure [METs], p = 0.025) and a 34.8% increase in moderate-to-vigorous physical activity compared to control (p = 0.002).

Inflammatory and Tumor Biomarker Outcomes

The primary biomarkers of interest were high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6). Secondary outcomes included soluble tumor necrosis factor-alpha receptor 2 (sTNFαR2) and CTCs, while ctDNA served as an exploratory endpoint.

In the full cohort, exercise did not produce statistically significant changes in any of the primary or secondary biomarkers:

• hs-CRP increased by 20.9% relative to control (p = 0.32)
• IL-6 increased by 11.4% (p = 0.25)
• No significant changes were observed in sTNFαR2, TNF-α, or soluble IL-6 receptor
• CTC counts and ctDNA tumor fraction also showed no significant between-group differences

Subgroup and Exploratory Findings

Among the participants with elevated baseline hs-CRP (defined as ≥2 mg/L), aerobic exercise reduced hs-CRP by 35.5% compared to control (p = 0.031). In exploratory analyses limited to the exercise group, greater adherence to the aerobic exercise protocol was associated with reductions in CTCs (Spearman r = –0.37, p = 0.013).

These findings indicate that participants with higher baseline inflammation may be more responsive to exercise, and that consistent adherence may be necessary to observe tumor-related biomarker changes.

Safety and Feasibility

The intervention was well tolerated. There were no grade 3 or higher adverse events related to exercise or study procedures. Minor musculoskeletal complaints occurred in a small number of participants and resolved without medical intervention. Retention was high, with 98% of participants completing the 12-week endpoint assessment.

Study Limitations

The study population was younger, more often female, and more likely to be White than the broader CRC survivor population, which may limit generalizability. Although adherence was high, the 150 minute per week target for exercise was not fully achieved, and the sample size limited the ability to assess effect modification by cancer type, treatment history, comorbidities, or medication use.

Implications for Clinical Practice

This study demonstrates that high adherence to home-based aerobic exercise is feasible and may improve fitness capacity and physical activity in CRC survivors. Although no group-level changes in inflammation or liquid biopsy-derived tumor biomarkers were observed, subgroup and adherence-related findings suggest potentially greater benefit among individuals with elevated baseline inflammation or high engagement.

For clinicians, the results support the safety and utility of recommending moderate aerobic activity to CRC survivors. However, the biological effects of exercise may be more nuanced, possibly requiring longer intervention durations, higher exercise volumes, or targeting specific risk profiles.

Reference
Brown JC, Compton SLE, Kang A, et al. Effects of exercise on inflammation, circulating tumor cells, and circulating tumor DNA in colorectal cancer. J Sport Health Sci. 2025;14:101036. doi:10.1016/j.jshs.2025.101036