BACKGROUND: The biological mechanisms by which postdiagnosis physical activity improves disease-free survival in colorectal cancer survivors remain incompletely understood. This trial tested the hypothesis that 12 wk of moderate-intensity aerobic exercise, when compared with a control group, would change inflammation, CTCs, and ctDNA in a manner consistent with an improved cancer prognosis. METHODS: This trial randomized Stages I to III colorectal cancer survivors to 12 wk of home-based moderate-intensity aerobic exercise or a waitlist control group. The co-primary endpoints were high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6), secondary endpoints were soluble tumor necrosis factor-alpha receptor 2 (sTNFalphaR2) and circulating tumor cells (CTCs), and the exploratory endpoint was tumor fraction quantified from circulating tumor DNA. RESULTS: Sixty subjects were randomized (age 60.6 +/- 10.8 years, mean +/- SD; 39 (65%) females; 46 (77%) colonic primary tumor), and 59 (98%) subjects completed the study. Over 12 wk, exercise adherence was 92% (95% confidence interval (95% CI) 86 to 99). Exercise improved submaximal fitness capacity (0.36 metabolic equivalents; 95% CI 0.05 to 0.67; p = 0.025) and objectively measured moderate-to-vigorous-intensity physical activity (34.8%, 95% CI 11.3 to 63.1; p = 0.002) compared to control. Exercise did not change hs-CRP (20.9%, 95% CI -17.1 to 76.2; p = 0.32), IL-6 (11.4%, 95% CI -7.5 to 34.0; p = 0.25), or sTNFalphaR2 (-3.6%, 95% CI -13.7 to 7.7; p = 0.52) compared to control. In the subgroup of subjects with elevated baseline hs-CRP (n = 35, 58.3%), aerobic exercise reduced hs-CRP (-35.5%, 95% CI -55.3 to -3.8; p = 0.031). Exercise did not change CTCs (0.59 cells/mL, 95% CI -0.33 to 1.51; p = 0.21) or tumor fraction (0.0005, 95% CI -0.0024 to 0.0034; p = 0.73). In exploratory analyses, higher aerobic exercise adherence correlated with a reduction in CTCs (rho -0.37, 95% CI -0.66 to -0.08; p = 0.013). CONCLUSION: Colorectal cancer survivors achieved high adherence to a home-based moderate-intensity aerobic exercise prescription that improved fitness capacity and physical activity but did not reduce inflammation or change tumor endpoints from a liquid biopsy.

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