Effects of exercise on inflammation, circulating tumor cells, and circulating tumor DNA in colorectal cancer.

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 weeks of moderate-intensity aerobic exercise, when compared with a control group, would change inflammation, circulating tumor cells (CTCs), and circulating tumor DNA (ctDNA) in a manner consistent with an improved cancer prognosis.

Methods: This trial randomized Stages I-III colorectal cancer survivors to 12 weeks 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-α receptor 2 (sTNFαR2) and CTCs, and the exploratory endpoint was tumor fraction quantified from ctDNA.

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 weeks, exercise adherence was 92% (95% confidence interval (95%CI): 86‒99). Exercise improved submaximal fitness capacity (0.36 metabolic equivalents; 95%CI: 0.05‒0.67; p = 0.025) and objectively measured moderate-to-vigorous-intensity physical activity (34.8%, 95%CI: 11.3‒63.1; 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 sTNFαR2 (-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 (ρ = -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.