Inflammation, Physical Activity, and Disease-Free Survival in Stage III Colon Cancer: CALGB/SWOG 80702 (Alliance)

Abstract Background Both inflammation and insufficient physical inactivity contribute to individual-level risk of disease recurrence and death in stage III colon cancer. The extent to which increased inflammatory risk can be offset by sufficient physical activity remains unknown. Methods This cohort study was nested within the CALGB/SWOG 80702 (Alliance) randomized trial. Inflammatory burden was quantified by high-sensitivity C-reactive protein, interleukin-6, and soluble tumor necrosis factor-α receptor 2 after recovery from tumor resection. Physical activity was measured during and after postoperative chemotherapy. The primary endpoint was disease-free survival. Results The 3-year disease-free survival rate was 88.4% among patients with low inflammation and sufficient physical activity (referent group for all comparisons), 84.9% with low inflammation and insufficient physical activity [absolute risk difference (RD): −3.5%, 95% Confidence Interval (CI): −11.3, 4.3; P = .38], 78.0% with intermediate inflammation and insufficient physical activity (RD: −10.4%, 95% CI: −17.4, −3.3; P = .007), and 79.7% with high inflammation and insufficient physical activity (RD: −8.7%, 95% CI: −15.7, −1.6; P = .022). In contrast, the 3-year disease-free survival rate was 87.3% among patients with intermediate inflammation and sufficient physical activity (RD: −1.1%, 95% CI: −7.5, 5.3; P = .74) and 84.4% with high inflammation and sufficient physical activity (RD: −4.0%, 95% CI: −12.3, 4.3; P = .34). Conclusion In this observational study of stage III colon cancer patients, physical activity was associated with improved disease-free survival despite high inflammation. Patients with intermediate or high inflammation who were physically active had disease-free survival rates that were not statistically significantly different from those with low inflammation.