Explaining the Obesity Paradox: The Association between Body Composition and Colorectal Cancer Survival (C-SCANS Study).

Body composition may partially explain the U-shaped association between body mass index (BMI) and colorectal cancer survival. Muscle and adiposity at colorectal cancer diagnosis and survival were examined in a retrospective cohort using Kaplan-Meier curves, multivariable Cox regression, and restricted cubic splines in 3,262 early-stage (I-III) male (50%) and female (50%) patients. Sarcopenia was defined using optimal stratification and sex- and BMI-specific cut points. High adiposity was defined as the highest tertile of sex-specific total adipose tissue (TAT). Primary outcomes were overall mortality and colorectal cancer-specific mortality (CRCsM). Slightly over 42% patients were sarcopenic. During 5.8 years of follow-up, 788 deaths occurred, including 433 from colorectal cancer. Sarcopenic patients had a 27% [HR, 1.27; 95% confidence interval (CI), 1.09-1.48] higher risk of overall mortality than those who were not sarcopenic. Females with both low muscle and high adiposity had a 64% higher risk of overall mortality (HR, 1.64; 95% CI, 1.05-2.57) than females with adequate muscle and lower adiposity. The lowest risk of overall mortality was seen in patients with a BMI between 25 and <30 kg/m, a range associated with the greatest number of patients (58.6%) who were not at increased risk of overall mortality due to either low muscle or high adiposity. Sarcopenia is prevalent among patients with non-metastatic colorectal cancer, and should, along with adiposity be a standard oncological marker. Our findings suggest a biologic explanation for the obesity paradox in colorectal cancer and refute the notion that the association between overweight and lower mortality is due solely to methodologic biases. .