Weighing the Odds: Body Mass Index and Recurrence-Free Survival in Early-Onset Colorectal Cancer

Background: Early-Onset Colorectal Cancer (EOCRC, < 50 years) is rising sharply in many parts of the world. The "obesity paradox", where overweight correlates with better outcome despite obesity being a risk factor, is established in colorectal cancer (CRC) overall but remains ambiguous in EOCRC. Aim: To investigate the association of Body Mass Index (BMI) at diagnosis and recurrence-free survival (RFS) in EOCRC and compare it to average-onset colorectal cancer (AOCRC, older than or equal to 50 years). Methods: A retrospective cohort study at Sahlgrenska University Hospital included 1,459 patients with curative-intent colorectal adenocarcinoma surgery comprising EOCRC (n=159) and AOCRC (n=1,300) cohorts. Cox proportional hazards models assessed the relation of BMI to RFS, adjusted for tumour stage, location, and differentiation. Restricted cubic splines were used to model BMI as a continuous variable, and model fit was assessed with likelihood-ratio tests (LRT). Results: In EOCRC, continuous BMI was significantly associated with RFS (LRT p=0.02), displaying a U-shaped association with the lowest hazard at BMI 27 and highest at BMI <20 and >30. In AOCRC continuous BMI was not associated with RFS (LRT p=0.15) and the spline curve was flat. An interaction analysis showed a significant difference between the cohorts (LRT p=0.046). Conclusion: Continuous BMI was significantly associated with RFS in EOCRC but not in AOCRC suggesting the "obesity paradox" may be specific to EOCRC. This may reflect differences in body composition, tumour biology and systemic metabolism between EOCRC and AOCRC or may be due to methodological biases. Future research should incorporate biomarkers, as well as refined measures of body composition.