Body Mass Index at Diagnosis, Prediagnostic Weight Loss, and Survival in Colorectal Cancer

Evidence on the association of excess adiposity with colorectal cancer (CRC) prognosis is conflicting, with some studies reporting better survival in patients with elevated body mass index (BMI)-often referred to as the obesity paradox.

To investigate to what extent the obesity paradox can be explained by prediagnostic cancer-associated weight loss.

This multicenter, population-based case-control study with prospective follow-up included patients aged 30 years or older with histologically confirmed CRC who were recruited from more than 20 hospitals in southwest Germany between 2001 and 2016, with survival follow-up through September 2018. Analysis was conducted from September 2025 to June 2026.

BMI at diagnosis (underweight, BMI <18.5; normal weight, BMI 18.5 to <25.0; overweight, BMI 25.0 to <30.0; obesity, BMI ≥30.0), and percent weight change during the 5 to 14 years preceding diagnosis, both derived from self-reported height and body weight.

Overall, CRC-specific, and recurrence-free survival were assessed using Cox proportional hazards regression models adjusted for demographic and lifestyle factors, tumor characteristics, and comorbidities, estimated as hazard ratios (HRs) with 95% CIs.

Among 5521 patients with CRC (2159 female [39%]; median [IQR] age at diagnosis, 69 [61-76] years), 2429 deaths occurred during a median (IQR) follow-up of 5.2 (3.4-9.9) years, including 1381 CRC-related deaths. Compared with patients with normal weight at diagnosis, those who had overweight had modestly higher overall survival (HR, 0.89; 95% CI, 0.81-0.98), while no association was observed for obesity. Prediagnostic weight loss of more than 10% was associated with worse survival (HR, 1.55; 95% CI, 1.39-1.72). Upon mutual adjustment for at-diagnosis BMI and prediagnostic weight change, associations for overweight and obesity were attenuated to null.

In this case-control study with prospective follow-up of patients with CRC, the obesity paradox appeared to be largely attributable to prediagnostic cancer-associated weight loss. The apparent survival advantage associated with overweight and obesity at diagnosis should not be interpreted as evidence to encourage weight gain for patients with healthy weight or to revise existing survivorship recommendations.