Differential Prognostic Impact of Prior Cholecystectomy Between Proximal and Distal Colorectal Cancer: A 12‐Year Retrospective Cohort Study of 3487 Consecutive Patients

ABSTRACT Background The prognostic impact of prior cholecystectomy (CCY) in patients with colorectal cancer (CRC) remains uncertain. The aim of this study was to evaluate the prognostic impact of prior CCY in a large cohort of patients with CRC, with particular attention to tumor location. Methods We retrospectively analyzed all patients diagnosed with colorectal adenocarcinoma between January 2012 and December 2023. Patients were classified into proximal (cecum, ascending, and transverse) and distal (descending, sigmoid, and rectum) groups. Survival outcomes were compared using multivariate Cox proportional hazards regression models, including an interaction term between tumor location and history of CCY. Propensity score matching (PSM) was performed as a sensitivity analysis. Results Among 3487 patients (1375 proximal and 2112 distal CRC), 158 (4.8%) had a history of CCY. Proximal CRC was more frequently associated with female sex, older age, history of CCY, poor differentiation, BRAF mutation, MSI‐high status, and non‐resection initial strategy ( p ≤ 0.005). Among proximal CRC patients, multivariate analysis revealed TNM stage III/IV ( p < 0.001), non‐resection initial strategy ( p < 0.001), and history of CCY ( p = 0.042) were independent predictors of poor overall survival (OS). Prior CCY was associated with worse OS in proximal CRC ( p = 0.004). A significant interaction between tumor location and history of CCY was observed ( p for interaction = 0.025). Conclusions History of CCY was associated with worse prognosis in proximal CRC but not in distal CRC, suggesting a differential impact of CCY on prognosis in CRC. Our findings would provide insight into further research on bile acid metabolism or microbiome modulation in CRC patients.