Surgical resection and survival in second primary intrahepatic cholangiocarcinoma: a population-based cohort study

Abstract Second primary intrahepatic cholangiocarcinoma (SP-ICC) represents a growing clinical challenge in the era of improved cancer survivorship. The survival impact of formal surgical resection in this population remains unclear. This study aimed to evaluate the association between surgical resection and survival outcomes in patients with SP-ICC. We conducted a population-based cohort study using the Surveillance, Epidemiology, and End Results database (2000–2022). Patients with SP-ICC were stratified by cancer-directed surgical resection status. Propensity score matching (1:1) was performed to balance baseline characteristics. Overall survival (OS) and cancer-specific survival (CSS) were assessed using Kaplan–Meier analysis and multivariable Cox regression models. Multiple Imputation by Chained Equations (MICE), competing risk analysis (Fine–Gray), and inverse probability of treatment weighting (IPTW) were performed as sensitivity analyses. Among 2,871 eligible patients, 702 (24.5%) underwent surgical resection. Younger age, earlier stage, and smaller tumor size were independent predictors for receiving surgery. After matching, 1,294 patients (647 per group) were included. In the matched cohort, median OS was 42.0 months (95% CI, 37.0–47.0) in the surgery group versus 9.0 months (95% CI, 8.0–10.0) in the non-surgery group ( P < 0.001). Surgical resection was independently associated with improved OS (adjusted hazard ratio [aHR], 0.27; 95% CI, 0.22–0.32; P < 0.001) and reduced cancer-specific mortality (adjusted subdistribution HR [aSHR], 0.40; 95% CI, 0.34–0.49; P < 0.001). These results remained robust across landmark, MICE (aHR, 0.30; 95% CI, 0.27–0.34), IPTW, and subgroup analyses. In this population-based study incorporating rigorous causal adjustment, surgical resection was independently associated with substantially prolonged survival in patients with SP-ICC. Conventional tumor stage and grade remained primary prognostic determinants, supporting careful multidisciplinary evaluation for surgical candidacy in this population.