Benefiting Subgroup From Adjuvant Chemotherapy in Intrahepatic Cholangiocarcinoma: A Propensity Score‐Matched Study

ABSTRACT

The survival benefit of adjuvant chemotherapy (ACT) following resection of intrahepatic cholangiocarcinoma (iCCA) remains controversial; moreover, the patient group that could benefit most from this approach remains undetermined. We conducted a retrospective cohort study of 423 patients (median age 65 years; 52.2% male; 297 patients who received ACT) who underwent curative intent resection of iCCA between 2021 and 2024. To minimize selection bias, propensity score matching (PSM) at a 2:1 ratio was performed. Overall survival (OS) was the primary end point. Survival analyses were conducted using Kaplan–Meier and Cox regression methods. In the PSM‐matched cohort, ACT significantly improved OS compared to observation alone (hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.32–0.82, p  = 0.005). Subgroup analyses revealed marked heterogeneity in treatment effect. The most remarkable finding was a strong interaction between treatment and histological subtype ( p for interaction = 0.041). Patients with small‐duct type iCCA derived a substantial survival benefit from ACT (HR = 0.33, 95% CI: 0.17–0.63, p  = 0.001). In contrast, patients with large‐duct type iCCA did not show a significant OS benefit (HR = 0.89, 95% CI: 0.45–1.76, p  = 0.737). In conclusion, postoperative ACT was associated with improved OS after resection of iCCA. Exploratory interaction analyses suggested that the magnitude of this association may differ according to histological subtype, with a more pronounced survival benefit observed in patients with small‐duct type iCCA. These findings should be considered hypothesis‐generating and require confirmation in independent prospective cohorts before histological subtype can be incorporated into treatment‐selection strategies.