[Effect of conversion therapy and prognostic factors in patients with advanced intrahepatic cholangiocarcinoma: a...

Objectives: To investigate the effect of gemcitabine plus cisplatin (GC) chemotherapy combined with immunotherapy in patients with unresectable intrahepatic cholangiocarcinoma (ICC) and its prognostic factors. Methods: This is a retrospective case series study. Data of 387 consecutive treatment-naive patients with unresectable ICC admitted to the Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital from May 2022 to May 2025 were retrospectively collected. All patients received GC regimen chemotherapy combined with immune checkpoint inhibitors. There were 260 males (67.2%) and 127 females (32.8%); the age was (54.4±10.3) years (range: 23 to 82 years). The primary study endpoints were overall survival (OS) time and progression-free survival (PFS) time, and the secondary endpoints were antitumor effects and adverse reactions. Intergroup comparisons were performed using independent sample t-test, Mann-Whitney U test, χ² test, or Fisher's exact probability method. The propensity score matching method was used to match the surgical patients and the non-surgical patients in a 1∶2 ratio, with a caliper value of 0.02. OS and PFS curves were plotted by Kaplan-Meier method, and prognostic factors for OS and PFS were analyzed using univariate and multivariate Cox regression models. Results: Among all patients,the final surgical conversion rate was 8.8% (34/387) and objective response rate was 36.2% (140/387), the median OS time was 16.67 months (95%CI: 14.80 to 17.79 months),and the median PFS time was 8.22 months (95%CI: 7.53 to 8.95 months). The survival time of the surgery group was better than that of the non-surgery group (median OS time: 22.86 months vs. 15.65 months, P=0.038; median PFS time: 13.68 months vs. 7.96 months, P=0.001). The overall incidence of adverse reactions was 98.4%, and the grade Ⅲ to Ⅳ adverse reaction rate was 72.4%. Univariate and multivariate analyses revealed that surgical intervention (HR=0.447, 95%CI: 0.219 to 0.909, P=0.026; HR=0.460, 95%CI: 0.265 to 0.796, P=0.006) was an independent protective factor for OS and PFS. After propensity score matching, multivariate analysis results further demonstrated that surgical intervention(HR=0.211, 95%CI: 0.095 to 0.467, P<0.01; HR=0.254, 95%CI: 0.132 to 0.487, P<0.01) remained an independent protective factor for OS and PFS. Conclusions: Chemotherapy combined with immunotherapy, as a first-line treatment regimen for patients with advanced ICC, has good antitumor effects and can improve patient prognosis without causing serious new adverse reactions. For patients who can undergo surgical resection after conversion and downstaging, radical surgical resection can improve prognosis compared to continuing systemic therapy.