Efficacy and safety of systemic induction therapy in initially unresectable locally advanced intrahepatic and perihilar cholangiocarcinoma: A systematic review

Background: According to international guidelines, induction therapy may be considered in selected patients with initially unresectable locally advanced cholangiocarcinoma. The criteria for (un)resectability in cholangiocarcinoma varies between studies and no consensus-based agreement is available about these criteria. By performing a systematic literature review, we aimed to investigate the efficacy and safety of systemic induction therapy in initially unresectable locally advanced perihilar (pCCA) and intrahepatic cholangiocarcinoma (iCCA) and summarize resectability criteria used across studies. Methods: A literature search was performed in PubMed, EMBASE, Web of Science and Cochrane library to identify studies on systemic induction therapy in locally advanced pCCA and/or iCCA. The primary outcome was resection rate (RR) after induction therapy and secondary outcomes were overall survival (OS) and objective response rate (ORR). Results: Ten studies with a total of 1167 patients met the inclusion criteria and were included in this review. Among these patients, 334 (28.6%) were treated with systemic induction therapy. Across the studies, different types of chemotherapy regimens were administered (e.g., gemcitabine (based) chemotherapy and 5-FU (based) chemotherapy). Only six studies provided sufficient data and were used to analyze pooled (radical) resection rates. After induction therapy, 94 patients (39.2%) underwent a resection, of which R0 resections (22.9%). Pooled data on OS showed, better OS for chemotherapy plus resection versus chemotherapy only (pooled HR = 0.31, 95% CI = 0.19–0.50; P value < 0.0001). Conclusion: Adequately selected patients with locally advanced pCCA or iCCA may benefit from induction therapy followed by surgical resection. Prospective randomized controlled trials are warranted.