Conversion and Neoadjuvant Therapy for Intrahepatic Cholangiocarcinoma: Integrating Precision Medicine to Redefine Surgical Curability

Intrahepatic cholangiocarcinoma (ICC) is a type of primary liver cancer that is highly aggressive. In recent years, its incidence has continued to increase around the globe, yet outcomes remain poor and stagnant. Although surgical resection is the only treatment option capable of curing the cancer, most patients present with either advanced disease or unresectable tumors. Over the past decade, our understanding of ICC biology has evolved rapidly, with improved molecular classification and the clinical introduction of targeted therapies and immunotherapies. As a result of these advances, neoadjuvant, conversion, and downstaging strategies have been developed to redefine resectability and improve long‑term survival. Patients with selected tumors achieve good control with locoregional approaches, such as transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), and radiotherapy. At the same time, the routine use of next-generation sequencing (NGS) has allowed for personalized treatment of tumors with fibroblast growth factor receptor 2 gene (FGFR2) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, and immunogenic profiles. Even though procedures have come a long way, challenges remain. Treatment protocols differ from one institution to another, and criteria for what constitutes “biological resectability” are not standardized. High-quality prospective evidence exists but is nevertheless limited. As such, it is still unclear when the optimal timing for surgery is after systemic or locoregional therapy. This review focuses on the currently available clinical, molecular, and surgical aspects of intrahepatic cholangiocarcinoma to propose a precision-multimodal treatment algorithm.