Hepatic Artery Infusion Chemotherapy for Cholangiocarcinoma in 2025.

Background: Cholangiocarcinoma (CCA), particularly intrahepatic CCA (iCCA), is an aggressive hepatobiliary malignancy with limited therapeutic options and poor prognosis. For unresectable or advanced disease, systemic chemotherapy (SC) with gemcitabine plus cisplatin (GC) has long been the standard of care, and the recent addition of durvalumab to GC has become first-line therapy. However, median overall survival remains approximately ∼1 year, underscoring the need for more effective strategies. Summary: Hepatic arterial infusion chemotherapy (HAIC) has emerged as a promising locoregional approach, leveraging the liver's dual blood supply to deliver high local concentrations of cytotoxic agents while minimizing systemic toxicity. Advances in interventional techniques and chemotherapy protocols have expanded its role, positioning HAIC both as an alternative to SC and as a synergistic partner in multimodal regimens that include targeted therapy and immunotherapy. Importantly, the National Comprehensive Cancer Network (NCCN) now incorporates HAIC as a treatment option for select patients with unresectable iCCA, further endorsing its clinical utility. This integration underscores HAICs evolving role in multimodal therapy, where it can complement other treatment modalities to improve patient outcomes. This review synthesizes recent developments in HAIC for CCA, with emphasis on iCCA. It compares HAIC with SC, explores its integration into multimodal strategies, examines its role within the local treatment paradigm, and addresses clinical challenges such as technical precision, toxicity management, and the need for standardization. Finally, future directions - including biomarker-guided therapy, liquid biopsy, and advanced imaging - are discussed. Collectively, HAIC represents both a clinically relevant treatment option and a platform for precision oncology in CCA. Key Messages: (1) HAIC has emerged as a clinically validated and guidelines-supported treatment option that offers superior locoregional control for unresectable iCCA compared to SC alone. (2) The future of iCCA management lies in multimodal integration, where HAIC serves as a foundational platform that can be combined with systemic agents to achieve synergistic antitumor effects. (3) Transitioning from a "one-size-fits-all" approach to a precision oncology framework - incorporating molecular profiling and advanced imaging - is essential for refining patient selection and maximizing the survival benefits of HAIC-based strategies.