2026 Volume 20 Issue 4 Pages 348-360
Cholangiocarcinoma (CCA) is a highly aggressive, molecularly heterogeneous biliary tract malignancy and the second most common primary liver cancer, and it has an increasing global incidence and persistently poor prognosis. Recent updates of international guidelines, including those from the NCCN, ESMO, EASL, CSCO, BSG, and Japanese societies, along with rapid advances in precision oncology, have substantially changed the clinical management of CCA. This review systematically compares current global guidelines, highlighting both areas of consensus and regional differences in epidemiology, risk factors, screening strategies, diagnostic approaches, pathological and molecular classification, staging systems, surgical indications, systemic therapy, and multidisciplinary management. This review also summarizes recent advances in molecular diagnostics, including next-generation sequencing, liquid biopsy, circulating tumor DNA, extracellular vesicles, artificial intelligence-assisted imaging, radiomics, and emerging prognostic biomarkers. The evolving roles of immune checkpoint inhibitors, molecularly targeted therapies against FGFR2, IDH1, HER2, BRAF, NTRK, and MSI-H/dMMR, liver transplantation, locoregional treatment, and conversion (translational) therapy are also discussed. Finally, this review addresses current challenges, including drug resistance, limited access to molecular testing, regional disparities in healthcare resources, and the lack of universally accepted screening strategies. By integrating updated guideline recommendations with the latest clinical evidence, this review provides a comprehensive reference for evidence-based clinical decision-making and future translational research in CCA.
