The use of locoregional therapies in cholangiocarcinoma

The standard of care for patients with unresectable or advanced cholangiocarcinoma (CCA) is systemic chemotherapy combined with immunotherapy, which achieves a median overall survival (OS) of 13 months and a 3-year OS of 15%. This provides the benchmark against which additional locoregional therapies are evaluated. This narrative literature review examined locoregional therapies, their clinical outcomes, and recommendations for their role in the management of patients with CCA. The review focused on intrahepatic (iCCA) and perihilar CCA (pCCA) with locoregional disease in patients who were ineligible for surgical resection. A literature search was conducted in PubMed (MEDLINE) to identify clinical studies evaluating locoregional therapies in CCA. Ongoing and completed trials were identified through ClinicalTrials.gov. For iCCA, clinical trials have evaluated percutaneous image-guided local ablative therapies, including radiofrequency ablation or microwave ablation (3-year OS 42%), cryoablation, interstitial electroporation, and brachytherapy. Other trials have analysed external beam radiotherapy (EBRT), often using high-precision techniques (3-year OS 38%), as well as intra-arterial therapies, including transarterial chemoembolisation (3-year OS 17%), selective internal radioembolisation (3-year OS 40%), and floxuridine delivery through a hepatic arterial infusion pump (3-year OS 26-50%). For pCCA, EBRT has been evaluated in three treatment settings: definitive therapy (1-year OS 100%), adjuvant postoperative therapy (3-year OS 58%), and neoadjuvant therapy before liver transplantation (3-year OS 62%). Recent and ongoing clinical trials demonstrate a clear trend toward combining locoregional and standard-of-care systemic therapies. Few randomised controlled trials have been conducted. Until further evidence from randomised controlled trials becomes available, treatment strategies for patients with unresectable or advanced CCA should be individualised, incorporating flexible, staged combinations of locoregional and systemic therapies within a personalised therapeutic framework. These decisions should be made within a multidisciplinary tumour board.