Integrating locoregional therapy with systemic and emerging cellular therapies in advanced intrahepatic...

Advanced intrahepatic cholangiocarcinoma (ICC) may be liver-confined or liver-dominant after curative resection is no longer feasible. This distribution supports a role for locoregional therapy (LRT), whereas occult or established extrahepatic disease still requires systemic control. This narrative review integrates the most recent clinical and mechanistic evidence for combining LRT with chemotherapy, immune checkpoint inhibition, molecularly targeted treatment, and cellular therapy. Randomized phase III biliary tract cancer trials support gemcitabine-cisplatin plus durvalumab or pembrolizumab as first-line systemic therapy, but the primary analyses improved median overall survival by only 1.3 and 1.8 months. Evidence for adding LRT is less mature and heterogeneous. Prospective single-arm studies of yttrium-90 radioembolization, hepatic arterial infusion, radiotherapy, and cryoablation-based combinations report activity in selected ICC populations, but most lack a contemporary control and cannot isolate the contribution of LRT. No biomarker has validated the incremental benefit of a specific LRT. Clinical development should therefore specify the LRT modality and exposure, disease distribution, systemic backbone, treatment intent, and safety boundary. Routine adoption requires reproducible protocols, comparative survival and safety endpoints, and paired biomarker collection.