Expanding the path to cure - a narrative review on optimizing multimodality sequencing in HCC

Advances in hepatocellular carcinoma (HCC) treatment and patient profiling are driving a shift toward personalized, multimodality management. The enhanced efficacy of locoregional therapies (LRTs) and systemic regimens has expanded treatment options across palliative and curative settings. For patients eligible to curative-intent treatment, adjunctive approaches aim to enhance procedural feasibility and optimize patient outcomes. Bridging and downstaging to liver transplantation, while traditionally relying on intra-arterial therapies are now seeing emerging alternatives such as stereotactic body radiotherapy (SBRT) and systemic agents. In the perioperative setting, immune checkpoint inhibitor (ICI)-based regimens have shown robust pathological response rates and have significantly improved major pathological response and event-free survival for intermediate- to high-risk resectable patients in a recent phase III trial. For incurable disease, treatment intensification via multimodal combinations improves anti-tumor efficacy. Adding ICI-antiangiogenic regimens to transarterial chemoembolization has demonstrated improved response rates and progression-free survival in multiple phase III trials. Systemic-LRT combinations are also being explored in advanced HCC, with a recent phase III trial indicating SBRT's efficacy in this setting. Notably, curative conversion approaches are emerging to enable subsequent curative-intent treatment in select patients that were previously considered incurable. While multimodal care offers significant promise, its complexity necessitates a multidisciplinary approach to patient and treatment selection, and toxicity management. With multidisciplinary guidance, multimodality approaches promise to expand the path to cure for an increasing number of HCC patients.