Current Status of Multidisciplinary Treatment Strategies for Hepatocellular Carcinoma in the Era of Advanced Systemic Therapies

The therapeutic landscape of hepatocellular carcinoma (HCC) has been transformed by recent advancements in systemic therapies, particularly with the introduction of immune checkpoint inhibitors, expanding treatment options beyond conventional locoregional approaches. This review provides an overview of evidence accumulated from recent Phase III trials of first-line regimens and key second-line agents and examines how these advances enable multidisciplinary treatment strategies and timely transition to curative local treatments. We highlight prospective and retrospective data on systemic therapy administered in combination with or in sequence with locoregional treatment modalities, including TACE-based combinations and "conversion" concepts leading to resection. A central focus is the oncological resectability criteria proposed by the Japan Liver Cancer Association and the Japanese Society of Hepato-Biliary-Pancreatic Surgery, which provide an objective framework to assess surgical indications under contemporary systemic therapy. Validation studies have consistently demonstrated robust prognostic stratification across resectable (R), borderline resectable 1 (BR1), and borderline resectable 2 (BR2) categories. Evidence for application of the oncological resectability criteria in treatment decision-making is still insufficient. Thus, future prospective studies and real-world registries aligned with the resectability framework are essential for defining the optimal timing, sequencing, and candidacy for surgery to ultimately enable provision of individualized, evidence-based care for patients with advanced HCC.