Synergistic era: practice and reflection on TACE combined with systemic therapy in hepatocellular carcinoma

The treatment paradigm for hepatocellular carcinoma (HCC) is evolving from traditional stage-based monotherapy toward a synergistic era characterized by the proactive integration of locoregional and systemic therapies. Transarterial chemoembolization (TACE) plus systemic therapy has shown notable synergistic potential, but it also complicates clinical decision-making and trial interpretation. This review briefly outlines advances in TACE and systemic therapy, summarizes key randomized controlled trials of combination therapy, and analyzes core challenges in treatment timing, TACE implementation, endpoint design, and patient selection. Although combination regimens have not consistently demonstrated significant overall survival (OS) benefits in intermediate-to-advanced HCC, improvements in progression-free survival, objective response rate, and other disease-control endpoints have been increasingly reported. Future prospective trials should look beyond drug selection alone and refine combination timing, clinically meaningful endpoints, TACE standardization, and subgroup selection. These refinements may help determine how early disease-control gains can be translated more consistently into durable OS benefit, particularly for patients with intermediate-stage HCC.