Transarterial Chemoembolization Combined with PD-1 Inhibitors and TKIs for Intermediate - to - Advanced Hepatocellular Carcinoma: Efficacy and Progress in Conversion Resection

Abstract

Objective: To review the mechanisms, efficacy, and progress in conversion resection of transarterial chemoembolization (TACE) combined with programmed death-1 (PD-1) inhibitors and tyrosine kinase inhibitors (TKIs) in intermediate-to-advanced hepatocellular carcinoma (HCC). Methods: PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP were searched from inception to 2025, focusing on studies published within the past five years, using terms including “hepatocellular carcinoma,” “transarterial chemoembolization,” “PD-1 inhibitor,” “tyrosine kinase inhibitor,” “conversion therapy,” and “conversion resection.” Evidence was integrated narratively. Results: Mechanistically, ischemia and locoregional immune microenvironment remodeling induced by TACE, immune activation by PD-1 inhibitors, and the anti-angiogenic and immunomodulatory effects of TKIs together constitute a multilayered “locoregional + systemic” synergy. In terms of efficacy, the triple regimen showed higher objective response rate (ORR), prolonged progression-free survival (PFS), and overall survival (OS) than dual therapy or TACE alone in most studies. With respect to conversion resection, reported rates varied widely because of inconsistent endpoint definitions: prospective studies, which mostly used actual completion of surgery as the endpoint, generally reported higher values, whereas retrospective studies, which mostly used meeting resectability criteria or entry into the surgical pathway as the endpoint, generally reported lower values; the two are not directly comparable. The survival benefit after conversion resection was relatively consistent across studies. Predictors of successful conversion included early tumor response, magnitude of alpha-fetoprotein (AFP) decline, decreased 18F-FDG uptake, and immune microenvironment biomarkers, but most remain exploratory. Conclusion: TACE combined with PD-1 inhibitors and TKIs has shown the potential to convert some intermediate-to-advanced HCC into a curable state and may broaden the population eligible for curative treatment. However, current evidence is dominated by retrospective and single-arm studies, and standardized conversion resection criteria, precise patient selection, and prospective randomized validation remain to be addressed. These conclusions represent promising exploratory evidence rather than a definitive conclusion.