Recent advances in conversion therapy for hepatocellular carcinoma with portal vein tumor thrombosis.

Abstract

Portal vein tumor thrombosis (PVTT) is one of the most clinically consequential manifestations of advanced hepatocellular carcinoma (HCC). It reflects aggressive tumor biology, compromises portal venous inflow, and reduces the therapeutic window for locoregional intervention. Historically, macroscopic portal vein invasion generally placed patients within advanced-stage treatment pathways, in which systemic therapy constituted the standard treatment backbone and curative-intent approaches were applicable only to selected patients. This paradigm has now shifted. In recent years, the management of unresectable HCC has been reshaped by immune-based systemic therapy, more active tyrosine kinase inhibitor-based combinations, hepatic arterial infusion chemotherapy (HAIC), selective transarterial therapies, thrombus-directed radiotherapy, and increasingly standardized multidisciplinary conversion strategies. Consequently, a subset of patients with liver-dominant HCC and PVTT can now be downstaged to radical resection or other definitive local treatment, particularly when liver function is preserved and therapy is initiated before irreversible hepatic decompensation develops. This review summarizes recent advances in the diagnosis and classification of PVTT, the biological and technical rationale for conversion therapy, and the evolving evidence for systemic therapy, HAIC, transarterial chemoembolization (TACE), radiotherapy, triple-modality treatment, salvage surgery, and postoperative management. It also highlights key limitations, including the predominance of retrospective East Asian cohorts, heterogeneity in PVTT classification and treatment protocols, uncertainty regarding the optimal timing of surgery, and the absence of validated biomarkers for selecting patients most likely to benefit from aggressive multimodality treatment. Overall, the available evidence supports integrating response-guided multidisciplinary strategies into established evidence-based treatment frameworks for carefully selected patients. Even so, conversion therapy for HCC with PVTT remains an evidence-evolving strategy that should be applied with careful patient selection, disciplined treatment sequencing, and substantial institutional expertise rather than adopted as a universal standard of care.