Pre-transplant downstaging strategies for hepatocellular carcinoma with portal vein tumor thrombus: Current therapies and future challenges

Abstract

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, with approximately 35%-50% of patients presenting concurrent portal vein tumor thrombus (PVTT). Untreated HCC patients with PVTT have a median survival of only 2.5-4 months, posing significant challenges to liver transplantation outcomes. Downstaging therapies play a pivotal role in improving transplant eligibility rates and optimizing post-transplant outcomes. This systematic review summarizes current downstaging therapies, including transarterial chemoembolization, transarterial radioembolization, proton beam therapy, intraportal radiofrequency ablation, and other novel systemic modalities. In-depth analysis of their clinical applications, efficacy, and safety profiles were performed. Furthermore, the review critically evaluates future challenges, including optimized downstaging criteria, personalized and precision medicine approaches, and novel biomaterials for localized therapy for downstaged HCC patients. This review provides comprehensive theoretical and practical insights into pre-transplant downstaging for HCC with PVTT, while highlighting critical avenues for future research and clinical decision-making.

Keywords: Hepatocellular carcinoma; Portal vein tumor thrombus; Liver transplantation; Downstaging therapy; Transarterial chemoembolization

Core Tip: Hepatocellular carcinoma with portal vein tumor thrombus has long been considered a contraindication for liver transplantation due to poor prognosis. However, evolving downstaging strategies, including transarterial chemoembolization, transarterial radioembolization, proton beam therapy, and combination immunotherapies, have shown potential to convert select patients into transplant candidates. This review summarizes current clinical evidence and highlights future directions involving personalized medicine, novel biomaterials, and standardized criteria.