Locoregional therapy combined with targeted therapy and immunotherapy for hepatocellular carcinoma with portal vein tumor thrombosis: a systematic review and meta-analysis

Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) represents a challenging clinical scenario with poor prognosis. This study aimed to evaluate the efficacy and safety of combining locoregional therapy with targeted therapy and immunotherapy (triple therapy) in unresectable HCC with PVTT. We conducted a Bayesian network meta-analysis of ten studies involving 1,241 HCC-PVTT patients, comparing triple therapy with targeted therapy plus immunotherapy in terms of overall survival (OS), progression-free survival (PFS), tumor response, and treatment-related adverse events. The results demonstrated that triple therapy significantly improved OS and PFS compared to targeted therapy plus immunotherapy alone. For OS, hepatic arterial infusion chemotherapy (HAIC)-based combination showed the greatest benefit (HR 0.48, 95% CI 0.32-0.74), followed by radiotherapy-based (HR 0.53, 95% CI 0.30-0.91) and transarterial chemoembolization-based combinations (HR 0.65, 95% CI 0.45-0.94). For PFS, radiotherapy-based triple therapy demonstrated the most pronounced benefit (HR 0.43, 95% CI 0.30-0.63), followed by HAIC-based combination (HR 0.49, 95% CI 0.34-0.72). While the addition of locoregional therapies increased the incidence of grade 3-4 adverse events (73.5% vs. 39.4%, p < 0.001), the safety profile remained clinically manageable. In conclusion, triple combination therapies represent a promising approach for unresectable HCC with PVTT that requires validation through large-scale randomized controlled trials to establish optimal treatment regimens.