Combination of locoregional and systemic therapy for hepatocellular carcinoma with portal vein tumor thrombus: a real-world retrospective study.

[BACKGROUND] The optimal treatment strategy for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) remains undefined. Although combinations of locoregional therapies-such as transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC)-with systemic agents (tyrosine kinase inhibitors [TKIs] and PD-1 inhibitors) show promise, direct comparative evidence among different regimens remains limited.

[METHODS] In this single-center retrospective study, we included 347 patients with unresectable HCC and PVTT treated between January 2020 and December 2022. Patients were categorized into four groups based on initial therapy: TACE-HAIC-TP (n = 79), TACE-TP (n = 90), HAIC-TP (n = 98), and TACE alone (n = 80). The primary endpoints were overall survival (OS) and progression-free survival (PFS).

[RESULTS] All combination regimens significantly improved OS and PFS compared with TACE alone (median OS: 11.4 months; median PFS: 5.8 months; all p < 0.001). The TACE-HAIC-TP group had the longest median OS (21.0 months) and PFS (15.3 months). However, after propensity score matching, no significant difference in survival outcomes was observed between the TACE-HAIC-TP and HAIC-TP groups. The HAIC-TP and TACE-TP regimens demonstrated comparable efficacy. Regarding safety, TACE-HAIC-TP was associated with the highest incidence of adverse events, including appetite loss, fatigue, nausea/vomiting, bleeding, and immune-related pneumonia. HAIC-TP carried a higher risk of gastrointestinal reactions and bleeding, whereas hand-foot syndrome was more frequent with TACE-TP.

[CONCLUSION] In patients with unresectable HCC and PVTT, combining TKIs and PD-1 inhibitors with locoregional therapy (TACE or HAIC) confers superior survival benefits over TACE monotherapy. The HAIC-TP regimen was associated with a more favorable balance of efficacy and tolerability compared with the more intensive TACE-HAIC-TP strategy, suggesting it may represent a promising therapeutic option pending prospective validation. Treatment selection should be individualized based on efficacy-safety trade-offs.