Sequential surgery following conversion therapy based on combination of immune checkpoint inhibitors and antiangiogenic targeted drugs as a potential approach for advanced hepatocellular carcinoma with portal vein tumor thrombus: a prospective study

Background: Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) face a very poor prognosis. And it remains unclear whether sequential surgery following conversion therapy based on immunotherapy combined with targeted therapy can yield long‑term survival benefits. This study aims to evaluate the long-term efficacy and safety of hepatocellular carcinoma patients with portal vein tumor thrombus receiving sequential surgery following conversion therapy with a combination of targeted therapy and immunotherapy, thereby demonstrating the therapeutic potential of this regimen. Methods: Data from 76 HCC patients with PVTT treated with programmed death-1 (PD-1) inhibitors and tyrosine kinase inhibitors (TKIs) followed by surgical treatment at Chinese People's Liberation Army General Hospital (June 2019 to June 2024) were analyzed. Recurrence-free survival (RFS) and overall survival (OS) were primary endpoints. Results: The median RFS was 21 months; the median OS was 62 months. RFS rates at 6 months, 1 year, 2 years, and 3 years were 76.2%, 59.7%, 48.1%, and 42.5%, respectively. OS rates at 6 months, 1 year, 2 years, 3 years, and 5 years were 98.7%, 93.4%, 78.1%, 72.4%, and 45.5%, respectively. Cox regression showed that preoperative alpha-fetoprotein (AFP) ≥20 ng/mL was an independent mortality factor, while non-major-pathological-response (non-mPR) and tumor size >50 mm were independent recurrence factors. Adverse events and surgical complications were evaluated, with no patient deaths resulting from conversion therapy or sequential radical surgery. Conclusions: For HCC patients with PVTT who achieve successful conversion and undergo radical surgery, sequential surgery following conversion therapy based on combination of immune checkpoint inhibitors (ICIs) and anti-angiogenic targeted drugs (AATDs) is associated with favorable RFS and OS, and appears safe and effective. These findings suggest that this regimen may represent a promising option for these patients.