Efficacy and safety of adjuvant targeted therapy plus immunotherapy in hepatocellular carcinoma patients with high-risk recurrence factors after hepatectomy.

Hepatocellular carcinoma (HCC) has postoperative recurrence rates reaching 70% at five years in high-risk patients. Despite advances in surgical technique, effective adjuvant strategies for patients undergoing radical hepatectomy remain limited. This study aimed to evaluate adjuvant tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) in HCC patients with high-risk recurrence factors after hepatectomy. We retrospectively analyzed 312 HCC patients with high-risk factors who underwent radical hepatectomy between January 2019 and December 2023. Patients were divided into an adjuvant group (n = 68) receiving TKIs plus ICIs and a control group (n = 244). Propensity score matching at a 1:2 ratio was applied. The primary endpoint was recurrence-free survival (RFS). After matching, 156 patients were included (52 adjuvant, 104 control). The median RFS was 31.8 months in the adjuvant group versus 17.2 months in the control group (P = 0.003). Adjuvant therapy was an independent protective factor for RFS (HR = 0.61, 95% CI 0.41-0.91, P = 0.014) and overall survival (HR = 0.70, 95% CI 0.52-0.95, P = 0.023). Patients with multiple tumors, maximum tumor diameter > 5 cm, microvascular invasion, and portal vein tumor thrombus showed potential differential RFS benefit. Grade ≥ 3 adverse events totaled 11 events (16%), with no grade 4 or 5 events. Postoperative adjuvant TKI plus ICI therapy significantly prolonged RFS with acceptable safety in HCC patients with high-risk recurrence factors.