The Efficacy and Safety of Combined Locoregional and Systemic Therapy versus Systemic Therapy Alone in Patients with Hepatocellular Carcinoma and Portal Vein Tumor Thrombosis: A Multicenter Real-World Retrospective Cohort Study
Abstract
Background To compare the efficacy and safety of combined locoregional and systemic therapy vs systemic therapy alone in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT). Methods This multicenter retrospective study included 337 patients with HCC and PVTT who received systemic therapy alone (n=121) or combined locoregional and systemic therapy (n=216). Propensity score matching (PSM) was performed to reduce baseline imbalances. Overall survival (OS), progression-free survival (PFS), tumor response and adverse events (AEs) were compared. When the proportional hazards assumption was violated, time-varying Cox and restricted mean survival time (RMST) analyses were performed. Results In the whole cohort, combined therapy was associated with a lower hazard of death (hazard ratio [HR]=0.57, 95% confidence interval [CI]=0.38–0.86, P=0.007), and this association remained after PSM (HR=0.54, 95% CI=0.34–0.86, P=0.009). Conventional Kaplan–Meier analysis did not show a significant PFS difference after PSM (median PFS, 12.97 vs 10.20 months; P=0.394); however, the proportional hazards assumption for PFS was violated. RMST analyses showed significant cumulative PFS advantages favoring combined therapy at 12 months (+1.48 months; P=0.008) and 16 months (+1.69 months; P=0.010). After PSM, the objective response rate according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) was higher with combined therapy (61.1% vs 45.4%, P=0.029). In patients with Vp3–4 PVTT, combined therapy was associated with a lower hazard of death (HR=0.60, 95% CI=0.39–0.93, P=0.023). Grade 3–4 AEs were comparable between groups (29.2% vs 31.4%, P=0.759). Conclusion Combined locoregional and systemic therapy was associated with longer OS and an early, time-dependent PFS advantage compared with systemic therapy alone in patients with HCC and PVTT, with a more apparent OS benefit signal in Vp3–4 disease and no clear increase in grade 3–4 AEs.