SIRT or TACE in combination with lenvatinib and PD-(L)1 inhibitor in high-tumor burden hepatocellular carcinoma: a multicenter, retrospective, propensity score-matched study

Background: The combination of transarterial chemoembolization (TACE), lenvatinib, and PD-(L)1 inhibitors (TACE-L-P) has shown improved outcomes in hepatocellular carcinoma (HCC). This study aims to compare the efficacy and safety of selective internal radiation therapy (SIRT) plus lenvatinib and PD-(L)1 inhibitors (SIRT-L-P) versus TACE-L-P in Chinese HCC patients with high-tumor burden. Materials and Methods: This retrospective, multicenter, propensity score-matched study included HCC patients, beyond up-to-seven criteria or with portal vein tumor thrombus, treated with SIRT-L-P or TACE-L-P across four Chinese centers (2022–2024). Study endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety. Results: A total of 234 patients were included (109 in SIRT-L-P, 125 in TACE-L-P). After matching, 91 patients per group remained with well-balanced baseline characteristics. SIRT-L-P demonstrated significantly improved median PFS (12.1 vs. 9.0 months; HR 0.647, P = 0.021), OS (2-year OS rate 68.9% vs. 39.1%; HR 0.517, P = 0.014), and ORR (78.0% vs. 61.5% by mRECIST, P = 0.017; 56.0% vs. 35.2% by RECIST 1.1, P = 0.005) compared to TACE-L-P. Safety outcomes showed a lower overall incidence of adverse events (AEs) in the SIRT-L-P group compared to TACE-L-P (any grade: 83.5% vs. 95.6%, P = 0.008), while grade 3 AE rates were not significantly different (24.2% vs. 30.8%, P = 0.319). In a subset of patients receiving SIRT-L-P, risk tier combining post-SIRT neutrophil–lymphocyte ratio and peripheral CD8+ T-cell proportion was an independent predictor for PFS and OS. Conclusion: This study provides the first real-world evidence indicating that SIRT-L-P significantly improves efficacy and safety compared to TACE-L-P in high-tumor burden HCC.