Enhanced efficacy and long-term survival with SBRT plus PD-1 inhibitors versus SBRT alone in unresectable HCC: a multicenter PSM study

BACKGROUND: Radiotherapy (RT) provides meaningful local control for hepatocellular carcinoma (HCC) but is limited by radio-resistance. Preclinical and clinical data suggest that adding programmed death receptor-1 (PD-1) blockade may enhance radiosensitivity in various malignancies. We compared outcomes of stereotactic body radiotherapy (SBRT) plus PD-1 inhibitors vs SBRT alone in unresectable HCC. METHODS: We retrospectively analyzed consecutive patients treated with SBRT (January 2019-December 2024) from 3 centers. Key exclusions removed confounding from recent systemic/locoregional therapies. Propensity score matching (PSM, 1:1) balanced demographics, liver function, tumor characteristics, and prior therapy. Tumor responses were assessed by RECIST 1.1, while survival was estimated by Kaplan-Meier and Cox models. RESULTS: Of 540 eligible patients, 157 received RT+PD-1 and 383 received RT alone; after PSM, 314 patients remained (157/157). Median follow-up was 29.9 months (IQR 21-36). After matching, RT+PD-1 showed a higher objective response rate (ORR) that approached significance (48.4% vs 37.6%, P = .053). Progression-free survival (PFS) was significantly prolonged with RT+PD-1 (median 11.0 vs 8.5 months; 1-year 69.9% vs 54.1%; HR 0.75, 95% CI 0.58-0.96, P = .024). OS also favored RT+PD-1 (median 33.9 vs 26.3 months; 3-year 41.9% vs 23.0%; HR 0.74, 95% CI 0.54-1.02, P = .066). On multivariable analysis after PSM, RT+PD-1 independently reduced risks of progression (HR 0.69, P = .005) and death (HR 0.70, P = .029). Adverse events (AEs) were similar overall, but grade ≥3 AEs were more frequent with RT+PD-1 (15.2% vs 7.0%, P = .020). CONCLUSIONS: In unresectable HCC, adding PD-1 blockade to SBRT enhances anti-tumor activity and improves long-term survival outcomes.