External beam radiotherapy versus local ablation therapy for the treatment of hepatocellular carcinoma: a systematic review and meta-analysis.

Abstract

Local ablation therapies (LATs), including radiofrequency (RFA) and microwave ablation (MWA), are established for small hepatocellular carcinoma (HCC) as standard treatment. External beam radiotherapy (EBRT), including stereotactic body radiotherapy (SBRT) and proton beam therapy (PBT), has emerged as a non-invasive alternative; however, direct comparative evidence remains limited. We conducted a systematic review and meta-analysis comparing the efficacy and safety of EBRT versus LAT in patients with HCC. PubMed/MEDLINE, Embase, Cochrane Library, and KoreaMed were searched through June 2025 per PRISMA guidelines. Eligible studies included retrospective or prospective comparisons of EBRT (SBRT/PBT) with LAT (RFA/MWA) reporting recurrence or survival. Hazard ratios (HRs) and odds ratios (ORs) were pooled using random-effects models. Twelve studies (2,768) patients were included. Compared with LAT, EBRT was associated with significantly lower local recurrence (OR 0.36, 95% confidence interval [CI] 0.25-0.50; P<0.001; I² = 0%) and improved local progression-free survival (HR 0.41, 95% CI 0.34-0.50; P <0.001), regardless of tumor size. Progression-free survival favored EBRT (HR 0.80, 95% CI 0.64-1.00; P = 0.049), whereas overall survival did not differ significantly between modalities (HR 1.24, 95% CI 0.83-1.84; P = 0.291). Severe toxicities (grade ≥3) were comparable between groups for acute (OR 0.78, 95% CI 0.27-2.24) and late events (OR 1.29, 95% CI 0.85-1.95). EBRT was associated with better local control without significant differences in survival or toxicity compared with LAT. These findings support the safety and efficacy of EBRT for local treatment of patients with liver-confined HCC.