Radiotherapy versus local ablation therapy for the treatment of hepatocellular carcinoma: A systematic review and meta-analysis.

Abstract

547 Background: Local ablation therapies, including radiofrequency ablation (RFA) and microwave ablation (MWA), are common curative options for small hepatocellular carcinoma (HCC). External beam radiotherapy (EBRT), such as stereotactic body radiotherapy (SBRT) and proton beam therapy (PBT), has recently emerged as a non-invasive alternative. Both approaches are increasingly adopted in clinical practice, each with strengths and limitations by clinical factors. However, direct comparative evidence between EBRT and local ablation therapy remains limited. This study aimed to evaluate whether EBRT differs from local ablation therapy in terms of local progression-free survival (LPFS), overall survival (OS), progression-free survival (PFS), and treatment-related toxicities. Methods: We systematically searched PubMed/MEDLINE, Embase, Cochrane Library, and KoreaMed for studies published up to June 2025, following PRISMA guidelines. Eligible studies were retrospective or prospective comparisons of EBRT (SBRT or PBT) vs ablation (RFA/MWA) reporting local recurrence or survival outcomes. Exclusion criteria were studies in which treatments were given with neoadjuvant/adjuvant intent, designed as bridging for liver transplantation, included patients with extrahepatic metastases, or conducted with palliative intent. Hazard ratios (HRs) for time-to-event outcomes and odds ratios (ORs) for binary outcomes were pooled using a random-effects model (DerSimonian–Laird method). Publication bias was evaluated using funnel plots and Egger’s test. Results: Of 1,311 records screened, 12 studies comprising 2,768 patients met inclusion criteria. The pooled overall local recurrence rate was significantly lower with EBRT compared with ablation (OR 0.36, 95% CI 0.25–0.50; P <0.0001; I² = 0%). EBRT also significantly improved LPFS (HR 0.41, 95% CI 0.34–0.50; P <0.0001), and this benefit was consistent across tumor sizes, both ≤2 cm (HR 0.32, 95% CI 0.19–0.55) and >2 cm (HR 0.34, 95% CI 0.20–0.59). PFS showed a borderline difference (HR 0.80, 95% CI 0.64–1.00; P = 0.049). OS was also comparable (HR 1.24, 95% CI 0.83–1.84; P = 0.291), although heterogeneity was substantial (I² >50%), reflecting differences in study design and patient populations. Severe toxicities, defined as grade ≥3, were comparable between groups for both acute events (OR 0.78, 95% CI 0.27–2.24; P = 0.649) and late events (OR 1.29, 95% CI 0.85–1.95; P = 0.233), with EBRT tending toward fewer acute events. No significant publication bias was detected for survival or toxicity outcomes on funnel plots or Egger’s test (all P >0.05). Conclusions: EBRT achieved better local tumor control compared with ablation, while survival and toxicity outcomes were comparable. Both approaches remain established local treatments, and EBRT should be recognized as an effective local therapy in appropriately selected HCC patients.