Abstract
BACKGROUND: Transarterial radioembolization (TARE) using Yttrium-90 microspheres has emerged as a promising locoregional therapy for patients with advanced hepatocellular carcinoma (HCC). However, the efficacy and safety of TARE compared to conventional treatments remain uncertain. This meta-analysis aimed to comprehensively evaluate the survival outcomes and safety profile of TARE in advanced HCC. METHODS: A systematic literature search was conducted in PubMed, Embase, Cochrane Library, and Web of Science up to May 2025, following the PRISMA guidelines. Studies comparing TARE with conventional or systemic therapies in advanced HCC were included. Pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for adverse events (AEs) were calculated using random-effects models. Subgroup and meta-regression analyses explored the influence of study design, liver function (Child-Pugh, ALBI grade), and combined therapies. RESULTS: Forty studies encompassing over 10,000 patients were included. TARE significantly improved OS (pooled HR = 0.72, 95% CI 0.63-0.83) and PFS (pooled HR = 0.78, 95% CI 0.69-0.89) compared with controls. Rates of grade ≥3 adverse events were lower in the TARE group (pooled OR = 0.74, 95% CI 0.59-0.93). Subgroup analyses indicated consistent benefits across retrospective and prospective studies, and in patients with Child-Pugh A-B liver function. Meta-regression revealed that younger age and higher objective response rate were associated with improved outcomes. CONCLUSION: TARE with Yttrium-90 microspheres confers significant survival benefits and acceptable safety in advanced HCC. These findings support the integration of TARE into multidisciplinary management strategies for advanced HCC, particularly in patients unsuitable for surgical or systemic therapies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD420251163947).