Transarterial Radioembolization with Yttrium-90 and SIRT Versus Conventional Transarterial Chemoembolization for Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

Abstract

Background: Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are primary locoregional therapies for unresectable hepatocellular carcinoma (HCC). However, their comparative efficacy remains debated. We aimed to systematically review and meta-analyze the evidence comparing TARE (Yttrium-90 or SIRT) versus TACE (conventional or drug-eluting bead) for intermediate or advanced HCC.

Methods: Following PRISMA guidelines, we searched PubMed, Embase, Web of Science, Cochrane Library, and Scopus (until April 2025) for randomized controlled trials (RCTs) and comparative observational studies comparing TARE vs. TACE in adults with BCLC stage B/C HCC. Primary outcomes were Overall Survival (OS) and time to progression (TTP)/progression-free survival (PFS). Secondary outcomes included objective response rate (ORR) and adverse events. Risk of bias was assessed using RoB 2 (RCTs) and ROBINS-I (non-randomized studies). Meta-analyses were performed using a random-effects model with the generic inverse variance method.

Results: From 859 records (854 database; five other sources), 778 remained after removal of 81 duplicates or ineligible items and underwent title/abstract screening. 18 full texts were assessed, of which six studies (two RCTs and four cohort/propensity-matched comparisons; total N ≈ 443) met inclusion criteria. In the meta-analysis of overall survival (OS), TARE/SIRT significantly reduced the hazard of death compared to TACE (HR 0.68, 95% CI 0.55-0.86; Z=3.32, p=0.0009), with low heterogeneity (I²=3%). PFS or TTP also favored radioembolization, yielding a pooled HR of 0.54 (95% CI 0.44-0.67; Z=5.63, p<0.00001) and moderate heterogeneity (I²=41%). ORR did not differ significantly between modalities (OR 0.87, 95% CI 0.41-1.82; Z=0.37, p=0.71; I²=10%). Grade ≥ 3 treatment-related adverse events trended lower with TARE/SIRT but without statistical significance (OR 0.60, 95% CI 0.29-1.25; Z=1.36, p=0.18; I²=0%). Overall, radioembolization demonstrated superior survival and disease control compared to chemoembolization, without a clear increase in severe toxicity.

Conclusion: In conclusion, this meta-analysis demonstrates that (TARE/SIRT) offers a significant survival advantage and superior locoregional disease control compared to conventional and drug-eluting bead chemoembolization (TACE), without a concomitant increase in severe toxicity. These findings support the consideration of TARE/SIRT as a preferred locoregional therapy for unresectable hepatocellular carcinoma, while underscoring the need for further randomized trials to refine patient selection, optimize treatment sequencing, and validate long-term safety and efficacy.