Transarterial chemoembolization combined with sorafenib versus monotherapy for unresectable hepatocellular carcinoma: An umbrella review of meta-analyses

Abstract Background: This umbrella review synthesizes evidence from meta-analyses and reviews comparing transarterial chemoembolization (TACE) combined with sorafenib versus monotherapy for unresectable hepatocellular carcinoma. Methods: Following PRIOR guidelines, PubMed, Google Scholar, Web of Science, and Scopus were searched from inception to December 2024. Outcomes included overall survival (OS), time to progression (TTP), disease control rate (DCR), and objective response rate (ORR). Corrected covered area (CCA) assessed overlap, and methodological quality was evaluated using AMSTAR-2. Results: Of 13,821 records, 9 meta-analyses were included, with substantial overlap (CCA: 49%). Eight reviews assessed OS; five reported a significant survival benefit (hazard ratio [HR] 0.62–0.74, p < 0.001), while two found no significant effect (HR 0.75–0.97, p > 0.05). Eight evaluated TTP; six showed a significant reduction in risk (HR 0.61–0.75, p < 0.05), while two reported non-significant findings (HR 0.74–0.77, p > 0.05). Four assessed DCR; two reported a significant benefit (odds ratio [OR] 0.52–4.72, p < 0.01), one showed a non-significant trend (OR: 1.57, p = 0.06), and one found no significant effect (relative risk [RR] 1.04, p = 0.57). Six assessed ORR; three reported a significant increase in response (OR 2.19–3.59, p < 0.01), one showed a significant reduction (OR 0.85, p < 0.001), one found no significant effect (RR 1.20, p = 0.26), and one reported a significant protective effect (OR 0.39, p = 0.008). Conclusions: TACE plus sorafenib improves TTP, ORR, and OS in unresectable HCC and highlights the need for personalized treatment and further research.