Efficacy and safety of multiple treatments for small hepatocellular carcinoma: an updated systematic review and component network meta analysis

Background This is an updated component network meta-analysis to evaluate efficacy and safety of various therapeutic approaches and their combinations for small hepatocellular carcinoma (SHCC) following PRISMA 2020 guideline. Methods We screened two previously published meta-analyses on this topic, and searched PubMed, Embase, and the Cochrane Library from 1 January 2021 to 12 March 2026 for randomized controlled trials (RCTs) focusing on treatments of SHCC. We compared the efficacy and safety of surgical resection (SR), radiofrequency ablation (RFA), microwave ablation (MWA), transcatheter arterial chemoembolization (TACE), radiotherapy (RT), and their combinations. Outcomes were overall survival (OS), recurrence-free survival (RFS), and the rate of complications. Standard network meta-analysis (NMA), component NMA were performed, adding subgroup analysis, network meta-regression, and meta-regression between outcomes for sensitive analysis. This study is registered in PROSPERO (CRD420251132447). Findings We included 41 RCTs involving 5804 patients. RFA + 125 I [OS: Hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31–0.81; RFS: HR 0.51, 95% CI 0.32–0.81], TACE + RFA (OS: HR 0.66, 95% CI 0.52–0.85; RFS: HR 0.70, 95% CI 0.57–0.86), TACE + SR (OS: HR 0.30, 95% CI 0.16–0.58; RFS: HR 0.37, 95% CI 0.23–0.59) and SR (OS: HR 0.83, 95% CI 0.71–0.98; RFS: HR 0.82, 95% CI 0.71–0.94) had better OS and RFS than RFA; MWA had better RFS (HR 0.75, 95% CI 0.60–0.93), while TACE + RT might worsen RFS (HR 3.53, 95% CI 1.29–9.62). SR yielded more complications (RR 1.52, 95% CI 1.14–2.03). Better liver function (Child-Pugh A) was negatively correlated with HR of RFS (−0.16, 95% CI −0.28 to −0.04). Interpretation SR remains the foundational treatment for SHCC, and TACE + SR exhibits superior efficacy in SHCC patients. RFA + 125 I serves as a potential alternative in patients with unresectable tumors, and most locoregional treatments show effects comparable to SR for SHCC. Liver function may negatively affect relative efficacy of treatments. Funding This study is funded by 1.3.5 project for disciplines of excellence-Clinical Research Incubation Project, West China Hospital, SCU; 1.3.5 project for Artificial Intelligence West China Hospital, SCU; National Natural Science Foundation of China for Young Scientists Fund; Sichuan Science and Technology Program; (Qilu) Clinical Research of Sichuan Anticancer Association.