Efficacy and safety of various primary treatment strategies for very early and early hepatocellular carcinoma: a network meta-analysis

Abstract

Background: Several treatments are available for treatment of early and very early-stage Hepatocellular Carcinoma, also known as small Hepatocellular Carcinoma (SHCC). However, there is no consensus with regards to the efficacies of these methods. We aimed at identifying the most effective initial treatment strategy for SHCC through Bayesian network meta-analyses. Methods: Studies published between January, 2010, and February, 2021 were searched in EMBASE, Cochrane Library, PubMed and Web of science databases, and conference proceedings for trials. The included studies reported the survival outcomes of very early and early Hepatocellular Carcinoma patients subjected to radiofrequency ablation (RFA), microwave ablation (MWA), surgical resection (SR), transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), minimally invasive liver surgery (MIS), stereotactic body radiotherapy (SBRT) and cryoablation (CA). Then, data were extracted from studies that met the inclusion criteria. Patient survival data were retrieved from the published Kaplan–Meier curves and pooled. A Bayesian random-effects model was used to combine direct and indirect evidence. Results: A total of 2058 articles were retrieved and screened, from which 45 studies assessing the efficacies of 8 different treatments in 11,364 patients were selected. The included studies had high methodological quality. Recurrence free survival* (progression/recurrence/relapse/disease/tumor-free survival were combined and redefined as RFS*) and overall survival (OS) outcomes were highest in MIS-treated patients (HR 0·57, 95% confidence intervals [CI] 0·38–0·85; HR 0.48,95% CI 0.36–0.64, respectively), followed by SR-treated patients (HR 0.60, 95% CI 0.50–0.74; HR 0.62, 95% CI 0.55–0.72, respectively). TACE was highly efficacious (58.9%) at decreasing the rates of major complications. Similar findings were obtained through sensitivity analysis, and in most of the prognostic subgroups. Conclusions: MIS and SR exhibited the highest clinical efficacies, however, they were associated with higher rates of complications. Ablation is effective in small tumors, whereas SBRT is a relatively promising treatment option for SHCC. More well-designed, large-scale randomized controlled trials should be performed to validate our findings.