Comparative analysis of treatment modalities for solitary, small (≤3 cm) hepatocellular carcinoma: A systematic review and network meta-analysis of oncologic outcomes

Solitary hepatocellular carcinoma measuring ≤3 cm represents approximately 30% of hepatocellular carcinoma cases, yet treatment guidelines lack robust evidence. This study compares oncologic outcomes after ablation, liver resection, and liver transplantation for solitary, small hepatocellular carcinoma. We systematically searched databases up to 7 February 2022, for studies including adults with solitary hepatocellular carcinoma ≤3 cm treated by any ablation, liver resection, or liver transplantation. We excluded non-hepatocellular carcinoma cancers, recurrent/metastatic diseases, and alternative therapies. A frequentist network meta-analysis assessed 5-year overall survival and recurrence-free survival using only adjusted effect estimates while accounting for bias risk. We identified 80 studies (4 randomized controlled trials, 72 retrospectives, and 4 prospective cohorts) with 28,211 patients. In the network meta-analysis for 5-year overall survival (26 studies), liver transplantation was associated with the lowest mortality hazard (hazard ratio, 0.47; 95% confidence interval, 0.31-0.73, referenced to liver resection), followed by liver resection (reference), whereas ablation had the greatest mortality hazard (hazard ratio, 1.32; 95% confidence interval, 1.16-1.49, referenced to liver resection). For 5-year recurrence-free survival (19 studies), liver transplantation had the best outcome (hazard ratio, 0.36; 95% confidence interval, 0.20-0.63, referenced to liver transplantation), followed by liver resection (reference), with ablation showing the least favorable outcome (hazard ratio, 1.67; 95% confidence interval, 1.45-1.93, referenced to liver resection). This network meta-analysis provides the evidence for comparing treatment modality outcomes for solitary, small (≤3 cm) hepatocellular carcinoma. LT emerges as the superior choice for achieving a better 5-year OS, followed by liver resection, then ablation. When feasible to preserve liver function, liver resection can be prioritized. Ablation with close surveillance should be reserved for individuals unfit for surgery.