Combining radiofrequency ablation and ethanol injection may achieve comparable long-term outcomes in larger hepatocellular carcinoma (3.1-4 cm) and in high-risk locations.

Radiofrequency ablation (RFA) is more effective for hepatocellular carcinoma (HCC) < 3 cm. Combining percutaneous ethanol injection and RFA for HCC can increase ablation; however, the long-term outcome remains unknown. The aim of this study was to compare long-term outcomes between patients with HCC of 2-3 cm versus 3.1-4 cm and in high-risk versus non-high-risk locations after combination therapy. The primary endpoint was overall survival and the secondary endpoint was local tumor progression (LTP). Fifty-four consecutive patients with 72 tumors were enrolled. Twenty-two (30.6%) tumors and 60 (83.3%) tumors were of 3.1-4 cm and in high-risk locations, respectively. Primary technique effectiveness was comparable between HCC of 2-3 cm versus 3.1-4 cm (98% vs. 95.5%, p = 0.521), and HCC in non-high risk and high-risk locations (100% vs. 96.7%, p = 1.000). The cumulative survival rates at 1 year, 3 years, and 5 years were 90.3%, 78.9%, and 60.3%, respectively, in patients with HCC of 2-3 cm; 95.0%, 84.4%, and 69.3% in HCC of 3.1-4.0 cm (p = 0.397); 90.0%, 71.1%, and 71.1% in patients with HCC in non-high-risk locations; and 92.7%, 81.6%, and 65.4% in high-risk locations (p = 0.979). The cumulative LTP rates at 1 year, 3 years, and 5 years were 10.2%, 32.6%, and 32.6%, respectively, in all HCCs; 12.6%, 33.9%, and 33.9% in HCC of 2-3 cm; 4.8%, 29.5%, and 29.5% in HCC of 3.1-4 cm (p = 0.616); 16.7%, 50.0%, and 50.0% in patients with HCC in non-high-risk locations; and 8.8%, 29.9%, and 29.9% in patients with HCC in high-risk locations (p = 0.283). The cumulative survival and LTP rates were not significantly different among the various subgroups. Combining RFA and percutaneous ethanol injection achieved comparable long-term outcomes in HCCs of 2-3 cm versus 3.1-4.0 cm and in high-risk versus non-high-risk locations. A randomized controlled or cohort studies with larger sample size are warranted.