<b>Purpose</b><br/>Tumor location influences the effectiveness and safety of RFA. This study evaluated RFA outcomes as first-line therapy for HCC <3 cm, focusing on tumor location impact. <br/><b>Materials and Methods</b><br/>In this retrospective cohort study, 281 patients with newly diagnosed HCC <3 cm in up to three lesions treated with RFA between 2003 and 2019 were analyzed. The tumor location was categorized as superficial (outer third), mid-portion (middle third), or deep (near vena cava), using an imaginary line from the liver surface to the vena cava. Perivascular tumors were defined as those abutting portal or hepatic veins. Recurrence-free survival (RFS) among location groups was compared with risk factors analyzed via Cox regression. <br/><b>Results</b><br/>Patients (mean age, 61.1 ± 11.1 years) were predominantly male (73.3%), hepatitis B virus surface antigen–positive (66.2%), and of Child-Pugh class A (97.5%). Deep tumors had shorter RFS than superficial/mid-portion tumors (HR, 1.87; 95% CI, 1.20 to 2.93; p = 0.005), as did perivascular versus non-perivascular tumors (HR, 1.87; 95% CI, 1.16 to 3.00; p = 0.008). Group C (deep + perivascular, n = 10) had shorter RFS than group A (no risk factors: HR, 3.12; 95% CI, 1.50 to 6.45; p = 0.002) and group B (one risk factor: HR, 1.59; 95% CI, 1.05 to 2.40; p = 0.028). Multivariable analysis identified tumor depth, perivascular location, size >2 cm, creatinine, and prothrombin time as independent predictors of shorter RFS. <br/><b>Conclusion</b><br/>Tumor depth and proximity to vasculature independently predict RFS in small HCCs treated with RFA, highlighting the role of tumor location in determining patient prognosis.

Transarterial chemoembolization (TACE) has long been the standard locoregional therapy for unresectable hepatocellular carcinoma, while transarterial radioembolization (TARE) using yttrium-90 microspheres has emerged as a promising alternative driven by advances in dosimetry and improved outcomes. TARE offers high complete response rates, durable local control, and minimal post-embolization syndrome, particularly in patients with localized or large tumors and preserved hepatic function. However, its broader use is limited by radiation-related toxicity, technical challenges, and socioeconomic factors, including high cost and limited repeatability. In contrast, TACE remains widely applicable, repeatable, and cost-effective, achieving excellent tumor control through refined superselective techniques, especially in Korea. Rather than competing modalities, TARE and TACE should be integrated within a tailored treatment strategy, with the choice determined by tumor characteristics, hepatic reserve, and institutional expertise.