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Background/Aims: Local ablation therapy (LAT) is primarily recommended for solitary inoperable hepatocellular carcinomas (HCCs) of ≤3 cm in diameter. However, only two-thirds of uninodular small HCCs are suitable for LAT, and the second-best treatment option for managing these nodules is unclear. We aimed to compare the therapeutic outcomes of chemoembolization and radiotherapy in small HCCs unsuitable for LAT. Methods: The study included 651 patients from a tertiary referral center who underwent planning sonography for LAT. These patients had 801 solitary HCCs of ≤3 cm in diameter and were treated with LAT, chemoembolization, or radiotherapy. Local tumor progression (LTP)-free survival and overall survival (OS) were measured according to the type of treatment of the index nodule. Results: LAT, chemoembolization, and radiotherapy were used to treat 561, 185, and 55 nodules in 467, 148, and 36 patients, respectively. LTP-free survival was significantly shorter in patients treated with chemoembolization than for those treated with LAT (multivariate hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.61 to 3.47) but not for those treated with radiotherapy (HR, 0.83; 95% CI, 0.38 to 1.83). However, OS was not affected by treatment modality. Matching and weighting analyses confirmed that radiotherapy gave comparable results to chemoembolization in terms of OS despite better LTP-free survival (HR, 2.91; 95% CI, 1.13 to 7.47 and HR, 3.07; 95% CI, 1.11 to 8.48, respectively). Conclusions: Our data suggest that chemoembolization and radiotherapy are equally effective options for single small HCCs found to be unsuitable for LAT after sonographic planning. Better-fit indications for each procedure should be established by specifically designed studies.
