Surgery is the standard treatment option for hepatocellular carcinoma (HCC) meeting the Milan criteria, defined as single HCC ≤ 5 cm in maximum diameter or up to 3 nodules ≤3 cm. However, favorable survival outcomes have also been reported for these HCCs following radiofrequency ablation (RFA). We performed a systematic review to compare the results of hepatic resection and percutaneous RFA as a primary treatment option of HCC meeting the Milan criteria. Studies were identified by searching MEDLINE on PubMed, the Cochrane Library database and CANCERLIT using appropriate key words.

. In all the six identified observational studies, there were no statistically significant differences in overall survival rates between the two treatment modalities. The results of two randomized trials are controversial, while the power of these randomized trials is too limited to reach a reliable conclusion. In practice, the choice of treatment between surgery and RFA largely depends on the relationship between the local recurrence and perioperative mortality rates of HCC patients. Following RFA, local recurrence rates are low when a minimal safety margin ≥4-5mm is achieved. A previous simulation study of overall survival for very early stage HCC, defined as an asymptomatic solitary small HCC ≤2cm, showed that primary RFA with a 9% local recurrence rate is comparable to surgical resection with a 3% operative mortality rate.

In conclusion, acquisition of a sufficient safety margin seems to be a critical factor before recommending wider application of RFA as primary treatment for HCCs that meet the Milan criteria.