In this meta-analysis, meta-analysis showed that ES-HCC patients undergoing LR had better OS and DFS than those undergoing RFA. However, ES-HCC is a complex conceptual set of HCC with different diameters (0-5cm) and different numbers (1–3 tumors). Additionally, details related to hepatectomy (including anatomic hepatectomy, laparoscopic hepatectomy, tumor resection margin) and radiofrequency ablation (including radiofrequency ablation guidance, ablation margin and ablation equipment) will affect the survival of patients with HCC. Subgroup analysis showed that RFA and LR can provide similar OS and RFS for very early stage HCC (single tumor and the diameter less or equal to 2cm). Additionally, when the tumor was single and less or equal to 3cm, or the ablation margin wa larger than 1cm, the OS provided by RFA and LR was similar, although the RFS was still better in LR. The incidence of postoperative complications was significantly lower, and hospitalization was significantly shorter among ES-HCC patients undergoing RFA.
The primary advantage of RFA over LR is less invasiveness. RFA causes minor damage to the surrounding healthy liver parenchyma, thus maximally preserving the liver remnant (63). As a result, the complication rates were much lower, and the length of hospital stay was much shorter.
The main reason for the inferiority of RFA to LR in long-term survival is the higher local recurrence rate related to incomplete ablation (64). The efficacy of RFA could be affected by several factors, including surgeons’ experience, tumor number, tumor size, and tumor location (6, 65, 66). The insufficient ablation led to a high local recurrence rate (65). On the other hand, LR could remove both the tumor and its micro neoplastic embolus by radically resecting primary cancer and adjacent liver parenchymal to guarantee a negative margin (67, 68). In the subgroup analysis, we found that RFA can achieve similar OS to LR when the ablation margin was lager than 1cm. Hence, the complete removal of the primary tumor and potential micrometastasis by LR might explain cothe superior long-term prognosis of early-stage HCC patients in the LR group.
Several meta-analyses have been available to compare the effects of RFA versus LR for HCC. Xu et al. performed a meta-analysis of five RCTs comparing survival outcomes of patients with small HCC who underwent LR or RFA (31). RFA led to decreased overall survival compared with LR at 5 years, but the trial sequential analysis indicated that additional trials were necessary to confirm this conclusion. Additionally, time-to-event outcomes are most appropriately analyzed using HR (34). Another recently published network meta-analysis by Zhang et al., which included RCTs and PSM studies, showed that LR is superior to RFA in OS and DFS (69). The results are consistent with ours. However, their meta-analysis did not include one RCT and several PSM studies newly published in 2022. As far as we know, our meta-analysis is the most updated, with a maximum number of high-quality studies being included. More than 11,000 ES-HCC patients from 5 countries in the east and west were included to make the results more reliable and clinically meaningful. Moreover, sensitivity, subgroup, and meta-regression analyses provided ample evidence supporting our conclusion. The most important is that we focused on special subgroups which previous meta-analysis not did, including tumor number, tumor size, surgical margin, ablation margin, and even different guidance for RFA.
It should be noted that there are limitations for this study. First, we included both RCTs and PSM studies. Although the propensity score matching method could reduce baseline differences between groups, the deviations could not be eliminated compared with RCTs. Second, tumor heterogeneity could not be avoided. Although all the cases were ES-HCC, tumor number and size varied among patients in the included studies. Hence, we conducted a subgroup analysis; however, we found no significant difference between the two groups in OS among patients with a single tumor size of < 3 cm. However, extended subgroup analysis based on tumor number and tumor size is limited due to limited data. Third, the proportion of open LR or LH, anatomic or non-anatomic LR are also inconsistent among included articles. Furthermore, with the development of RFA technology, various RFA techniques were used in different studies at different times. The influence of such heterogeneity has not been determined.