The goal of RFA is to induce thermal injury to the tissue through electromagnetic energy deposition. In the more popular monopolar mode, the patient is part of a closed-loop circuit, that includes a RF generator, an electrode needle, and a large dispersive electrode (ground pads). An alternating electric field is created within the tissue of the patient. Because of the relatively high electrical resistance of tissue in comparison with the metal electrodes, there is marked agitation of the ions present in the target tissue that surrounds the electrode, since the tissue ions attempt to follow the changes in direction of alternating electric current. The agitation results in frictional heat around the electrode. The discrepancy between the small surface area of the needle electrode and the large area of the ground pads causes the generated heat to be focused and concentrated around the needle electrode. Several electrode types are available for clinical RFA, including internally cooled electrodes and multi-tined expandable electrodes with or without perfusion [13]. An important factor that affects the success of RFA is the ability to ablate all viable tumor tissue and possibly an adequate tumor-free margin. Ideally, a 360 °, 0.5–1 cm-thick ablative margin should be produced around the tumor. This cuff would ensure that the peripheral portion of the tumor as well as any microscopic invasions located in its close proximity have been eradicated [13] (Fig. 1).

RFA has been the most widely assessed alternative to PEI for local ablation of HCC. Five randomized controlled trials (RCTs) have compared RFA versus PEI for the treatment of early-stage HCC. These investigations consistently showed that RFA has higher anticancer effect than PEI, leading to a better local control of the disease [14–18] (Table 2). The assessment of the impact of RFA on survival has been more controversial. While a survival benefit was identified in the three RCTs performed in Asia, the two European RCTs failed to show statistically significant differences in overall survival between patients who received RFA and those treated with PEI, despite the trend favoring RFA (Table 2). In patients with early-stage HCC treated with percutaneous ablation, long-term survival is influenced by multiple different interventions, given that about than 80 % of the patients will develop recurrent intrahepatic HCC nodules within 5 years of the initial treatment and will received additional therapies [19]. Nevertheless, three independent meta-analyses including all RCTs, have confirmed that treatment with RFA offers a survival benefit as compared with PEI, particularly for tumors larger than 2 cm, thus establishing RFA as the standard percutaneous technique [20–22]. For studies that reported major complications; however, the incidence in RFA-treated patients was 4.1 % (95 % CI, 1.8–6.4 %), compared to 2.7 % (95 % CI, 0.4–5.1 %) observed in PEI-treated patients [23]. This difference was not statistically significant; nevertheless, this safety profile should be taken into consideration as part of the overall risk/benefit profile in each individual case.

Recent reports on long-term outcomes of RFA-treated patients have shown that in patients with Child-Pugh class A and early-stage HCC, 5 year survival rates are as high as 51–64 %, and may reach 76 % in patients who meet the BCLC criteria for surgical resection [19, 24–26] (Table 3). Caution, however, is needed when interpreting and generalizing these results, in particular in the light of studies that suggest a nonnegligible rate of incomplete histopathological response after RFA. In fact, the ability of RFA to achieve a complete tumour eradication appears to be dependent on tumor size and location. In particular, histological studies performed in liver specimens of patients who underwent RFA as bridge treatment to transplantation showed that the presence of large (3 mm or more) abutting vessels result in a drop of the rate of complete tumor necrosis to less than 50 %, because of the heat loss due to perfusion-mediated tissue cooling within the area to be ablated [27] (Fig. 2). Other clinical experiences have suggested that treatment of HCC tumors in subcapsular location or adjacent to the gallbladder is associated with an increased risk of incomplete ablation and local tumor progression [28, 29]. Treatment of tumors in such unfavorable locations has also been shown to result in a significant increase of major complications [30, 31].

To increase the efficacy of RFA, especially in tumors of intermediate size (3–7 cm), several authors have suggested the combined use of transcatheter arterial chemoembolization (TACE) and RFA. A combination including TACE followed by RFA has been used to minimize heat loss due to perfusion-mediated tissue cooling and increase the local therapeutic effect of RFA [32–35]. On the other hand, TACE with drug-eluting beads has been performed after an RFA procedure to increase tumor necrosis by exposing to high drug concentration the peripheral part of the tumor, where only sublethal temperatures may be achieved in a standard RFA treatment [36]. Other investigators have suggested the combined use of percutaneous approaches, such ethanol injection and RFA [37]. Unfortunately, despite several investigations reporting promising results have been reported, no definitive proof of clinical efficacy was reached, as no robust RCT comparing the survival outcomes achieved with such combinations of interventional techniques over those obtained with either therapy alone has been completed so far.