RFA has been widely used as a curative therapy for small HCC. The overall survival of patients with small HCC undergoing RFA is similar to that of patients receiving surgical Resection [8–10, 20, 21]. In clinical practice it is rarely possible to achieve complete ablation for tumors larger than 5 cm because of the limitation of the ablation zone [22, 23]. For patients with tumors beyond the Milan criteria, surgical treatment could be another curative option. If the tumor cannot be completely removed, palliative TACE treatment is the main treatment of choice. However, the long-term outcome for patients with unresectable HCC treated with TACE is unsatisfactory due to the inability to achieve complete tumor necrosis. Repeated TACE is often needed to completely eradicate the residual tumors, but its efficiency is limited and the rate of tumor recurrence or relapse after initial remission or stable disease is very high.
Several lines of evidence have indicated the feasibility and benefit of combination therapy of TACE and RFA. Buscarini et al. treated 14 HCC patients (with lesion size ranging from 3.8-6.8 cm, median 5.2 cm) with TACE followed by RFA. Their results suggested the possibility of treating large HCC with this procedure . Lencioni et al. similarly reported a successful outcome (82%) among patients with HCC (lesion size ranging between 3.8 and 8.5 cm) who were treated with TACE prior to RFA . Consistent with previous studies, the post-treatment CR rate of 76.2% and partial response rate of 23.8% in the present series indicate an encouraging benefit for patients with unresectable HCC beyond the Milan criteria.
RFA treatment following TACE has some advantages over TACE alone. Embolization during the TACE procedure can block arterial flow, which may reduce heat-sink effects during RFA thus increasing the volume of the zone of ablation and reducing the chance of tumor recurrence. TACE can also control or eliminate micro-metastasis, which cannot always be detected by ultrasonography, CT, or MRI. Thus, the addition of TACE may decrease the chance of micro-metastasis after RFA treatment in HCC patients with unresectable tumors beyond the Milan criteria.
With respect to prognostic factors correlated with local ablation efficiency, our results suggested that lesion diameter (< 50 mm vs. ≥ 50 mm) was statistically significant for predicting complete ablation (86.4% vs. 65%, P = 0.022). The presence of multiple lesions did not significantly affect complete ablation, although this might be because the number of nodules was confined to five in our study. It is difficult to completely destroy tumors larger than 5 cm by RFA despite multiple overlapping ablations; however, first-line TACE treatment might reduce the volume of viable tumor thus making complete ablation of the lesions possible. This treatment advantage was also proposed by Vogl, who suggested that repeated TACE might reduce the size of the treated lesions .
In this study, the 1-, 2-, and 3-year survival rates were 89%, 61%, and 43%, respectively. These rates are consistent with those of other studies. Veltri reported 1- and 2-year survival rates of 89.7% and 67.1% for TACE-RFA combined therapy for unresectable non-early HCC (size 30–80 mm, mean 48.9 mm) . Similarly, Liao et al.  administrated TACE followed by RFA in the treatment of unresectable HCC (size 30–120 mm, mean 58.9 mm) with 1-, 2- and 3-year survival rates of 84%, 57%, and 38%, respectively. Our multivariate analysis showed that tumor size and serum AFP level before treatment were prognostic factors for overall survival. A high pretreatment level of AFP has previously been reported to be associated with poorer survival, reflecting not only tumor cell proliferation but also active disease with continuous necrosis and regeneration [29, 30].
We found that TACE-RFA combined therapy had a low rate of major complications. No permanent adverse sequelae or treatment-related deaths were observed. Thus, combination therapy of TACE followed by RFA appears to be relatively safe.