Radiofrequency ablation of small hepatocellular carcinoma in cirrhotic patients awaiting liver transplantation: a prospective study

Abstract

Objective: Determine the histologic response-rate (complete versus partial tumor extinction) after single radiofrequency ablation (RFA) of small hepatocellular carcinoma (HCC) arising in cirrhosis. Investigate possible predictors of response and assess efficacy and safety of RFA as a bridge to liver transplantation (OLT).

Background: RFA has become the elective treatment of local control of HCC, although histologic data supporting radiologic assessment of response are rare and prospective studies are lacking. Prognostic impact of repeated RFA for HCC persistence is also undetermined.

Methods: Percentage of RFA-induced necrosis and tumor persistence-rate at various intervals from treatment was studied in 60 HCC (median: 3 cm; Milan-Criteria IN: 80%) isolated in 50 consecutive cirrhotic patients undergoing OLT. Single-session RFA was the only treatment planned before OLT. Histologic response determined on explanted livers was related to 28 variables and to pre-OLT CT scan.

Results: Mean interval RFA-->OLT was 9.5 months. Post-RFA complete response rate was 55%, rising to 63% for HCC </=3 cm. Tumor size was the only prognostic factor significantly related to response (P = 0.007). Tumor satellites and/or new HCC foci (56 nodules) were unaffected by RFA and significantly correlated with HCC >3 cm (P = 0.05). Post-RFA tumor persistence probability increased with time (12 months: 59%; 18 months: 70%). Radiologic response rate was 70%, not significantly different from histology. Major post-RFA morbidity was 8%. No mortality, Child deterioration, patient withdrawal because of tumor progression was observed. Post-OLT 3-year patient/graft survival was 83%.

Conclusions: RFA is a safe and effective treatment of small HCC in cirrhotics awaiting OLT, although tumor size (>3 cm) and time from treatment (>1 year) predict a high risk of tumor persistence in the targeted nodule. RFA should not be considered an independent therapy for HCC.

FIGURE 1. Patterns of response after radiofrequency ablation of hepatocellular carcinoma (histologic determination on explanted livers). Complete response (A, B). A, Intense eosinophilic staining of coagulative necrosis with no residual tumor cells in an HCC nodule 4 months after RFA (H&E, × 20). B, Coagulative necrosis surrounded by fibrous pseudocapsula 1 year after RFA (H&E, × 40); at higher magnification (inset, × 100) preservation of the tissue architecture with islands of fading “ghost” hepatocytes are observed. Partial response (C, D). C, Residual vital tumor (T) is detected inside coagulative necrosis (cn) induced by radiofrequency ablation performed 13 months previously, with a fibrous band dividing the 2 areas (H&E, × 40). D, Coagulative necrosis surrounded by tumor capsule, with a small HCC satellite (Ts), just outside the rim of the RFA-extinguished tumor (H&E, × 100).

FIGURE 2. Cumulative probability of hepatocellular carcinoma persistence after radiofrequency ablation. The unforeseeable time period from RFA to tumor removal (at the time of liver transplantation) offered the opportunity for estimating the probability of residual HCC in the targeted nodule. The cumulative probability curve shows an increased risk of post-RFA incomplete necrosis and HCC persistence that increases with time (see text).