A randomized controlled trial of radiofrequency ablation and surgical resection in the treatment of small hepatocellular carcinoma

Background & Aims

The aim of this study was to compare the efficacy of radiofrequency ablation (RFA) with surgical resection (RES) in the treatment of small hepatocellular carcinoma (HCC).

Methods

A total of 168 patients with small HCC with nodular diameters of less than 4 cm and up to two nodules were randomly divided into RES (n = 84) and RFA groups (n = 84). Outcomes were carefully monitored and evaluated during the 3-year follow-up period.

Results

The 1-, 2-, and 3-year survival rates for the RES and RFA groups were 96.0%, 87.6%, 74.8% and 93.1%, 83.1%, 67.2%, respectively. The corresponding recurrence-free survival rates for the two groups were 90.6%, 76.7%, 61.1% and 86.2%, 66.6%, 49.6%, respectively. There were no statistically significant differences between the two groups in overall survival rate (p = 0.342) or recurrence-free survival rate (p = 0.122). Multivariate analysis demonstrated that the independent risk factors associated with survival were multiple occurrences of tumors at different hepatic locations (relative risk of 2.696; 95% CI: 1.189–6.117; p = 0.018) and preoperative indocyanine green retention rate at 15 min (ICG-15) (relative risk of 3.853; 95% CI: 1.647–9.015; p = 0.002).

Conclusions

In patients with small hepatocellular carcinomas, percutaneous RFA may provide therapeutic effects similar to those of RES. However, percutaneous RFA is more likely to be incomplete for the treatment of small HCCs located at specific sites of the liver, and open or laparoscopic surgery may be the better choice.

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer mortality [1], [2]. It represents a major public health problem in the Asia–Pacific region, where the incidence of viral hepatitis is high. The incidence of HCC in China alone accounts for 55% of all cases worldwide [3]. Emphasizing the importance of HCC surveillance in patients with chronic liver disease in endemic Asian countries, the treatment of small HCC (mostly early HCC) has become a focus in hepatobiliary surgery. Surgical resection is widely accepted as curative treatment for most of the patients with small HCC, who are unwilling to receive liver transplantations [4], [5]. However, local ablative techniques, such as percutaneous ethanol injection (PEI), microwave coagulation therapy (MCT), and radiofrequency ablation (RFA) have become increasingly popular in the treatment of small HCC [6], [7], [8]. Among these techniques, RFA is currently the most widely used method due to its ease of use, safety, cost-effectiveness, and minimal invasiveness [7], [9], [10], [11], [12].

Whether RFA or surgical resection is the better treatment option for small HCC has been debated since RFA was recommended as treatment option in the 2005 practice guidelines issued by the American Association for the Study of Liver Diseases (AASLD) [13]. Recently, two meta-analyses have been conducted on this matter [14], [15]. However, the conclusions drawn differ significantly. The main reason for these discrepancies is the fact that the majority of data was obtained from non-randomized controlled trials (1 RCT and 9 NRCTs in one study, 1 RCT and 7 NRCTs in another), and the overall level of clinical evidence is low. Furthermore, the conclusions drawn from two recently published randomized-controlled trials are contradictory [16], [17]. Additional credible randomized-controlled trials are necessary for clinical guidance. Over the last 10 years, frequent upgrades in radiofrequency devices and needle electrode technology have allowed clinicians to destroy tumors of increasingly larger volumes with a single RFA treatment. RFA has evolved from a palliative tool to a curative treatment modality [18], [19]. Currently, a new RFA system that consists of a rotating cluster electrode resembling a 5-cm ball when open [20], can destroy liver parenchyma with diameters of over 5 cm in vivo in a single session, single application. For tumors smaller than 4 cm in size, RFA can achieve the 1-cm safety margin, which is the standard for local surgical excision [21]. Therefore, we conducted this prospective, randomized trial to compare the long term outcomes of RFA and RES for the treatment of HCC patients with tumors smaller than 4 cm in diameter.