Letter to the Editor: Hepatic Resection Compared to Chemoembolization in Intermediate- to Advanced-Stage Hepatocellular Carcinoma: A Comment For Moving Forward.

Abstract

Supported by the Graduate Course Construction Project of Guangxi Medical University (YJSA2017014). Potential conflict of interest: Nothing to report. To the Editor: Treatment of hepatocellular carcinoma (HCC) depends on disease staging, which is usually performed according to the Barcelona Clinic Liver Cancer (BCLC) system. Although the BCLC system is recommended in the guidelines from the European Association for the Study of the Liver,1 the American Association for the Study of Liver Diseases,2 and the European Society for Medical Oncology,3 its treatment recommendations for intermediate and advanced HCC are inconsistent with the literature. The BCLC system recommends only transarterial chemoembolization (TACE) and sorafenib for intermediate and advanced HCC, yet several studies have suggested that expanding the selection criteria for hepatectomy can increase overall survival of these patients. Now, an elegant meta‐analysis by Hyun and coworkers4 suggests that, indeed, based on the evidence in 18 high‐quality studies, hepatectomy can increase overall survival in patients with intermediate and advanced HCC. We applaud Hyun and colleagues for providing the largest study so far that evaluates the idea of expanding indications for hepatectomy in HCC. At the same time, their conclusions should be interpreted with caution in light of some concerns. The first is that the authors of the meta‐analysis did not clearly define intermediate HCC. Among the studies they included, 39%‐86% of patients had a single large tumor (> 5 cm) in the intermediate subgroup (table 1 of the meta‐analysis). Although earlier versions of the BCLC system defined single HCC of 5 cm as the cutoff between early and intermediate stages, more recent studies of the BCLC group and official guidelines indicate that single HCC of any size should be classified as early disease in the absence of portal hypertension, satellites, and macrovascular invasion.1 Recent guidelines, in fact, classify only multinodular HCC as intermediate disease.1 Therefore, the use of “intermediate stage” in the title of the meta‐analysis may not be appropriate. The second concern is the fact that references 17 and 30 in the meta‐analysis involved overlapping patient populations. In addition, only 9 of the 18 studies compared hepatectomy and TACE in parallel. We again congratulate Hyun and coworkers on their interesting study to expand the indications for hepatectomy to patients with large/multinodular HCC and advanced disease. High‐level evidence such as their meta‐analysis will hopefully encourage the updating of the BCLC system.