Hepatic Resection for Hepatocellular Carcinoma in the Era of Molecular-targeted Agents and Immune Checkpoint Inhibitors in Japan

Abstract

Hepatic resection or liver transplantation for hepatocellular carcinoma (HCC) represents the only chance for achieving a cure. For the past several decades in Japan, aggressive hepatic resection has been performed for advanced HCC, with consequent good outcomes. According to the 21st Nationwide Follow-Up Survey of Primary Liver Cancer in Japan, 38.3% of patients were treated with hepatic resection or liver transplantation as the initial treatment. The median overall survival of patients who underwent surgery was 57.0 months, and the 5- and 10-year survival rates were 48.4% and 25.2%, respectively. Since 1964, a total of 10,038 liver transplants (595 deceased-donor and 9,443 living-donor transplants) have been performed in Japan. Neoplastic disease, including HCC, was reported to be the third-most common cause of liver transplantation, and the cumulative 1-, 3-, 5-, and 10-year survival rates of living-donor liver transplants for HCC were 85.0%, 76.2%, 70.9%, and 63.1%, respectively. However, molecular-targeted agents, including sorafenib and lenvatinib, have recently been developed. Furthermore, a significantly longer survival with atezolizumab, which is an immune checkpoint inhibitor, plus bevacizumab was observed compared with sorafenib for unresectable HCC patients. Herein, we review the current status of hepatic resection and liver transplantation for HCC in Japan and discuss the role of hepatic resection in the era of molecular-targeted agents and immune checkpoint inhibitors, as well as the need for a definition of borderline resectable-HCC.