Trends in treatment for hepatocellular carcinoma in Japan

Main Article Content

Yoshihiro Sakamoto Ryota Matsuki Takaaki Arai Masaharu Kogure Yutaka Suzuki

Abstract

Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer deaths in Japan, and it has gradually decreased in the last quarter century. The reason for the decrease in HCC patients is the decrease of patients with hepatitis C virus due to avoiding unnecessary blood transfusions and development of direct-acting antiviral agents (DAAs), which have been available since 2014, along with interferon and oral antiviral agents in Japan. On the other hand, the numbers of HCC patients with non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD) are increasing. In the treatment strategy for HCC in the Japanese guideline, the algorithm involves five clinicopathological factors: liver function (assessed using the Child-Pugh classification, liver damage score, and the ICG-R15 value), presence of extrahepatic metastases, presence of vascular invasion, number of tumors (within 3 or more than 4), and tumor size (within 3 cm or over 3 cm). Surgical resection is sometimes indicated for extrahepatic metastases in patients with well-controlled intrahepatic HCC, and for advanced HCC with vascular invasion, hepatectomy is also recommended as one of the treatment options according to the results of a nationwide survey in Japan. In the latest Japanese guideline, the recommended chemotherapy for advanced HCC is lenvatinib or sorafenib as first-line and regorafenib as second-line therapy. Currently, based on the results of various clinical trials for advanced HCC, the therapeutic options for advanced HCC have increased, such as combination therapy of atezolizumab and bevacizumab, ramucirumab, and cabozantinib. Reports of conversion surgery after chemotherapy have also increased, and the development of multidisciplinary treatment for advanced HCC will be of further interest in the future.

Keywords: Hepatocellular carcinoma, Japanese guideline, multidisciplinary treatment

Article Details

How to Cite
SAKAMOTO, Yoshihiro et al. Trends in treatment for hepatocellular carcinoma in Japan. Medical Research Archives, [S.l.], v. 9, n. 7, july 2021. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/2485>. Date accessed: 18 apr. 2024. doi: https://doi.org/10.18103/mra.v9i7.2485.
Section
Review Articles

References

1. National Cancer Center Cancer Information Service. Latest Cancer Statistics
(https://ganjoho.jp/reg_stat/statistics/stat/ summary.html)
2. The Japan society of hepatology (2017), Clinical Practice Guidelines for Hepatocellular Carcinoma 2017, Japan, Kenehara
3. Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391(10127):1301-1314.
4. Izumi N, Hasegawa K, Nishioka Y, et al. A multicenter randomized controlled trial to evaluate the efficacy of surgery vs. radiofrequency ablation for small hepatocellular carcinoma(SURF trial). J Clin Oncol 2019; 37: suppl
5. Kubo S, Nishiguchi S, Hirohashi K, et al. Clinicopathological criteria for multicentricity of hepatocellular carcinoma and risk factors for such carcinogenesis. Jpn J Cancer Res. 1998;89(4):419-426.
6. Ishizawa T, Hasegawa K, Aoki T, et al. Neither multiple tumors nor portal hypertension are surgical contraindications for hepatocellular carcinoma. Gastroenterology. 2008;134(7):1908-1916.
7. Ho MC, Huang GT, Tsang YM, et al. Liver resection improves the survival of patients with multiple hepatocellular carcinomas. Ann Surg Oncol. 2009;16(4):848-855.
8. Poon RT, Fan ST, Wong J. Selection criteria for hepatic resection in patients with large hepatocellular carcinoma larger than 10 cm in diameter. J Am Coll Surg. 2002;194(5):592-602.
9. Liau KH, Ruo L, Shia J, et al. Outcome of partial hepatectomy for large (> 10 cm) hepatocellular carcinoma. Cancer. 2005;104(9):1948-1955.
10. Kokudo T, Hasegawa K, Matsuyama Y, et al. Survival benefit of liver resection for hepatocellular carcinoma associated with portal vein invasion. J Hepatol. 2016;65(5):938-943.
11. Kokudo T, Hasegawa K, Matsuyama Y, et al. Liver resection for hepatocellular carcinoma associated with hepatic vein invasion: A Japanese nationwide survey. Hepatology. 2017;66(2):510-517.
12. Saeki I, Yamasaki T, Maeda M, et al. Treatment strategies for advanced hepatocellular carcinoma: Sorafenib vs hepatic arterial infusion chemotherapy. World J Hepatol. 2018;10(9):571-584.
13. Shimamura T, Akamatsu N, Fujiyoshi M, et al. Expanded living-donor liver transplantation criteria for patients with hepatocellular carcinoma based on the Japanese nationwide survey: the 5-5-500 rule - a retrospective study. Transpl Int. 2019;32(4):356-368.
14. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378-390.
15. Bruix J, Qin S, Merle P, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial [published correction appears in Lancet. 2017 Jan 7;389(10064):36]. Lancet. 2017;389(10064):56-66.
16. Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163-1173.
17. Zhu AX, Kang YK, Yen CJ, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(2):282-296.
18. Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N Engl J Med. 2018;379(1):54-63.
19. Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020;382(20):1894-1905.
20. Matsuki R, Kawai K, Suzuki Y, et al. Pathological Complete Response in Conversion Hepatectomy Induced by Lenvatinib for Advanced Hepatocellular Carcinoma. Liver Cancer. 2020;9(3):358-360.