US–Japan Comparison of Hepatocellular Carcinoma Detected Under Surveillance

Background: Differences in outcomes of hepatocellular carcinoma (HCC) between countries have been largely attributed to variation in the conduct of surveillance and subsequent HCC treatment eligibility; however, differences in outcomes among those detected under surveillance have not been well described. We compared characteristics and prognosis between patients with surveillance-detected HCC from the United States (US) and Japan. Methods: Patients in whom initial HCC was detected under surveillance between January 2006 and December 2015 from two centers in the US and two from Japan were included. Survival was compared between patients from the US and Japan using multivariable Cox regression analysis and propensity-score matched analysis. We performed subgroup analyses by liver disease etiology, tumor stage, and type of HCC treatment. Findings: Of 3788 HCC patients, 1797 (47.4%) were diagnosed under surveillance –715 from the US and 1082 from Japan. Patients from the US diagnosed under surveillance had worse liver dysfunction and larger tumor burden than those from Japan. In multivariate analysis, US patients with surveillance-detected HCC had significantly worse survival than those from Japan (HR 1.17, 95%CI 1.00–1.35), which was also observed in propensity-score matched analysis. However, this difference was no longer significant after adjusting for treatment type (HR 1.07, 95%CI 0.92–1.25). When stratified by treatment type, survival was comparable between the two countries except lower survival among patients who underwent resection in the US versus Japan. Interpretation: Prognosis of patients with surveillance-detected HCC is poorer in the US than Japan, primarily driven by differences in treatment delivery. Studies are necessary to elucidate reasons for these differences. Funding Statement: No funding on this study. Dr. Singal’s research is in part supported by U01CA230694. Dr. Parikh’s research is in part supported by U01CA230669. Declaration of Interests: Hidenori Toyoda has received lecturer fees from Gilead Sciences, AbbVie, MSD, and Bayer. Neehar Parikh has served as a consultant for Bristol Myers-Squibb, Exact Sciences, Eli Lilly, Freenome has served on advisory boards of Genentech, Eisai, Bayer, Exelixis, Wako/Fujifilm and has received research funding from Bayer, Target Pharmasolutions, Exact Sciences, and Glycotest. Amit Singal has been on advisory boards and served as a consultant for Wako Diagnostics, Roche, Exact Sciences, Glycotest, Genentech, Bayer, Eisai, BMS, Exelixis, Merck, AstraZeneca, and TARGET Pharmasolutions. The other authors have no conflict of interest. Ethics Approval Statement: This study was conducted after approval by the institutional review board of each participating institutions and was carried out in compliance with the Helsinki Declaration. Written informed consent was waived due to the retrospective nature of this study.