Prediction of Prognosis of Intermediate-Stage HCC Patients: Validation of the Tumor Marker Score in a Nationwide Database in Japan

Atsushi Hiraoka; Kojiro Michitaka; Takashi Kumada; Namiki Izumi; Masumi Kadoya; Norihiro Kokudo; Shoji Kubo; Yutaka Matsuyama; Osamu Nakashima; Michiie Sakamoto; Tadatoshi Takayama; Takashi Kokudo; Kosuke Kashiwabara; Susumu Eguchi; Tatsuya Yamashita; Masatoshi Kudo

doi:10.1159/000495944

Prediction of Prognosis of Intermediate-Stage HCC Patients: Validation of the Tumor Marker Score in a Nationwide Database in Japan

Liver Cancer. 2019 Oct;8(5):403-411. doi: 10.1159/000495944. Epub 2019 Feb 18.

Authors

Atsushi Hiraoka¹, Kojiro Michitaka¹, Takashi Kumada², Namiki Izumi³, Masumi Kadoya⁴, Norihiro Kokudo⁵, Shoji Kubo⁶, Yutaka Matsuyama⁷, Osamu Nakashima⁸, Michiie Sakamoto⁹, Tadatoshi Takayama¹⁰, Takashi Kokudo¹¹, Kosuke Kashiwabara¹², Susumu Eguchi¹³, Tatsuya Yamashita¹⁴, Masatoshi Kudo¹⁵

Affiliations

¹ Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.
² Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan.
³ Department of Gastroenterology, Musashino Red Cross Hospital, Tokyo, Japan.
⁴ Department of Radiology, Shinshu University School of Medicine, Matsumoto, Japan.
⁵ National Center for Global Health and Medicine, Tokyo, Japan.
⁶ Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
⁷ Department of Biostatistics, School of Public Health, University of Tokyo, Tokyo, Japan.
⁸ Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan.
⁹ Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
¹⁰ Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan.
¹¹ Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
¹² Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
¹³ Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
¹⁴ Advanced Preventive Medical Research Center, Kanazawa University, Kanazawa, Japan.
¹⁵ Department of Gastroenterology and Hepatology, Kindai University School of Medicine, Osaka, Japan.

Abstract

Background/aim: Adequate assessment of transcatheter arterial chemoembolization (TACE)-refractory status has become more important for switching treatment in intermediate-stage (BCLC-B) hepatocellular carcinoma (HCC) patients treated with TACE. The usefulness of a previously proposed tumor marker score for predicting prognosis of BCLC-B HCC patients treated with TACE was investigated.

Methods: Using a nationwide database, we examined the records of 1,306 naïve BCLC-B HCC with Child-Pugh A who were treated from 2001 to 2007, after excluding those with missing data (hepatic function or tumor markers) or cases with a single large tumor. Alpha-fetoprotein (AFP) ≥100 ng/mL, fucosylated AFP (AFP-L3) ≥10%, and des-gamma-carboxy prothrombin ≥100 mAU/mL were markers used to define positive cases. The number of positive tumor markers was used as a prognostic score, and its predictive value was evaluated in a retrospective manner.

Results: Median survival time became shorter along with increased score (0, 1, ≥2 = 4.8, 3.8, 3.2 years, respectively; p < 0.01). Tumor marker score (≥2; hazard ratio [HR] 1.675, 95% confidence interval [CI] 1.372-2.044, p < 0.001), serum levels of albumin (≥3.5 g/dL; HR 0.726, 95% CI 0.528-0.997, p = 0.048), and up-to-7 criteria (HR 1.673, 95% CI 1.400-2.000, p < 0.001) were significant prognostic factors for death in the Cox hazard multivariate analysis.

Conclusion: Tumor marker score had a useful predictive prognostic value in BCLC-B HCC treated with TACE. Especially in patients with a tumor marker score of 2 or greater, a poor therapeutic response should be expected, and appropriate judgement of TACE-refractory status is necessary.

Keywords: Alpha-fetoprotein; BCLC-B; Des-gamma-carboxy prothrombin; Fucosylated alpha-fetoprotein; Hepatocellular carcinoma; Prognosis; TACE-refractory status.