Selecting an Optimal Staging System for Intermediate-Stage Hepatocellular Carcinoma: Comparison of 9 Currently Used Prognostic Models

Yong-Fa Zhang,1,2,* Ming Shi,3,* Liang-He Lu,3 Lu Wang,1,2 Rong-Ping Guo3 1Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China; 3The Department of Hepatobiliary Oncology of Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lu WangDepartment of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of ChinaTel/Fax +8620-64175590Email cms024mm@163.comRong-Ping GuoDepartment of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People’s Republic of ChinaTel/Fax +8620-87342266Email guorp@sysucc.org.cnPurpose: It remains unknown which staging system is best in predicting the survival of patients with intermediate stage hepatocellular carcinoma (HCC). We aimed to investigate the performance of nine currently used HCC staging systems.Patients and Methods: Between 2005 and 2014, a large cohort of 880 consecutive patients with intermediate stage HCC and sufficient data for utilization in all staging systems were enrolled. The prognostic performance of each staging system was compared. Independent prognostic variables were also identified.Results: Multivariate analysis revealed that alkaline phosphatase (ALP), aspartate aminotransferase (AST), etiology, alpha-fetoprotein (AFP), Child-Pugh stage, tumor size, and tumor number were independent prognostic factors for survival. In the entire cohort, the Hong Kong Liver Cancer (HKLC) staging system was associated with the highest Harrell’s c-index and lowest Akaike information criterion value in comparison with other systems. In subgroup analysis according to treatment strategy, the HKLC staging system remained the best prognostic model in patients undergoing hepatic resection (n=222) or transarterial chemoembolization (n=658). Additional prognostic factors of AST, ALP, etiology, and AFP improved the discriminatory ability of HKLC.Conclusion: The HKLC staging system is stable and consistently the best prognostic model in all patients with intermediate-stage HCC and in patients subjected to different treatment strategies. Selecting an optimal staging system is helpful in improving the design of future clinical trials in intermediate stage HCC.Keywords: hepatocellular carcinoma, intermediate-stage, staging system, prognosis, overall survival, hepatic resection, transarterial chemoembolization