Subclassification of patients with intermediate-stage (Barcelona Clinic Liver Cancer stage-B) hepatocellular carcinoma using the up-to-seven criteria and serum tumor markers

Intermediate-stage [Barcelona Clinic Liver Cancer stage-B (BCLC-B)] hepatocellular carcinoma (HCC) comprises of a heterogeneous population of patients with a wide range of tumor burdens. We therefore formulated a subclassification of BCLC-B HCC using the up-to-seven criteria and tumor markers according to the results of a retrospective analysis of these patients. This study included 125 patients newly diagnosed with BCLC-B HCC who underwent transarterial chemoembolization. Among them, 39 and 86 were within or beyond the up-to-seven criteria, respectively. Multivariate Cox proportional hazards analysis was performed to investigate factors that contributed to better prognosis associated with the criteria. Cumulative overall survival (OS) and disease-free survival rates were significantly higher for patients within the up-to-seven criteria compared with those beyond (p = 0.034 and p = 0.001, respectively). Multivariate analysis revealed that low concentrations of des-gamma-carboxy prothrombin (DCP) (< 150 mAU/ml) and alpha-fetoprotein (AFP) (< 100 ng/ml) were independent contributors to better OS of patients within or beyond the up-to-seven criteria, respectively. Accordingly, the patients were classified as follows: group A (patients within the up-to-seven criteria with DCP < 150 mAU/ml), group C (patients beyond the up-to-seven criteria with AFP ae100 ng/ml), and group B (other patients). OS differed significantly among groups (p < 0.001), and the median survival times of group A, B, and C were 4.2, 2.7, and 1.5 years, respectively. The subclassification system incorporating the up-to-seven criteria combined with DCP and AFP levels may serve as better predictors of prognosis that may guide efforts to improve treatment strategies.