Validation and modification of a proposed substaging system for patients with intermediate hepatocellular carcinoma

Background and Aim: Based on up-to-seven criteria and Child-Pugh score, four substages of Barcelona Clinic Liver Cancer (BCLC) intermediate hepatocellular carcinoma (HCC) were proposed. The purpose of this study was to validate and modify this proposal. Methods: Between January 2002 and February 2011, newly diagnosed intermediate HCC patients underwent transarterial embolization (TAE) were enrolled. Patients were stratified into four (B1-B4) substages and followed up until death or end of 2012. Patients' survivals and discriminatory ability of substaging systems were compared. Results: Five-hundred and eighty patients were enrolled. There were 56.6%, 33.8%, 7.4%, and 2.2% in substage B1, B2, B3, and B4. The 5-year survival rate was 21.4%, 13.9%, 7.4%, and 7.7% with median survival time of 2.4, 1.3, 0.5, and 0.8 years (P<0.001). In addition to substage B1-B4, α-fetoprotein (AFP) level was an independent factor associated with survival in multivariate analysis. According to AFP < or >200ng/mL, B1 was classified into B1a and B1b, and B2 into B2a and B2b. There were no differences in survivals between B1b and B2a (P=0.174), and B2b and B3 (P=0.785). Patients were re-classified into modified (m)B1 (B1a), mB2 (B1b+B2a), mB3 (B2b+B3). The modified substages (mB1-mB3) showed a more desirable substaging system. Conclusions: For BCLC intermediate HCC patients, substages B1-B4 were useful in predicting survival after TAE. However, modified substaging system provided better prognostic prediction.