Barcelona clinic liver cancer-stage C hepatocellular carcinoma: A novel approach to subclassification and treatment

Abstract

Barcelona clinic liver cancer-stage C (BCLC-C) encompasses a broad spectrum of tumor burdens, liver function statuses, patient prognoses, and treatment strategies. Currently, sorafenib is the only recommended treatment for patients with BCLC-C and outcomes remain suboptimal. The aims of this study were to assess the heterogeneity of BCLC-C hepatocellular carcinoma (HCC) cases, propose a novel subclassification for these cases, and suggest optimal treatment strategies other than sorafenib.We retrospectively analyzed 196 consecutive BCLC-C HCC patients who were diagnosed and treated between January 2008 and December 2015.All 196 patients were classified according to the modified Union for International Cancer Control (Stage I, 0.0%; Stage II, 8.2%; Stage III, 64.3%; Stage IVA, 21.9%; and Stage IVB, 5.6%) and American Joint Committee on Cancer TNM staging systems (Stage I, 0.0%; Stage II, 16.3%; Stage IIIA, 27.6%; Stage IIIB, 49.5%; Stage IIIC, 1.5%; Stage IVA, 1.0%; and Stage IVB, 4.1%). First-line treatment modalities included surgical resection (8.7%), transarterial chemoembolization (49.5%), hepatic arterial infusion therapy (5.6%), sorafenib therapy (9.2%), radiotherapy (9.2%), and best supportive care (10.7%). In univariate analysis, Child-Pugh score, tumor size, distant metastasis, multinodular or infiltrative/diffuse type of HCC, main portal vein invasion, hepatic vein invasion, and bile duct invasion were significantly associated with survival (P < .001). Tumor size, distant metastasis, HCC type, and bile duct invasion remained significantly associated with 1-, 3-, and 5-year survival rates in multivariate Cox regression analyses. Using these 4 characteristics, a novel subclassification of BCLC-C was developed and applied to the patient cohort. The subclassification included 5 substages (stages C0-C4), as defined based on the number of characteristics that were present in each HCC case (0-4). The subclassification showed significant associations with survival, with median survival times of 3026 days, 605 days, 224 days, 126 days, and 82 days for patients with Stage C0, C1, C2, C3, and C4 disease, respectively (P < .001). Additionally, diverse survival rates were observed when different treatment modalities were selected for cases within each substage.The proposed BCLC-C subclassification of HCC patients is effective in providing better prognostic subclassifications and more appropriate treatment strategies.

Figure 1

Kaplan-Meier curves of 5-year survival rates after diagnosis stratified according to (A) tumor size (log-rank test; P < .001), (B) distant metastasis (log-rank test; P < .001), (C) bile duct invasion (log-rank test; P < .001), and (D) nodularity (log-rank test; P < .05).

Figure 2

(A) Kaplan-Meier curve of 5-year survival rates of 196 enrolled patients. (B) Kaplan-Meier curve of 5-year survival rates after diagnosis stratified according to the Barcelona Clinic Liver Cancer-Stage C subclassification (Cox regression analysis; P < .001).

Figure 3

Patient numbers and median overall survival (OS) stratified according to the BCLC-C classification. BCLC-C = Barcelona Clinic Liver Cancer-Stage C, CNUH = Chonnam National University Hospital, CNUHH = Chonnam National University Hospital Hwasun, HCC = hepatocellular carcinoma, OS = overall survival.