Prognosis of Early-Stage Hepatocellular Carcinoma: The Clinical Implications of Substages of Barcelona Clinic Liver Cancer System Based on a Cohort of 1265 Patients

Abstract

The prognostic implication of Barcelona Clinic Liver Cancer (BCLC) substages in Asian patients with hepatocellular carcinoma (HCC) is still obscure.The aim to this study is to compare the prognoses among HCC patients in different substages of the BCLC stage 0 and A.We enrolled 1265 treatment-naive HCC patients with BCLC stage 0 or A from 2007 to 2014. Factors in terms of prognoses were analyzed by multivariate analysis.There were 184, 446, 271, 92, and 272 patients in substage 0, A1, A2, A3, and A4, respectively. After a median follow-up period of 21.0 months, patients in stages 0 and A1 had comparable prognoses (P = 0.136). Both of them had significantly higher overall survival rates than those in stages A2-A4 (all P < 0.001). Multivariate analysis revealed that the factors associated with mortality were serum albumin ≤3.5 g/dL (hazard ratio [HR] 1.459), alpha-fetoprotein >20 ng/mL (HR 1.863), tumor size >3 cm (HR 1.542), BCLC stage A2-A4 (HR 1.488), and treatment modality. Surgical resection had the highest overall survival rate followed by radiofrequency ablation (RFA) (HR 1.598), transarterial chemoembolization (HR 2.224), and other treatments (HR 3.707). Verus patients receiving RFA, those who underwent resection had a higher overall survival rate and lower recurrence rate especially in BCLC stages A2-A4.The BCLC-staging system provided good prognostic stratification for early-stage HCC. Patients with a single tumor >2 cm but without portal hypertension or jaundice had similar prognosis to those in BCLC stage 0. Curative therapies-especially hepatic resection-are suggested in early-stage HCC.

FIGURE 1

The study flow chart.

FIGURE 2

Comparison of cumulative overall survival rates stratified by BCLC substage and treatment modality. (A) Patients in the stage 0 or A1 group had a significantly higher overall survival rate than those in the other substages (all P < 0.001). BCLC 0 versus A1 (P = 0.136) had comparable overall survival rates. (B) The overall survival rates were higher in the BCLC stage 0–A1 group than that in the BCLC stage A2–A4 group (P < 0.001). (C) Patients who underwent resection surgery had the highest overall survival rates than the other groups (all P < 0.001). (D) For patients in BCLC stage 0–A1 group, RFA and resection had comparable overall survival rates (P = 0.465); both of them were significantly better than other treatment modalities. (E) For patients in BCLC stage A2–A4, patients who underwent resection had the highest overall survival rates than other treatment modalities including RFA. BCLC = Barcelona Clinic Liver Cancer, RFA = radiofrequency ablation therapy.

FIGURE 3

Comparison of overall survival rates among different BCLC substages with the same treatment modality. (A) In the resection surgery group, patients in the stage 0–A1 group had a comparable overall survival rate with those in the stage A2–A4 (P = 0.148). (B) In the RFA group, patients in the stage 0–A1 group had a significantly higher overall survival rate than those in the stage A2–A4 (P < 0.001). (C) In the TACE group, patients in the stage 0–A1 group had a higher overall survival rate than those in the stage A2–A4 (P = 0.035). (D) For those underwent other therapy modalities, patients in the stage 0–A1 group had a comparable overall survival rate with their counterpart (P = 0.399). BCLC = Barcelona Clinic Liver Cancer, RFA = radiofrequency ablation therapy, TACE = transarterial chemoembolization.

FIGURE 4

Comparison of overall survival and recurrence rates between RFA and resection surgery for HCC stratified by BCLC substage. In a total cohort, patients who underwent resection had a higher overall survival rate (A, P < 0.001) and lower rate of recurrence (B, P < 0.001) versus those receiving RFA. For BCLC stage 0–A1 HCC patients, there was no statistical significance between RFA and resection in overall survival (C, P = 0.465); resection did have a trend of lower incidence of recurrence versus RFA (D, P = 0.085). Among the BCLC stage A2–A4 patients, the resection group had a better prognoses than the RFA group both in term of overall survival (E, P = 0.006) and recurrence (F, P = 0.045). BCLC = Barcelona Clinic Liver Cancer, HCC = hepatocellular carcinoma, RFA = radiofrequency ablation therapy.