The Prognosis of Single Large Hepatocellular Carcinoma Was Distinct from Barcelona Clinic Liver Cancer Stage A or B: The Role of Albumin-Bilirubin Grade

Abstract

Background/aims: Whether single large hepatocellular carcinoma (SLHCC) is classified as Barcelona Clinic Liver Cancer (BCLC) stage A or B is still controversial. We aimed to compare the clinical manifestations, treatment modalities, and prognoses among patients with SLHCC and those in BCLC stage A and B.

Methods: We enrolled 2,285 treatment-naive hepatocellular carcinoma (HCC) patients with BCLC stage A or B from October 2007 to December 2015. Factors in terms of prognoses were analyzed by multivariate analysis.

Results: We enrolled 1,210, 466, and 609 patients in a BCLC-A, SLHCC, and BCLC-B group, respectively. After a median follow-up duration of 21.2 months, 898 patients had died. The cumulative 5-year survival rates were 57.0, 42.6, and 27.3% for patients in the BCLC-A, SLHCC, and BCLC-B groups, respectively, which were significantly different (p < 0.001). Multivariate analysis indicated that the following independent risk factors were associated with poor prognosis: age > 65 years, alkaline phosphatase > 100 U/L, creatinine > 1.0 mg/dL, alpha-fetoprotein > 20 mg/mL, noncurative treatment, albumin-bilirubin (ALBI) grade, and HCC staging. Subgroup analysis also confirmed that patients in the SLHCC group had a survival rate intermediate to those in the BCLC-A and BCLC-B groups. However, for patients in the SLHCC group and with ALBI grade 1, outcomes were close to those in the BCLC-A group, especially in the setting of curative treatment. For those with ALBI grades 2 or 3, the prognoses were similar to those of the SLHCC and BCLC-B groups.

Conclusion: Patients in the SLHCC group had an overall survival rate intermediate to those of the BCLC-A and BCLC-B groups. It is suggested that the SLHCC group could be classified as occupying a different stage from the BCLC stages A and B. The ALBI grade could help to stratify SLHCC into a different prognostic group. However, the results need to be validated externally in other regions of the world.

Keywords: Barcelona Clinic Liver Cancer stage; Hepatocellular carcinoma; Prognosis; Staging; Tumor size.

Fig. 1

Study flowchart. BCLC, Barcelona Clinic Liver Cancer; HCC, hepatocellular carcinoma; LT, liver transplantation; RFA, radiofrequency ablation; SLHCC, single large hepatocellular carcinoma; TACE, transarterial chemoembolization.

Fig. 2

a Comparison of cumulative OS rates among BCLC stage A, SLHCC, and BCLC stage B stratified by HCC stage. b The same analysis after excluding patients who underwent liver transplantation. c–e Comparison of OS among the three groups of patients in stratified analysis by forest plot: BCLC stage A versus SLHCC (c), SLHCC versus BCLC stage B (d), and BCLC stage A versus stage B (e). AFP, alpha-fetoprotein; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BCLC, Barcelona Clinic Liver Cancer; EVs, esophageal varices; HBsAg, hepatitis B virus surface antigen; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; OS, overall survival; PT/INR, prothrombin time/international normalized ra tio; SLHCC, single large hepatocellular carcinoma.

Fig. 3

Comparison of OS rates among the BCLC-A, SLHCC, and BCLC-B groups stratified by ALBI grade and treatment modality. a ALBI grade 1. b ALBI grade 2. c ALBI grade 3. d Curative treatment. e TACE. f Other treatments. ALBI, albumin-bilirubin; BCLC, Barcelona Clinic Liver Cancer; OS, overall survival; SLHCC, single large hepatocellular carcinoma; TACE, transarterial chemoembolization.

Fig. 4

Interaction between ALBI grade and treatment modalities in determining HCC prognosis. a ALBI grade 1 and curative treatment. b ALBI grade 1 and noncurative treatment. c ALBI grade 2 or 3 and curative treatment. d ALBI grade 2 or 3 and noncurative treatment. ALBI, albumin-bilirubin; BCLC, Barcelona Clinic Liver Cancer; HCC, hepatocellular carcinoma; SLHCC, single large hepatocellular carcinoma.

Fig. 5

Comparison of OS rates between patients with a tumor size between 5 and 10 cm and those with a tumor size > 10 cm in the SLHCC group stratified by treatment modalities. a All patients (p = 0.001). b Patients with curative treatment (p = 0.012). c Patients with noncurative treatment (p = 0.127). OS, overall survival; SLHCC, single large hepatocellular carcinoma.

Fig. 6

Comparison of OS rates between patients with curative treatment and those with noncurative treatment in the SLHCC group stratified by tumor size and ALBI grade. a All patients (p < 0.001). b Tumor size between 5 and 10 cm (p < 0.001). c Tumor size > 10 cm (p < 0.001). d ALBI grade 1 (p = 0.001). e ALBI grade 2 or 3 (p < 0.001). ALBI, albumin-bilirubin; OS, overall survival; SLHCC, single large hepatocellular carcinoma.

Fig. 7

Comparison of OS rates between patients who underwent resection surgery and TACE in the SLHCC group stratified by tumor size and ALBI grade. a All patients (p < 0.001). b Tumor size between 5 and 10 cm (p < 0.001). c Tumor size > 10 cm (p = 0.055). d ALBI grade 1 (p = 0.009). e ALBI grade 2 or 3 (p < 0.001). ALBI, albumin-bilirubin; OS, overall survival; SLHCC, single large hepatocellular carcinoma; TACE, transarterial chemoembolization.