Ascites and alpha-fetoprotein improve prognostic performance of Barcelona Clinic Liver Cancer staging

Table 1 Characteristics of the study population n (%)

	BCLC A	BCLC B
Number	n = 496	n = 564
Age (yr), mean ± SD	56.2 ± 8.3	56.6 ± 8.7
Male	414 (83.5)	452 (80.3)
Cirrhosis	448 (90.5)	510 (90.4)
Ascites	91 (18.3)	151 (26.8)
Etiology of liver disease
HCV	986 (93)	973 (91.8)
HBV	43 (4)	52 (4.9)
Non-HCV, non-HBV	31 (3)	35 (3.3)
AFP (ng/mL), mean (range)	365 (20-12, 660)	890 (20-26, 400)
AFP ≥ 200 (ng/mL)	166 (33.5)	242 (42.9)
Number of tumor nodule
One	404 (81.5)	0
Two	53 (10.7)	204 (36.2)
Three	39 (7.9)	187 (33.1)
More than three	0	173 (30.7)
Size of nodule, mean ± SD	3.9 ± 1.8	7.4 ± 2.7
Child-Pugh
A	268 (54)	261 (46.3)
B	228 (46)	303 (53.7)
Treatment modality
Resection	113 (22.8)	0
Transplantation	7 (1.4)	0
PEI	62 (12.5)	0
RFA	262 (52.8)	0
Microwave ablation	18 (3.6)	0
TACE	34 (6.9)	564 (100)
Biochemical data, mean ± SD
Serum total bilirubin (mg/dL)	1.5 ± 1.3	1.5 ± 1.1
Serum albumin (g/dL)	3.3 ± 0.6	3.3 ± 0.6
International normalized ratio	1.2 ± 0.4	1.2 ± 0.5
ALT (IU/mL)	63 ± 45	62 ± 58
AST (IU/mL)	82 ± 61	83 ± 80

Data are frequency counts (percentage of total) or mean ± SD. AFP: Alpha-fetoprotein; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BCLC: Barcelona Clinic Liver Cancer; RFA: Radiofrequency ablation; PEI: Percutaneous ethanol injection; TACE: Trans-arterial chemoembolization.

Table 2 Patients’ survival according to Barcelona Clinic Liver Cancer, alpha-fetoprotein level and ascites

		1-yr survival	2-yr survival	3-yr survival	Median survival (mo)	P value
BCLC	A (n = 496)	90%	69%	56%	37	< 0.001
	B (n = 564)	69%	33%	18%	19
AFP	< 200 ng/mL (n = 652)	85%	59%	50%	33	< 0.001
	≥ 200 ng/mL (n = 408)	71%	41%	22%	21
Ascites	Absent (n = 818)	83%	58%	44%	31	< 0.001
	Present (n = 242)	69%	29%	23%	19

P < 0.05 is considered significant. AFP: Alpha-fetoprotein; BCLC: Barcelona Clinic Liver Cancer.

Table 3 Univariate analysis of baseline predictors of survival for each stage

Variable		BCLC A			BCLC B
		Number of patients	Median survival (mo)	P value	Number of patients	Median survival (mo)	P value
Age	< 56	250	39	0.590	259	19	0.230
	≥ 56	246	37		305	18
Sex	Male	414	37	0.550	452	18	0.080
	Female	82	39		112	23
Ascites	Absent	405	37	< 0.001	413	2014	< 0.001
	Present	91	22		151
Number of tumor nodules	One	404	37	0.003	0	-	-
	> 1	92	28		564	18
Maximum tumor diameter	≤ 5 cm	454	37	0.700	119	25	< 0.001
	> 5 cm	42	34		445	18
AFP (ng/mL)	< 200	330	37	< 0.001	322	20	< 0.001
	≥ 200	166	28		242	17
CTP class	A	268	39	< 0.001	261	24	< 0.001
	B	228	24		303	15

P-value < 0.05 is considered significant. AFP: Alpha-fetoprotein; BCLC: Barcelona Clinic Liver Cancer; CTP: Child-Turcott-Pugh score.

Table 4 Multivariate analysis of baseline predictors of survival for each stage

Variable	BCLC A		BCLC B
	HR (95%CI)	P value	HR (95%CI)	P value
Number of tumor nodules > 1	1.82 (1.21-2.75)	0.004	-	-
Maximum tumor diameter > 5 cm	1.02 (0.49-2.13)	0.942	2.95 (1.87-4.6)	< 0.001
Elevated Child score	3.2 (2.12-4.87)	< 0.001	1.75 (1.27-2.42)	0.001
AFP ≥ 200 ng/mL	1.6 (1.11-2.32)	0.012	1.3 (1.01-1.74)	0.040
Presence of ascites	1.7 (1.16-2.66)	0.007	1.44 (1.03-2.04)	0.030

P-value < 0.05 is considered significant AFP: Alpha-fetoprotein; BCLC: Barcelona Clinic Liver Cancer; HR: Hazard ratio; CI: Confidence interval.

Table 5 Patients’ survival according to modified Barcelona Clinic Liver Cancer staging system

		1-yr survival	2-yr survival	3-yr survival	Median survival (mo)	P value
BCLC A	No ascites, AFP < 200 ng/mL (n = 280)	93%	77%	70%	39	< 0.001
	Ascites or AFP ≥ 200 ng/mL (n = 175)	84%	59%	36%	30
	Ascites, AFP ≥ 200 ng/mL (n = 41)	83%	23%	23%	19
BCLC B	No ascites, AFP < 200 ng/mL (n = 237)	77%	40%	21%	22
	Ascites or AFP ≥ 200 ng/mL (n = 261)	67%	27%	15%	18
	Ascites, AFP ≥ 200 ng/mL (n = 66)	46%	15%	7%	12

P-value < 0.05 is considered significant. AFP: Alpha-fetoprotein; BCLC: Barcelona Clinic Liver Cancer.