Postoperative outcomes and recurrence patterns of intermediate-stage hepatocellular carcinoma dictated by the sum of tumor size and number

Table 1 Characteristics of patients with Barcelona Clinic Liver Cancer stage A or B multinodular hepatocellular carcinoma, n (%)

Variables	Total (n = 143)	BCLC-A (n = 25)	BCLC-B (n = 118)	P value
Male gender	134 (93.7)	25 (100)	109 (92.4)	0.330
Age (yr)	52.1 ± 12.7	50.5 ± 14.5	52.4 ± 12.4	0.490
BMI	22.97 ± 3.15	23.05 ± 3.35	22.96 ± 3.12	0.895
HBs-Ag positive	131 (91.6)	24 (96)	107 (90.7)	0.635
Albumin (g/L)	38.89 ± 4.51	39.95 ± 5.15	38.65 ± 4.34	0.194
Bilirubin (μmol/L)	13.8 (9.9, 18)	12.9 (10.2, 20.9)	13.9 (9.7, 17.8)	0.568
ALBI grade				0.680
1	69 (48.3)	13 (52)	56 (47.5)
2/3	74 (51.7)	12/0 (48/0)	62/0 (52.5/0)
AFP (μg/L)	239 (13, 2338)	74 (6, 390)	483 (16, 2944)	0.011
Maximum tumor size (cm)	5.6 (3.4, 7.6)	2.5 (2.1, 2.9)	6.2 (4.1, 8.4)	< 0.001
Tumor number				0.460
≤ 3	136 (95.1)	25 (100)	111 (94.1)
> 3	7 (4.9)	0	7 (5.9)
Tumor distribution				0.506
Unilateral	83 (58)	16 (64)	67 (56.8)
Bilateral	60 (42)	9 (36)	51 (43.2)
Presence of microvascular invasion	15 (10.5)	1 (4)	14 (11.9)	0.420
Edmondson-Steiner grade				0.337
I-II	85 (59.4)	17 (68)	68 (57.6)
III-IV	58 (40.6)	8 (32)	50 (42.4)
Major resection	64 (44.8)	4 (16)	60 (50.8)	0.001
Anatomical hepatectomy	22 (15.4)	4 (16)	18 (15.3)	1.000
Preoperative TACE				0.690
No	121 (84.6)	20 (80)	101 (85.6)
Yes	22 (15.4)	5 (20)	17 (14.4)

BMI: Body mass index; HBs-Ag: Hepatitis B surface antigen; ALBI: Albumin-bilirubin; AFP: Alpha-fetoprotein; IQR: Interquartile range; TACE: Transarterial chemoembolization.

Table 2 Univariate and multivariate analysis of overall survival in patients with Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma

Variables	Univariate analysis		Multivariate analysis
	HR (95%CI)	P value	HR (95%CI)	P value
Gender (male)	1.128 (0.409-3.117)	0.816
Age (> 65 yr)	0.668 (0.285-1.562)	0.352
BMI > 25	0.954 (0.513-1.772)	0.880
HBs-Ag positive	1.084 (0.466-2.525)	0.851
ALBI grade
1	1.00 (Reference)		1.00 (Reference)
2	1.891 (1.112-3.217)	0.019	2.279 (1.236-4.201)	0.008
AFP > 400 ng/mL	1.969 (1.165-3.327)	0.011
Maximum tumor size > 5 cm	2.510 (1.354-4.651)	0.003
Tumor number > 3	3.806 (1.716-8.444)	0.001	5.519 (2.207-13.803)	< 0.001
N + S > 10	3.403 (2.031-5.702)	< 0.001	2.996 (1.779-5.045)	< 0.001
Bilateral tumor distribution	2.201 (1.312-3.694)	0.003
Presence of MVI	1.816 (0.855-3.858)	0.120
Edmondson-Steiner III-IV	2.084 (1.248-3.480)	0.005	2.051 (1.219-3.449)	0.007
Major resection	1.886 (1.115-3.191)	0.018
NAH	0.905 (0.458-1.788)	0.775
Preoperative TACE
No	1.00 (Reference)
Yes	0.494 (0.198-1.238)	0.132

BMI: Body mass index; HBs-Ag: Hepatitis B surface antigen; ALBI: Albumin-bilirubin; AFP: Alpha-fetoprotein; N + S: The sum of tumor size and number; MVI: Microvascular invasion; NAH: Non-anatomical hepatectomy; TACE: Transarterial chemoembolization.

Table 3 Univariate and multivariate analysis of recurrence-free survival in patients with Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma

Variables	Univariate analysis		Multivariate analysis
	HR (95%CI)	P value	HR (95%CI)	P value
Gender (male)	1.135 (0.526-2.450)	0.747
Age (> 65 yr)	0.881 (0.514-1.511)	0.646
BMI > 25	1.157 (0.729-1.836)	0.536
HBs-Ag positive	1.109 (0.558-2.202)	0.769
ALBI grade
1	1.00 (Reference)
2	1.474 (0.988-2.198)	0.057
AFP > 400 ng/mL	1.458 (0.984-2.162)	0.060
Maximum tumor size > 5 cm	1.253 (0.830-1.891)	0.283
Tumor number > 3	2.449 (1.123-5.343)	0.024
N + S > 10	2.113 (1.385-3.224)	0.001	1.657 (1.057-2.596)	0.028
Bilateral tumor distribution	2.104 (1.409-3.140)	< 0.001	1.820 (1.187-2.791)	0.006
Presence of MVI	1.757 (0.973-3.171)	0.062
Edmondson-Steiner III-IV	1.709 (1.151-2.539)	0.008	1.676 (1.127-2.493)	0.011
Major resection	1.285 (0.867-1.904)	0.211
NAH	1.126 (0.650-1.950)	0.673
Preoperative TACE
No	1.00 (Reference)
Yes	0.784 (0.437-1.405)	0.414

BMI: Body mass index; HBs-Ag: Hepatitis B surface antigen; ALBI: Albumin-bilirubin; AFP: Alpha-fetoprotein; N + S: The sum of tumor size and number; MVI: Microvascular invasion; NAH: Non-anatomical hepatectomy; TACE: Transarterial chemoembolization.