Prognostic value of preoperative serum tumor markers in gastric cancer

Table 1 Previous studies reporting the association between preoperative tumor markers and oncologic outcomes

Ref.	CEA	CA199	CA50	Number of	Prognostic impact in overall survival (P value)
	cut-off value	cut-off value	cut-off value	patients	Univariate analysis			Multivariate analysis
	(ng/mL)	(U/mL)	(U/mL)		CEA	CA19-9	CA50	CEA	CA19-9	CA50
Ishigami et al[10]	10	74	NA	549	< 0.0001	< 0.0001		0.040	0.150
Nakane et al[18]	10	NA	NA	865				0.001
Kochi et al[6]	5	37	NA	434	< 0.01	< 0.01		0.044	0.169
Schauer et al[11]	NA	45	NA	120		0.007
Marrelli et al[7]	5	37	NA	153	< 0.0005	< 0.0001		< 0.05	< 0.05
Park et al[8]	7	NA	NA	810	< 0.001			0.005
1Liu et al[12]	10	37	20	273	0.000	0.000	0.000	0.000	0.000	0.006
Liu et al[13]	10	35	25	391	0.000	0.000	0.001	0.006	> 0.05	> 0.05
Gaspar et al[23]	5	35	NA	82				0.770	0.630
Ucar et al[19]	5	35	NA	95				0.500	0.600
Tachibana et al[14]	5	NA	NA	196	< 0.0001			0.000
Duraker et al[15]	5	37	NA	168	0.003	0.014		0.145	0.174
Tocchi et al[16]	3	37	NA	59	< 0.03	< 0.05		0.000	0.014
Lai et al[9]	5	37	NA	196				0.867	0.230
Dilege et al[17]	5	33	NA	75	> 0.05	> 0.05

¹Prognostic significance of tumor markers in T4a gastric cancer. NA: Not available; CEA: Carcinoembryonic antigen; CA: Carbohydrate antigen.

Table 2 Correlation between tumor makers and major clinicopathologic characteristics of 363 patients with gastric cancer n (%)

Patient characteristics	Cases	CEA (+)	P	CA19-9 (+)	P	CA50 (+)	P
Age (yr)			< 0.001		0.213		0.134
< 60	169 (46.6)	26 (15.4)		36 (21.7)		40 (28.4)
≥ 60	194 (53.4)	61 (31.4)		31 (16.5)		31 (20.8)
Gender			0.022		0.800		0.375
Male	266 (73.3)	72 (27.1)		48 (18.6)		48 (23.1)
Female	97 (26.7)	15 (15.5)		19 (19.8)		23 (28.0)
Tumor size (cm)			0.007		0.042		0.051
< 6	243 (66.9)	48 (19.8)		38 (16.0)		40 (20.9)
≥ 6	120 (33.1)	39 (32.5)		29 (25.0)		31 (31.3)
Tumor location			0.463		0.737		0.662
Cardia or fundus	117 (33.1)	33 (28.2)		21 (18.6)		20 (22.0)
Corpus or angulus	131 (37.1)	31 (23.7)		22 (17.2)		26 (25.2)
Antrum	103 (29.2)	21 (20.4)		22 (21.8)		24 (28.2)
Whole stomach	2 (0.6)	1 (50.0)		0 (0.0)		0 (0.0)
Differentiation			0.65		0.671		0.701
Well/moderate	61 (16.8)	16 (26.2)		10 (16.9)		10 (22.2)
Poorly	302 (83.2)	71 (23.5)		57 (19.3)		61 (24.9)
T category			0.018		0.058		0.308
pT1-pT2	48 (13.2)	5 (10.4)		4 (8.7)		7 (17.9)
pT3-pT4	315 (86.8)	82 (26.0)		63 (20.5)		64 (25.5)
N category			0.109		< 0.001		0.001
pN0	61 (16.8)	14 (23.0)		10 (16.7)		10 (21.3)
pN1	73 (20.1)	10 (13.7)		5 (6.9)		10 (16.9)
pN2	100 (27.5)	29 (29.0)		12 (12.5)		10 (13.5)
pN3	129 (35.5)	34 (26.4)		40 (31.7)		41 (37.3)
Vascular/nerves invasion			0.997		0.950		0.763
Negative	171 (47.1)	41 (24.0)		31 (18.8)		30 (23.6)
Positive	192 (52.9)	46 (24.0)		36 (19.0)		41 (25.2)
AJCC stage			0.347		0.084		0.187
I	2 (0.6)	0 (0.0)		0 (0.0)		0 (0.0)
II	97 (26.7)	19 (19.6)		11 (11.7)		13 (17.6)
III	264 (72.7)	68 (25.8)		56 (21.7)		58 (27.1)

AJCC: American Joint Committee on Cancer; CEA: Carcinoembryonic antigen.

Table 3 Univariate model for disease-free survival and overall survival by log-rank test

Tumor markers	DFS (P)	OS (P)
CEA (+)	0.197	0.023
CA19-9 (+)	0.236	0.009
CA50 (+)	0.335	0.004
CEA (+) and CA19-9 (+)	0.236	0.026
CA50 (+) and CEA (+)	0.236	0.100
CA19-9 (+) and CA50 (+)	0.236	0.021
CEA (+) and CA19-9 (+) and CA50 (+)	0.397	0.751
CEA (+) or CA19-9 (+) or CA50 (+)	0.302	0.002

CEA: Carcinoembryonic antigen; CA: Carbohydrate antigen; DFS: Disease-free survival; OS: Overall survival.

Table 4 Univariate model for disease-free survival and overall survival by log-rank test when considering the adjuvant chemotherapy

Tumor	DFS (P)		OS (P)
markers	Adjuvant chemotherapy	Non-adjuvant chemotherapy	Adjuvant chemotherapy	Non-adjuvant chemotherapy
CEA (+)	0.878	0.116	0.297	0.017
CA19-9 (+)	0.961	0.116	0.179	< 0.001
CA50 (+)	0.828	0.182	0.069	0.001
CEA (+) and CA19-9 (+)	0.961	0.116	0.304	0.004
CA50 (+) and CEA (+)	0.991	0.132	0.383	0.065
CA19-9 (+) and CA50 (+)	0.991	0.132	0.303	< 0.001
CEA (+) and CA19-9 (+) and CA50 (+)	0.991	0.132	0.867	0.298
CEA (+) or CA19-9 (+) or CA50 (+)	0.742	0.196	0.107	< 0.001

CEA: Carcinoembryonic antigen; CA: Carbohydrate antigen; DFS: Disease-free survival; OS: Overall survival.

Table 5 Independent prognostic factors for predicting disease-free survival and overall survival by multivariate analysis using Cox model

Factors	DFS			OS
	HR	95%CI	P	HR	95%CI	P
Age	1.028	0.825-1.770	0.331	0.932	0.667-1.303	0.682
Gender	1.072	0.634-1.814	0.795	0.791	0.543-1.151	0.220
Tumor size	1.718	1.159-2.546	0.007	1.998	1.433-2.785	< 0.001
Differentiation	1.398	0.685-2.853	0.357	0.714	0.398-1.281	0.258
T category	0.796	0.213-2.978	0.734	6.042	2.190-16.668	0.001
N category	1.014	0.836-1.231	0.884	1.734	1.429-2.014	< 0.001
Vascular/nerves invasion	0.930	0.606-1.426	0.739	1.515	1.045-2.195	0.028
Adjuvant chemotherapy	0.931	0.614-1.411	0.736	0.618	0.425-0.898	0.012
CEA	3.045	0.401-23.157	0.282	0.902	0.618-1.316	0.592
CA19-9	0.392	0.045-3.384	0.394	0.836	0.449-1.556	0.571
CA50	1.058	0.546-2.050	0.868	1.470	0.842-2.569	0.176

CEA: Carcinoembryonic antigen; CA: Carbohydrate antigen; DFS: Disease-free survival; OS: Overall survival.

Table 6 Multivariate analysis of overall survival of patients without chemotherapy

Factors	OS
	HR	95%CI	P
Age	1.525	0.765-3.041	0.230
Gender	1.229	0.559-2.701	0.608
Tumor size	4.758	2.339-9.678	< 0.001
Differentiation	0.784	0.259-2.379	0.668
T category	4.566	0.570-36.569	0.153
N category	2.096	1.506-2.916	< 0.001
Vascular/nerves invasion	2.861	1.247-6.566	0.013
CEA	1.329	0.670-2.637	0.415
CA19-9	5.077	1.203-21.427	0.027
CA50	0.671	0.183-2.463	0.547

CEA: Carcinoembryonic antigen; CA: Carbohydrate antigen; OS: Overall survival.