Metastatic lymph nodes and prognosis assessed by the number of retrieved lymph nodes in gastric cancer

Table 1 Clinical and pathological characteristics of patients in the training cohort and validation cohort

Characteristics	Training cohort	Validation cohort	P value
	n = 4968	n = 11154
Sex			< 0.001
Male	3634 (73.1)	7214 (64.7)
Female	1334 (26.9)	3940 (35.3)
Age (yr)			< 0.001
≤ 60	2845 (57.3)	3418 (30.6)
> 60	2123 (42.7)	7736 (69.4)
Tumor location			< 0.001
Upper third	552 (11.1)	3954 (35.4)
Middle third	811 (16.3)	1248 (11.2)
Lower third	3605 (72.6)	5952 (53.4)
Tumor size (mm)			< 0.001
≤ 50	3225 (64.9)	6813 (61.1)
> 50	1743 (35.1)	4341 (38.9)
Histological type			< 0.001
Well -moderately differentiated	2056 (41.4)	3402 (30.5)
Poorly-undifferentiated	2204 (44.4)	4197 (37.6)
Signet ring cell	397 (8.0)	1899 (17.0)
Others	311 (6.3)	1656 (14.8)
pT stage			< 0.001
pT1	1106 (22.3)	2746 (24.6)
pT2	745 (15.0)	1534 (13.8)
pT3	1583 (31.9)	4570 (41.0)
pT4	1534 (30.9)	2304 (20.7)
pN stage			< 0.001
pN0	2062 (41.5)	5411 (48.5)
pN1	927 (18.7)	2039 (18.3)
pN2	893 (18.0)	1768 (15.9)
pN3	1086 (21.9)	1936 (17.4)
pTNM			< 0.001
I	1445 (29.1)	3476 (31.2)
II	1383 (27.8)	3821 (34.3)
III	2140 (43.1)	3857 (34.6)
RLNs, median (range)	27 (1-95)	16 (1-90)
Chemotherapy			< 0.001
No/unknown	3769 (75.9)	5191 (46.5)
Yes	1199 (22.5)	5963 (53.5)

Tumor location, tumor size, pTNM stage, histological type and the number of removed lymph nodes were determined according to the postoperative pathology report. Statistically significant P values are in bold (P < 0.05).

RLNs: Retrieved lymph nodes.

Table 2 Five-year overall survival by the number of retrieved lymph nodes in the training cohort

pT stage	No. of retrieved lymph nodes														P value
	1-5 (No., %)		6-15 (No., %)		16-25 (No., %)		26-35 (No., %)		36-45 (No., %)		46-55 (No., %)		55 + (No., %)
pT1	20	90.0	223	89.1	403	92.5	303	94.4	110	91.0	31	100.0	16	100.0	0.210
pT2	3	66.7	86	82.1	280	84.3	223	86.4	98	91.3	39	87.1	11	100.0	0.371
pT3	4	50.0	148	70.0	486	64.8	531	61.7	267	60.3	98	62.4	42	48.5	0.172
pT4	3	33.3	124	45.9	439	51.0	460	58.3	296	55.2	135	67.4	77	56.1	0.005

No: The number of patients. The five-year overall survival rate is presented as %.

Table 3 Chi-square analysis of the number of removed lymph nodes and patient characteristics in the pT1-pT4 subgroups in the Chinese training cohort

Characteristics	pT1 (1106), RLNs			P value	pT2 (745), RLNs			P value	pT3 (1583), RLNs			P value	pT4 (1534), RLNs			P value
	≤ 12	13-25	≥ 26		≤ 17	18-30	≥ 31		≤ 19	20-38	≥ 39		≤ 16	17-44	≥ 45
Sex				0.114			0.803					0.006				0.132
Male	112	353	320		109	274	188		230	677	240		119	851	161
Female	31	150	140		32	80	62		73	295	68		43	286	74
Age (yr)				< 0.001				0.699				0.002				0.273
≤ 60	74	302	323		80	214	152		137	523	183		82	637	138
> 60	69	201	137		61	140	98		166	449	125		80	500	97
Tumor location				0.003				0.216				0.036				0.025
Upper third	17	24	19		17	34	15		54	139	36		34	137	26
Middle third	14	59	68		17	40	37		63	164	68		25	211	45
Lower third	112	420	373		107	280	198		186	669	204		103	789	164
Tumor size (mm)				0.005				0.004				< 0.001				< 0.001
≤ 50	139	477	417		129	287	196		202	514	147		87	549	81
> 50	4	26	43		12	67	54		101	458	161		75	588	154
Histological type				0.008				0.689				0.878				0.145
Well-moderately differentiated	67	273	229		67	160	104		125	378	116		73	391	73
Poorly-undifferentiated	39	153	158		63	148	113		122	426	141		75	631	135
Signet ring cell	14	36	43		6	24	17		36	113	32		7	57	12
Others	23	41	30		5	22	16		20	55	19		7	58	15
pN stage				< 0.001				0.128				< 0.001				< 0.001
pN0	125	43	374		85	195	127		112	241	62		54	220	37
pN1	15	49	45		32	80	57		86	206	54		41	240	22
pN2	3	22	28		21	50	40		68	237	64		42	275	43
pN3	0	2	13		3	29	26		37	288	128		25	402	133
pTNM				0.014				0.045				< 0.001				0.003
I	140	479	419		85	195	127		0	0	0		0	0	0
II	3	24	40		53	130	97		198	447	116		43	201	31
III	0	0	1		3	29	26		105	525	192		119	936	204

Tumor location, tumor size, pTNM stage, histological type and the number of removed lymph nodes were determined according to the postoperative pathology report. Statistically significant P values are in bold (P < 0.05).

RLNs: Retrieved lymph nodes.

Table 4 Chi-square analysis of the number of removed lymph nodes and patient characteristics in the pT1-pT4 subgroups in the Surveillance, Epidemiology, and End Results validation cohort

Characteristics	pT1 (2746), RLNs			P value	pT2 (1534), RLNs			P value	pT3 (4570), RLNs			P value	pT4 (2304), RLNs			P value
	≤ 12	13-24	≥ 25		≤ 17	18-30	≥ 31		≤ 19	20-38	≥ 39		≤ 16	17-44	≥ 45
Sex				0.521				0.263				0.033				0.668
Male	727	678	288		584	305	121		1988	1012	223		576	630	82
Female	428	439	186		316	138	70		775	469	103		448	511	57
Age (yr)				0.018				0.049				0.006				0.054
≤ 60	278	305	145		252	133	64		869	499	130		306	384	53
> 60	877	810	329		648	410	127		1894	982	196		718	757	86
Tumor location				0.008				0.001				< 0.001				< 0.001
Upper third	354	382	140		348	168	54		1391	709	93		159	143	13
Middle third	134	139	81		93	59	39		188	146	54		109	172	34
Lower third	667	596	253		459	216	98		1184	626	179		756	826	92
Tumor size (mm)				0.575				0.009				< 0.001				0.002
≤ 50	966	934	387		695	314	132		1581	749	149		443	417	46
> 50	189	183	87		205	129	59		1182	432	177		581	724	93
Histological type				0.648				0.945				0.951				0.193
Well-moderately differentiated	538	502	217		304	138	67		782	427	86		169	147	25
Poorly-undifferentiated	316	314	141		304	158	62		1212	628	144		397	469	52
Signet ring cell	187	193	64		123	58	26		406	228	51		238	288	37
Others	114	108	52		169	89	36		363	198	45		220	237	25
pN stage				< 0.001				< 0.001				< 0.001				< 0.001
pN0	1008	885	369		547	255	96		1196	526	94		253	166	16
pN1	115	148	53		216	91	39		664	275	48		236	135	19
pN2	28	63	30		106	52	31		561	311	55		298	212	21
pN3	4	21	22		31	45	25		342	369	129		237	628	83
pTNM				< 0.001				< 0.001				< 0.001				< 0.001
I	1123	1033	422		547	255	96		0	0	0		0	0	0
II	32	82	46		322	143	70		1860	801	142		180	130	13
III	0	2	6		31	45	25		903	680	184		844	1011	126

Tumor location, tumor size, pTNM stage, histological type and the number of removed lymph nodes were determined according to the postoperative pathology report. Statistically significant P values are in bold (P < 0.05).

RLNs: Retrieved lymph nodes.

Table 5 Prognostic factors of patients with gastric cancer by univariate and multivariate analyses based on Cox regression analysis in the Chinese validation cohort

Characteristics	Multivariate analysis, pT1		Multivariate analysis, pT2		Multivariate analysis, pT3		Multivariate analysis, pT4
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
Sex		-		-		-		-
Male
Female
Age	1.056 (1.030-1.082)	< 0.001	1.048 (1.024-1.072)	< 0.001	1.016 (1.007-1.025)	< 0.001	1.021 (1.013-1.029)	< 0.001
Tumor location		0.034		-		0.122		-
Upper third	1				1
Middle third	0.384 (0.151-0.972)	0.043			0.828 (0.623-1.100)	0.192
Lower third	0.413 (0.209-0.815)	0.011			0.783 (0.619-0.989)	0.040
Tumor size (mm)		-		-		< 0.001		< 0.001
≤ 50					1		1
> 50					1.435 (1.201-1.715)		1.422 (1.209-1.671)
Histological type		-		-		0.260		-
Well-moderately differentiated					1
Poorly-undifferentiated					1.133 (0.934-1.374)	0.204
Signet ring cell					1.305 (0.993-1.374)	0.056
Others					1.037 (0.993-1.716)	0.851
MLNs	1.224 (1.133-1.322)	< 0.001	1.067 (1.049-1.086)	< 0.001	1.063 (1.052-1.073)	< 0.001	1.053 (1.044-1.063)	< 0.001
RLNs	0.976 (0.954-0.999)	0.044	0.979 (0.960-0.999)	0.037	0.988 (0.979-0.996)	0.003	0.974 (0.967-0.981)	< 0.001
Chemotherapy		-		-		-		-
Yes
No/unknown

-: Univariate analysis was not statistically significant; RLNs: Retrieved lymph nodes; MLNs: Metastatic lymph nodes.

Table 6 Prognostic factors of patients with gastric cancer by univariate and multivariate analyses based on Cox regression analysis in the Surveillance, Epidemiology, and End Results validation cohort

Characteristics	Multivariate analysis, pT1		Multivariate analysis, pT2		Multivariate analysis, pT3		Multivariate analysis, pT4
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
Sex		0.001		-		-		-
Male	1
Female	0.712 (0.596-0.851)
Age	1.044 (1.035-1.052)	< 0.001	1.032 (1.024-1.040)	< 0.001	1.018 (1.014-1.022)	< 0.001	1.018 (1.014-1.022)	< 0.001
Tumor location		< 0.001		< 0.001		-		0.007
Upper third	1		1				1
Middle third	0.491 (0.364-0.661)	< 0.001	0.671 (0.496-0.908)	0.010			0.883 (0.718-1.085)	0.235
Lower third	0.636 (0.534-0.758)	< 0.001	0.603 (0.501-0.726)	< 0.001			1.122 (0.963-1.308)	0.140
Tumor size (mm)		-		0.004		< 0.001		< 0.001
≤ 50			1		1		1
> 50			1.323 (1.091-1.604)		1.172 (1.079-1.274)		1.285 (1.157-1.427)
Histological type		-		-		-		-
Well-moderately differentiated
Poorly-undifferentiated
Signet ring cell
Others
MLNs	1.111 (1.088-1.135)	< 0.001	1.022 (1.013-1.030)	< 0.001	1.024 (1.021-1.027)	< 0.001	1.035 (1.030-1.039)	< 0.001
RLNs	0.978 (0.969-0.986)	< 0.001	0.981 (0.973-0.990)	< 0.001	0.986 (0.983-0.990)	< 0.001	0.973 (0.969-0.978)	< 0.001
Chemotherapy		-		0.002		-		-
Yes			1
No/unknown			1.323 (1.110-1.577)

-: Univariate analysis was not statistically significant; RLNs: Retrieved lymph nodes; MLNs: Metastatic lymph nodes; HR: Hazard ratio; CI: Confidence interval.