Prognostic value of modified Lauren classification in gastric cancer

Table 1 Basic characteristics according to anatomical location using the modified Lauren classification

Variable	Distal non-diffuse type	Proximal non-diffuse type	Diffuse type
Gender (%)
Male	416 (63.6)	324 (70.0)	848 (53.0)
Female	238 (36.4)	139 (30.0)	753 (47.0)
Age (%)
< 60 yr	200 (30.6)	167 (36.1)	850 (53.1)
≥ 60 yr	454 (69.4)	296 (63.9)	751 (46.9)
Tumor size (%)
< 4.0 cm	318 (48.6)	218 (47.1)	664 (41.5)
≥ 4.0 cm	310 (47.4)	221 (47.7)	771 (48.2)
Unknown	26 (4.0)	24 (5.2)	166 (10.4)
Retrieved lymph nodes (%)
Adequate (n ≥ 16)	326 (49.8)	261 (56.4)	831 (51.9)
Inadequate (n < 16)	328 (50.2)	202 (43.6)	770 (48.1)
AJCC 8th pT stage (%)
pT1	211 (32.3)	123 (26.6)	356 (22.2)
pT2	87 (13.3)	69 (14.9)	173 (10.8)
pT3	207 (31.7)	149 (32.2)	464 (29.0)
pT4a	101 (15.4)	89 (19.2)	480 (30.0)
pT4b	48 (7.3)	33 (7.1)	128 (8.0)
AJCC 8th pN stage (%)
pN0	302 (46.2)	197 (42.5)	532 (33.2)
pN1	117 (17.9)	79 (17.1)	260 (16.2)
pN2	115 (17.6)	90 (19.4)	302 (18.9)
pN3a	95 (14.5)	70 (15.1)	347 (21.7)
pN3b	25 (3.8)	27 (5.8)	160 (10.0)
Differentiation grade (%)
Well differentiation	66 (10.1)	26 (5.6)	3 (0.2)
Moderate differentiation	269 (41.1)	170 (36.7)	44 (2.7)
Poor differentiation	311 (47.6)	259 (55.9)	1484 (92.7)
Undifferentiation	8 (1.2)	8 (1.7)	70 (4.4)

AJCC: American Joint Committee on Cancer; pN stage: Pathological N stage; pT stage: Pathological T stage.

Table 2 Univariate and multivariable analyses of prognostic factors for overall survival

Variable	No. of patients (%)	Univariate analysis		Multivariate analysis
		5-yr OS	P value	HR (95%CI)	P value
Gender (%)			0.111
Male	1588 (58.4)	45.9%
Female	1130 (41.6)	49.1%
Age (%)			< 0.001		< 0.001
< 60 yr	1217 (44.8)	50.7%		1 (Ref)	–
≥ 60 yr	1501 (55.2)	44.4%		1.157 (1.360–1.692)	< 0.001
Tumor size (%)			< 0.001		0.001
≤ 4.0 cm	1200 (44.2)	63.9%		1 (Ref)	–
> 4.0 cm	1302 (47.9)	33.6%		1.179 (1.038–1.339)	0.011
Unknown	216 (7.9)	40.2%		1.457 (1.191–1.782)	< 0.001
Retrieved lymph nodes (%)			0.074		< 0.001
Adequate (n ≥ 16)	1418 (52.2)	48.9%		1 (Ref)	–
Inadequate (n < 16)	1300 (47.8)	45.5%		1.550 (1.380–1.740)	< 0.001
AJCC 8th pT stage (%)			< 0.001		< 0.001
pT1	690 (25.4)	80.9%		1 (Ref)	–
pT2	329 (12.1)	66.6%		1.535 (1.193–1.975)	0.001
pT3	820 (30.2)	38.5%		2.882 (2.334–3.558)	< 0.001
pT4a	670 (24.7)	23.4%		3.415 (2.740–4.256)	< 0.001
pT4b	209 (7.7)	18.6%		4.452 (3.458–5.732)	< 0.001
AJCC 8th pN stage (%)			< 0.001		< 0.001
pN0	1031 (37.9)	71.6%		1 (Ref)	–
pN1	456 (16.8)	46.9%		1.467 (1.225–1.757)	< 0.001
pN2	507 (18.7)	37.5%		1.611 (1.353–1.919)	< 0.001
pN3a	512 (18.8)	24.8%		2.356 (1.976–2.809)	< 0.001
pN3b	212 (7.8)	9.2%		4.138 (3.306–5.181)	< 0.001
Differentiation grade (%)			0.011		0.135
Well differentiation	95 (3.5)	69.4%		1 (Ref)	–
Moderate differentiation	483 (17.8)	58.9%		0.974 (0.649–1.462)	0.898
Poor differentiation	2054 (75.5)	44.0%		1.123 (0.755–1.670)	0.566
Undifferentiation	86 (3.2)	35.6%		1.415 (0.876–2.285)	0.156
Modified Lauren classification (%)			< 0.001		0.013
Distal non-diffuse type	654 (24.1)	58.8%		1 (Ref)	–
Proximal non-diffuse type	463 (17.0)	48.3%		1.230 (1.033–1.466)	0.020
Diffuse type	1601 (58.9)	42.4%		1.246 (1.068–1.452)	0.005

AJCC: American Joint Committee on Cancer; HR: Hazard ratio; OS: Overall survival; pN stage: Pathological N stage; pT stage: Pathological T stage. Variables with P values less than 0.1 were included in the multivariate analysis.

Table 3 Comparison of predictive performances between different pathological classifications and prognostic models

Pathological classification/prognostic model	AUC (95%CI)		AIC
	3-yr overall survival	5-yr overall survival
Differentiation grade	0.626 (0.608–0.644)	0.621 (0.602–0.639)	25971
Lauren classification	0.666 (0.647–0.683)	0.681 (0.663–0.699)	25923
Modified Lauren classification	0.679 (0.661–0.696)	0.702 (0.685–0.719)	25877
DeLong tests for AUCs
Differentiation grade vs Lauren	P < 0.001	P < 0.001	–
Lauren vs modified Lauren	P < 0.001	P < 0.001	–
Modified Lauren vs differentiation grade	P < 0.001	P < 0.001	–
Novel prognostic model	0.803 (0.786–0.819)	0.804 (0.787–0.820)	20010
Age, tumor size, retrieved lymph nodes, pT stage, pN stage, modified Lauren classification
Control model	0.776 (0.759–0.793)	0.776 (0.759–0.793)	20144
AJCC 8th pTNM stage (pT stage, pN stage)

AIC: Akaike's Information Criterion; AJCC: American Joint Committee on Cancer; AUC: Area under curve; pN stage: Pathological N stage; pT stage: Pathological T stage. A higher area under the curve indicated better model discrimination and a lower Akaike's Information Criterion indicates superior model-fitting; Differentiation grade, well vs moderate vs poor vs undifferentiation; Lauren classification, intestinal type vs diffuse type vs mixed type; Modified Lauren classification, distal non-diffuse vs proximal non-diffuse vs diffuse type.