Timing of surgery after neoadjuvant chemotherapy for gastric cancer: Impact on outcomes

Table 1 Demographic and tumor characteristics according to the neoadjuvant chemotherapy-surgery interval time and pathological complete response status n (%)

	< 4 wk (n = 111)	4-6 wk (n = 48)	> 6 wk (n = 17)	P value	pCR (n = 40)	No pCR (n = 136)	P value
Age, yr, mean ± SD	55.5585 ± 10.8079	59.7916 ± 9.7891	61.5882 ± 9.5985	0.014	57.375 ± 9.862354	57.27206 ± 10.88013	0.908
Sex				0.974			0.174
Male	87 (78.38)	37 (77.08)	13 (76.47)		28 (70.00)	109 (80.15)
Female	24 (21.62)	11 (22.92)	4 (23.53)		12 (3.00)	27 (19.85)
Chemotherapy cycles				0.692			1.000
< 4	39 (35.14)	17 (35.42)	4 (23.53)		14 (35.00)	46 (33.82)
≥ 4	72 (64.86)	31 (64.58)	13 (76.47)		26 (65.00)	90 (66.18)
ASA, yr, mean ± SD				0.083			0.467
1	8 (7.21)	1 (2.8)	2 (11.76)		4 (10.00)	7 (5.15)
2	97 (87.39)	39 (81.25)	15 (88.24)		32 (80.00)	119 (87.50)
3	6 (5.40)	8 (16.67)	0		4 (10.00)	10 (7.35)
Histology (before NACT)				0.398			0.658
Tubular adenocarcinoma	90 (81.08)	40 (83.33)	15 (88.24)		34 (85.00)	111 (81.62)
Mucinous	10 (9.01)	1 (2.08)	0 (0.00)		1 (2.50)	10 (7.35)
Signet ring cell	9 (9.11)	4 (8.33)	1 (5.88)		3 (7.50)	11 (8.09)
mixed type1	2 (1.80)	3 (6.25)	1 (5.88)		2 (5.00)	4 (2.94)
Differentiation (before NACT)				0.000			0.032
Well	2 (1.80)	0 (0.00)	15 (88.24)		2 (5.00)	0 (0.00)
Moderate	28 (25.23)	10 (20.83)	1 (5.88)		10 (25.00)	35 (25.74)
Poor	81 (72.97)	38 (79.17)	1 (5.88)		28 (79.00)	101 (74.26)
Clinical T stage				0.006			0.027
2	31 (27.93)	17 (35.42)	6 (35.29)		15 (37.50)	39 (28.68)
3	24 (21.62)	19 (39.58)	8 (47.06)		16 (40.00)	35 (19.85)
4	56 (50.45)	12 (25.00)	3 (17.65)		9 (22.50)	62 (51.47)
Clinical N stage				0.170			0.012
Positive	89 (80.18)	33 (68.75)	11 (64.71)		24 (60.00)	109 (88.97)
Negative	22 (19.82)	15 (31.25)	6 (35.29)		16 (40.00)	27 (11.03)
Tumor location				0.650			0.044
Upper	45 (40.54)	23 (47.92)	6 (35.29)		10 (25.00)	64 (47.06)
Middle	16 (14.41)	7 (14.58)	2 (11.76)		6 (15.00)	19 (13.97)
Lower	45 (40.54)	14 (29.17)	7 (41.18)		22 (55.00)	44 (32.35)
Diffuse type2	5 (4.51)	4 (8.33)	2 (11.76)		2 (5.00)	9 (6.62)
Tumor diameter (before NACT)				0.134			0.069
≤ 2 cm	15 (13.51)	8 (16.67)	2 (11.76)		7 (17.50)	18 (2.21)
2-5 cm	50 (45.05)	21 (43.75)	13 (76.47)		24 (60.00)	60 (69.85)
≥ 5 cm	46 (41.44)	19 (39.58)	2 (11.76)		9 (12.50)	58 (27.94)
Surgical procedure				0.363			0.002
Proximal gastrectomy	21 (18.92)	10 (20.83)	2 (11.76)		9 (22.50)	24 (17.65)
Distal gastrectomy	32 (28.83)	10 (20.83)	8 (47.06)		19 (47.50)	31 (22.79)
Total gastrectomy	58 (52.25)	28 (58.33)	7 (41.18)		12 (30.00)	81 (59.56)
NACT-surgery interval time							0.043
< 4 wk					27 (67.50)	84 (61.76)
4-6 wk					6 (15.00)	42 (30.88)
> 6 wk					7 (17.50)	10 (7.35)
ypT stage				0.045
0	27 (24.32)	6 (12.50)	7 (41.18)
1	7 (6.31)	9 (18.75)	3 (17.65)
2	25 (22.52)	6 (12.50)	2 (11.76)
3	38 (34.23)	15 (31.25)	4 (23.53)
4	14 (12.61)	12 (25.00)	1 (5.88)
ypN stage				0.187
0	67 (60.30)	23 (47.92)	14 (82.35)
1	7 (6.31)	7 (14.58)	2 (11.76)
2	16 (14.41)	5 (10.42)	1 (5.88)
3a	14 (12.61)	8 (16.67)	0
3b	7 (6.31)	5 (10.42)	0

¹Mixed type: the tumor contains at least two kinds of cancer cell with different pathological classification, and the proportion of cancer cells in each type is similar;

²Diffuse type: the region of tumor is beyond one part of the stomach (three parts of the stomach: cardiac and gastric fundus, gastric body, and pylorus and gastric antrum). pCR: Pathological complete response; NACT: Neoadjuvant chemotherapy.

Table 2 Multivariate logistic analysis identifying independent predictors of pathological complete response

Factor	OR	95%CI	P value
Sex
Male vs female	1.76	0.74-4.18	0.201
NACT-Surgery interval time
< 4 wk vs > 6 wk	0.69	0.22-2.13	0.521
4-6 wk vs > 6 wk	0.26	0.07-0.96	0.044
Clinical T stage
T2 vs T4	1.99	0.70-5.68	0.200
T3 vs T4	2.90	1.04-8.01	0.041
Clinical N stage
Positive vs negative	2.12	0.90-4.97	0.086
Tumor diameter (before NACT)
≤ 2 cm vs ≥ 5 cm	1.60	0.44-5.80	0.472
2-5 cm vs ≥ 5 cm	1.58	0.60-4.14	0.354

NACT: Neoadjuvant chemotherapy.

Table 3 Multivariable analysis identifying independent predictors of overall survival and disease-free survival

Independent predictor	3-yr estimate (overall survival)			3-yr estimate (disease-free survival)
	HR	95%CI	P value	HR	95%CI	P value
NACT-Surgery interval time
< 4 wk vs > 6 wk	0.49	0.11-2.129	0.340	0.43	0.10-1.85	0.258
4-6 wk vs > 6 wk	0.99	0.24-4.06	0.985	0.93	0.23-3.80	0.922
Age
≤ 60 vs > 60	0.90	0.34-2.37	0.833	0.84	0.32-2.19	0.720
Sex
Female vs male	1.27	0.40-4.04	0.688	1.24	0.39-3.99	0.716
Histology (before NACT)
Tubular adenocarcinoma vs mixed type	2.56	0.24-26.94	0.433	2.25	0.22-22.56	0.491
Mucinous vs mixed type	3.79	0.21-70.55	0.372	3.12	0.18-53.99	0.435
Signet ring cell vs mixed type	5.71	0.40-81.22	0.199	4.99	0.37-66.54	0.224
Differentiation (before NACT)
Well and moderate vs poor	2.49	0.99-6.24	0.052	2.45	0.98-6.11	0.054
Clinical T stage
T2 vs T4	1.51	0.42-5.39	0.524	1.67	0.48-5.84	0.422
T3 vs T4	0.99	0.31-3.16	0.980	0.98	0.31-3.11	0.968
Clinical N stage
Positive vs negative	0.45	0.13-1.62	0.221	0.49	0.14-1.74	0.270
Tumor diameter (before NACT)
≤ 2 cm vs ≥ 5 cm	3.16	0.61-16.45	0.171	2.88	0.57-14.65	0.202
2-5 cm vs ≥ 5 cm	1.91	0.72-5.10	0.196	1.74	0.65-4.65	0.267
Tumor location
Upper vs diffuse type	1.04	0.15-7.33	0.973	0.99	0.14-6.98	0.989
Middle vs diffuse type	1.11	0.16-7.78	0.915	1.16	0.17-8.05	0.879
Lower vs diffuse type	4.41	0.78-25.18	0.095	3.94	0.69-22.50	0.123
Surgical procedure
Proximal gastrectomy vs total gastrectomy	0.69	0.17-2.73	0.593	0.79	0.20-3.07	0.729
Distal gastrectomy vs total gastrectomy	0.12	0.33-0.42	0.001	0.13	0.36-0.44	0.001
ypT stage
T0 vs T4	1.04	0.15-7.20	0.968	1.27	0.18-9.08	0.811
T1 vs T4	0.57	0.09-4.14	0.601	0.588	0.86-4.04	0.589
T2 vs T4	1.15	0.24-5.53	0.858	1.29	0.26-6.46	0.756
T3 vs T4	0.60	0.15-2.09	0.387	0.59	0.16-2.18	0.425
ypN stage
N0 vs N3	0.16	0.37-0.70	0.015	0.11	024-0.52	0.005
N1 vs N3	0.14	0.02-0.81	0.029	0.17	0.02-0.71	0.020
N2 vs N3	0.47	0.11-1.98	0.302	0.40	0.09-1.67	0.208

NACT: Neoadjuvant chemotherapy.