Comparison between upfront surgery and neoadjuvant chemotherapy in patients with locally advanced gastric cancer: A systematic review

Table 1 Inclusion and exclusion criteria

Inclusion criteria	Exclusion criteria
Studies published over the last 10 yr	Studies with less than 10 patients
Studies in English language	Pilot studies and case reports
Adult patients	Patients with metastatic disease
Patients with locally advanced gastric cancer

Table 2 Patient demographics and clinical characteristics

Ref.	Study population	Sex	Age (yr)	EGJ involvement	Staging
Ahn et al[8], 2014	140	101 males, 39 females	NAT, 53.8; US, 58.9	NS	T0, n = 2
					T1, n = 35
					T2, n = 40
					T3, n = 31
					T4, n = 28
					Unknown, n = 4
Biondi et al[9], 2018	417	262 males, 155 females	NAT, 58 ± 10; US, 55 ± 13	n = 26	0, n = 1
					I, n = 101
					II, n = 87
					III, n = 169
					IV, n = 59
Bracale et al[10], 2021	194	119 males, 75 females	NAT, 69.4; US, 70.5	None	II, n = 48
					III, n = 146
Eom et al[11], 2018	129	90 males, 39 females	NAT, 53; US, 57	None	IIIA, n = 61
					IIIB, n = 57
					IV, n = 11
Feng et al[12], 2015	170	134 males, 36 females	60 (21-82)	NS	T1, n = 5
					T2, n = 17
					T3, n = 29
					T4, n = 119
Wang et al[13], 2021	60	32 males, 28 females	32-70	NS	T3, n = 32
					T4a, n = 28
Xue et al[14], 2018	100	76 males, 24 females	69 patients < 65 yr	NS	T2, n = 10
					T3, n = 31
					T4a, n = 58
					T4b, n = 1
Kang et al[15], 2021	484	384 males, 100 females	58 (20-75)	NS	T2, n = 25
					T3, n = 116
					T4a, n = 305
					T4b, n = 38
Kano et al[16], 2019	76	61 males, 15 females	NAT, 69.3 ± 7.76; US, 70.4 ± 8.5	None	IIB, n = 27
					IIIA-C, n = 49
Lin et al[17], 2022	462	349 males, 113 females	NAT, 58; AT, 61	NS	T0, n = 10
					T1, n = 18
					T2, n = 65
					T3, n = 101
					T4, n = 158
Marino et al[18], 2021	177	107 males, 70 females	73.3 ± 10.4	NS	T2, n = 4
					T3, n = 27
					T4, n = 16
Molina et al[19], 2013	40 (39 surgery)	29 males, 11 females	64.3 (39.1-82.2)	NS	II, n = 21
					III, n = 19
Pardo et al[20], 2020	814	513 males, 295 females	351 patients < 70; 399 patients > 70	NS	T1, n = 6
					T2, n = 210
					T3, n = 375
					T4a, n = 164
					T4b, n = 31
Wang et al[21], 2019	82	65 males, 17 females	NAT, 23 patients < 60, 18 patients > 60; US, 24 patients < 60, 17 patients > 60	None	II, n = 22
					III, n = 60
Wang et al[22], 2021	778	580 males, 198 females	NAT, 56.13; US, 55.94	None	II, n = 132
					III, n = 646
Wu et al[23], 2019	172	139 males, 33 females	NAT, 54.83; US, 54.98	NS	II, n = 10
					III, n = 162
Xu et al[24], 2021	442	331 males, 114 females	NAT, 63; US, 61	NS	T4, n = 442
Zhao et al[25], 2017	102	82 males, 20 females	59 (34-77)	NS	IIB, n = 23
					IIIA, n = 39
					IIIB/C, n = 40

EGJ: Esophagogastric Junction; NAT: Neoadjuvant chemotherapy; US: Upfront surgery; NS: Not stated.

Table 3 Overall survival and disease-free survival of patients after neoadjuvant chemotherapy and surgery versus upfront surgery

Ref.	Overall survival		P value	Disease-free survival		P value
	NAT	US		NAT	US
Ahn et al[8], 2014	NS	NS		NS	NS
Biondi et al[9], 2018	> 60 mo	45 mo	0.519	NS	NS
Bracale et al[10], 2021	72%	71%	0.41	71%	75%	0.34
Eom et al[11], 2018	73.3%	51.1%	0.005	62.8%	49.9%	0.145
Feng et al[12], 2015	NS	NS		NS	NS
Wang et al[13], 2021	63.3%	50%	0.215	60%	33.3%	0.019
Xue et al[14], 2018	70%	74%	> 0.05	NS	NS
Kang et al[15], 2021	74.2%	73.4%	> 0.05	66.3%	60.2%	0.023
Kano et al[16], 2019	NS	NS		80%	58.7%	0.037
Lin et al[17], 20221	Eastern: 60.1%. Western: 57.3%	Eastern: 49.3%. Western: 39.5%	Eastern: 0.02. Western: 0.11	NS	NS
Marino et al[18], 2021	50 mo	35 mo	> 0.05	48 mo		> 0.05
Molina et al[19], 2013		39.01%			34.05%
Pardo et al[20], 2020	41.6%	38.6%	0.089	NS	NS
Wang et al[21], 2019	58.7%	30.9%	0.008	NS	NS
Wang et al[22], 2021	52 mo	26.4 mo	< 0.001	NS2	NS2
Wu et al[23], 2019	NS	NS		NS	NS
Xu et al[24], 2021	72.29%	36.22%	< 0.001	58.53%	30.87%	< 0.001
Zhao et al[25], 2017	17.9 mo	17.4 mo	> 0.05	16.1 mo	15.8 mo	> 0.05

¹All patients received neoadjuvant chemotherapy; adjuvant chemotherapy (first column) and non-adjuvant chemotherapy groups (second column) were compared in two independent (an eastern and a western) cohorts.

²Not stated for neoadjuvant chemotherapy vs upfront surgery. But nCRT (chemoradio-) significantly better than nCT (chemo-) (P = 0.014).

NAT: Neoadjuvant chemotherapy; US: Upfront surgery; NS: Not stated.

Table 4 Morbidity and mortality of patients after neoadjuvant chemotherapy and surgery versus upfront surgery

Ref.	Morbidity		P value	Mortality		P value
	NAT	US		NAT	US
Ahn et al[8], 2014	22.9%	29.3%		0	2.1%
Biondi et al[9], 2018	21.4%	12.9%	0.178	0	3.7%
Bracale et al[10], 2021	38.1%	21.6%	0.019	0	2.1%
Eom et al[11], 2018	14.3%	15.1%	0.999	0	0
Feng et al[12], 2015	18.8%	22.2%	0.704	NS	NS
Wang et al[13], 2021	23.1%	30%	0.56	NS	NS
Xue et al[14], 2018	30%	28%	0.986	2%	2%
Kang et al[15], 2021	8.1%	5.5%	0.175	0.4%
Kano et al[16], 2019	23.1%	40.5%	0.101	NS	NS
Lin et al[17], 2022	NS	NS		NS	NS
Marino et al[18], 2021	Less than US		> 0.05	NS	NS
Molina et al[19], 2013	-	5%		-	2.5%
Pardo et al[20], 2020	11.5%	9.9%	0.268	2.8%	5.3%	0.142
Wang et al[21], 2019	9%	17%	0.519	0	0
Wang et al[22], 2021	6.4%	0		0.2%	0
Wu et al[23], 2019	10.5%	15.1%	0.361	0	0
Xu et al[24], 2021	6.79%	12.67%	0.037	n = 172 in total
Zhao et al[25], 2017	14%	15.4%	0.844	0	0

NAT: Neoadjuvant chemotherapy; US: Upfront surgery; NS: Not stated.

Table 5 R0 resection rate of gastric cancer in patients after neoadjuvant chemotherapy and surgery versus upfront surgery

Ref.	R0 resection rate		P value
	NAT	US
Ahn et al[8], 2014	92.2%
Biondi et al[9], 2018	82.9%	83.6%	0.449
Bracale et al[10], 2021	NS	NS
Eom et al[11], 2018	97.7%	97.7%
Feng et al[12], 2015	95%	94.4%
Wang et al[13], 2021	84.6%	56.7%	0.029
Xue et al[14], 2018	100%	96%
Kang et al[15], 2021	NS	NS
Kano et al[16], 2019	100%	100%
Lin et al[17], 2022	90.1%
Marino et al[18], 2021	NS	NS
Molina et al[19], 2013	-	80%
Pardo et al[20], 2020	NS	NS
Wang et al[21], 2019	89.2%	84.6%	> 0.05
Wang et al[22], 2021	96%1	89%1	0.061
Wu et al[23], 2019	NS	NS
Xu et al[24], 2021	94.12%	89.14%	0.072
Zhao et al[25], 2017	NS	NS

¹Neoadjuvant chemoratdiotherapy versus neoadjuvant chemotherapy (96% vs 89%, P = 0.06).

NAT: Neoadjuvant chemotherapy; US: Upfront surgery; NS: Not stated.