Analysis of clinical efficacy of proximal gastrectomy after neoadjuvant chemotherapy combined with immunotherapy for upper gastric cancer

doi:10.3877/cma.j.issn.1674-3946.2025.06.012

Abstract

Abstract:

Objective

To compare the clinical efficacy of proximal gastrectomy (PG) for upper gastric cancer (UGC) after neoadjuvant chemotherapy alone versus neoadjuvant chemotherapy combined with immunotherapy (nICT).

Methods

A retrospective collection was conducted on 257 UGC patients who underwent neoadjuvant therapy followed by surgery from January 2017 to March 2025. They were divided into two groups based on treatment modalities: the chemotherapy-alone group (n=114, receiving neoadjuvant chemotherapy) and the combined immunotherapy group (n=143, receiving neoadjuvant chemotherapy combined with PD-1 inhibitors). Data analysis was performed using SPSS 27.0 software. Measurement data with normal distribution were expressed as (±s) and analyzed by independent samples t test; measurement data with non-normal distribution were expressed as [M(Q₁, Q₃)] and analyzed by Mann-Whitney U test; counting data were expressed as [cases (%)] and analyzed by χ² test; ranked data were analyzed by Rank Sum test. P<0.05 was considered statistically significant.

Results

There were no statistically significant differences between the two groups in terms of the number of dissected lymph nodes, tumor regression grade (TRG), vascular invasion, perineural invasion, operation time, estimated intraoperative blood loss, postoperative hospital stay, surgical complications, or the incidence of grade ≥3 complications (P>0.05). The combined immunotherapy group had higher rates of pathological complete response (pCR), major pathological response, and PG implementation; in contrast, it had lower rates of lymph node metastasis and open surgery implementation compared with the neoadjuvant chemotherapy group (P<0.05). Multivariate regression analysis showed that body mass index (BMI) >24.0 kg/m², neoadjuvant immunotherapy combined with chemotherapy regimen, and maximum tumor diameter ≤5 cm were independent influencing factors for choosing PG after neoadjuvant therapy (P<0.05).

Conclusion

For locally advanced UGC, nICT achieves better tumor primary lesion regression and regional lymph node control without increasing surgical risks.

Key words: Stomach Neoplasms, Gastrectomy, Neoadjuvant Immunotherapy Combined with Chemotherapy, Clinical Efficacy

Sijun Wang, Qiong Wang, Keyu Li, Xinpu Yuan, Shuomin Zhang, Rui Ma, Tianyu Xie, Chaojun Zhang. Analysis of clinical efficacy of proximal gastrectomy after neoadjuvant chemotherapy combined with immunotherapy for upper gastric cancer[J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2025, 19(06): 637-641.

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References 23

[1]	Japanese Gastric Cancer Association. Japanese Gastric Cancer Treatment Guidelines 2021 (6th edition) [J]. Gastric Cancer, 2023, 26(1): 1-25.
[2]	Song JH, Park SH, Cho M, et al. Proximal Gastrectomy Is Associated with Lower Incidence of Anemia and Vitamin B12 Deficiency Compared to Total Gastrectomy in Patients with Upper Gastric Cancer [J]. Cancer Res Treat, 2025, 57(1): 174-185.
[3]	Yura M, Yoshikawa T, Otsuki S, et al. Oncological safety of proximal gastrectomy for T2/T3 proximal gastric cancer [J]. Gastric Cancer, 2019, 22(5): 1029-1035.
[4]	De Jongh C, Triemstra L, Van Der Veen A, et al. Pattern of lymph node metastases in gastric cancer: a side-study of the multicenter LOGICA-trial [J]. Gastric Cancer, 2022, 25(6): 1060-1072.
[5]	Chen Y, Chen X, Lin Y, et al. Oncological risk of proximal gastrectomy for proximal advanced gastric cancer after neoadjuvant chemotherapy [J]. BMC Cancer, 2024, 24(1): 255.
[6]	Kurokawa Y, Takeuchi H, Doki Y, et al. Mapping of Lymph Node Metastasis From Esophagogastric Junction Tumors: A Prospective Nationwide Multicenter Study [J]. Ann Surg, 2021, 274(1): 120-127.
[7]	Yuan Z, Cui H, Xu Q, et al. Total versus proximal gastrectomy for proximal gastric cancer after neoadjuvant chemotherapy: a multicenter retrospective propensity score-matched cohort study [J]. Int J Surg, 2024, 110(2): 1000-1007.
[8]	Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial [J]. Lancet, 2021, 398(10294): 27-40.
[9]	Shitara K, Rha SY, Wyrwicz LS, et al. Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585): an interim analysis of the multicentre, double-blind, randomised phase 3 study[J]. Lancet Oncol, 2024, 25(2): 212-214.
[10]	Yuan SQ, Nie RC, Jin Y, et al. Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial[J]. Nat Med, 2024, 30(2): 552-559.
[11]	Zhang X, Liang H, Li Z, et al. Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial [J]. Lancet Oncol, 2021, 22(8): 1081-1092.
[12]	李子禹, 贾永宁, 卢信星, 等. 免疫治疗时代下的胃癌外科[J]. 中华外科杂志, 2024, 62(05): 353-358.
[13]	中国临床肿瘤学会（CSCO）. 胃癌诊疗指南2025[M]. 北京: 人民卫生出版社, 2025.
[14]	Clavien PA, Barkun J, De Oliveira ML, et al. The Clavien-Dindo classification of surgical complications: five-year experience[J]. Ann Surg, 2009, 250(2): 187-196.
[15]	Network NCC. NCCN Clinical Practice Guidelines in Oncology: Gastric Cancer [J]. 2025.
[16]	Mine S, Kurokawa Y, Takeuchi H, et al. Distribution of involved abdominal lymph nodes is correlated with the distance from the esophagogastric junction to the distal end of the tumor in Siewert type Ⅱ tumors [J]. Eur J Surg Oncol, 2015, 41(10): 1348-1353.
[17]	Su PJ, Huang YT, Liao TK, et al. Comparing survival after proximal gastrectomy vs. total gastrectomy in advanced gastric cancer: A systematic review and meta-analysis [J]. Oncol Lett, 2024, 28(3): 427.
[18]	Li S, Yu W, Xie F, et al. Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer [J]. Nat Commun, 2023, 14(1): 8.
[19]	Janjigian YY, Al-Batran SE, Wainberg ZA, et al. Perioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer [J]. N Engl J Med, 2025, 393(3): 217-230.
[20]	Janjigian YY, Al-Batran SE, Wainberg ZA, et al. Event-free survival (EFS) in MATTERHORN: A randomized, phase 3 study of durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel chemotherapy (FLOT) in resectable gastric/gastroesophageal junction cancer (GC/GEJC) [J]. J Clin Oncol, 2025, 43(17_suppl): LBA5-LBA6.
[21]	陈新华, 林和新, 陈粤泓, 等. 术前使用免疫检查点抑制剂对胃癌转移淋巴结癌残留影响的回顾性研究 [J]. 中华胃肠外科杂志, 2024, 27(07): 694-701.
[22]	Sun YQ, Zhong Q, Lv CB, et al. The safety and efficacy of neoadjuvant immunochemotherapy following laparoscopic gastrectomy for gastric cancer: a multicentre real-world clinical study [J]. Int J Surg, 2024, 110(8): 4830-4838.
[23]	Rahim MK, Okholm TLH, Jones KB, et al. Dynamic CD8(+) T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes [J]. Cell, 2023, 186(6): 1127-1143. e18.

组别	例数	性别（例）	年龄（岁，±s）	BMI（kg/m²，±s）	NRS2002（例）
组别	例数	男/女	年龄（岁，±s）	BMI（kg/m²，±s）	有风险/无风险
单纯化疗组	114	98/16	62.8±8.9	23.3±3.4	21/93
联合免疫组	143	115/28	63.5±8.3	24.0±3.5	41/102
t/χ²/Z值		1.375	-0.709	-1.631	3.641
P值		0.241	0.479	0.104	0.056
组别	例数	ASA分级标准（例）	aCCI评分（例）	cT分期（例）	cN分期（例）
组别	例数	Ⅰ/Ⅱ/Ⅲ/Ⅳ	<4/≥4	cT₂/cT₃/cT₄	cN₀/cN₊
单纯化疗组	114	3/99/11/1	105/9	1/37/76	6/108
联合免疫组	143	1/125/17/0	125/18	1/54/88	13/130
t/χ²/Z值		0.484	1.486	-0.829	0.983
P值		0.484	0.223	0.407	0.321
组别	例数	新辅助治疗周期（例）	肿瘤浸润（例）	含有印戒细胞癌（例）	含有黏液腺癌（例）
组别	例数	<4个/≥4个	A/B	是/否	是/否
单纯化疗组	114	43/71	69/45	28/86	8/106
联合免疫组	143	41/102	90/53	23/120	5/138
t/χ²/Z值		2.360	0.156	2.866	1.638
P值		0.124	0.693	0.090	0.201

组别	例数	性别（例）	年龄（岁，±s）	BMI（kg/m²，±s）	NRS2002（例）
组别	例数	男/女	年龄（岁，±s）	BMI（kg/m²，±s）	有风险/无风险
单纯化疗组	114	98/16	62.8±8.9	23.3±3.4	21/93
联合免疫组	143	115/28	63.5±8.3	24.0±3.5	41/102
t/χ²/Z值		1.375	-0.709	-1.631	3.641
P值		0.241	0.479	0.104	0.056
组别	例数	ASA分级标准（例）	aCCI评分（例）	cT分期（例）	cN分期（例）
组别	例数	Ⅰ/Ⅱ/Ⅲ/Ⅳ	<4/≥4	cT₂/cT₃/cT₄	cN₀/cN₊
单纯化疗组	114	3/99/11/1	105/9	1/37/76	6/108
联合免疫组	143	1/125/17/0	125/18	1/54/88	13/130
t/χ²/Z值		0.484	1.486	-0.829	0.983
P值		0.484	0.223	0.407	0.321
组别	例数	新辅助治疗周期（例）	肿瘤浸润（例）	含有印戒细胞癌（例）	含有黏液腺癌（例）
组别	例数	<4个/≥4个	A/B	是/否	是/否
单纯化疗组	114	43/71	69/45	28/86	8/106
联合免疫组	143	41/102	90/53	23/120	5/138
t/χ²/Z值		2.360	0.156	2.866	1.638
P值		0.124	0.693	0.090	0.201

组别	例数	淋巴结清扫数目（枚，±s）	TRG（例）	脉管浸润（例）	神经侵犯（例）
组别	例数	淋巴结清扫数目（枚，±s）	0/1/2/3	是/否	是/否
单纯化疗组	114	28.4±12.9	9/24/65/16	35/79	34/80
联合免疫组	143	28.6±12.4	29/33/56/25	33/110	44/99
t/χ²/Z值		-0.101	0.069	1.895	0.027
P值		0.920	0.069	0.169	0.870
组别	例数	pCR [例（%）]	主要病理缓解[例（%）]	转移淋巴结数目[枚，M(Q₁, Q₃)]
组别	例数	是/否	是/否	转移淋巴结数目[枚，M(Q₁, Q₃)]
单纯化疗组	114	8（7.0）/106（93.0）	33（28.9）/81（71.1）	1.0 (0.0，5.0)
联合免疫组	143	24（16.8）/119（83.2）	62（43.4）/81（56.6）	0.0 (0.0，3.0)
t/χ²/Z值		5.549	5.652	-3.163
P值		0.018	0.017	0.002
组别	例数	ypT分期[例（%）]	ypN分期[例（%）]	ypTNM分期[例（%）]
组别	例数	T₀/T₁/T₂/T₃/T_4a/T_4b	N₀/N₁/N₂/N_3a/N_3b	0/I/Ⅱ/Ⅲ
单纯化疗组	114	8/7/19/70/10/0	45/25/17/19/8	8/15/53/38
联合免疫组	143	29/20/18/62/13/1	83/24/19/12/5	25/33/44/41
t/χ²/Z值		-2.838	-3.095	-2.599
P值		0.005	0.002	0.009

组别	例数	淋巴结清扫数目（枚，±s）	TRG（例）	脉管浸润（例）	神经侵犯（例）
组别	例数	淋巴结清扫数目（枚，±s）	0/1/2/3	是/否	是/否
单纯化疗组	114	28.4±12.9	9/24/65/16	35/79	34/80
联合免疫组	143	28.6±12.4	29/33/56/25	33/110	44/99
t/χ²/Z值		-0.101	0.069	1.895	0.027
P值		0.920	0.069	0.169	0.870
组别	例数	pCR [例（%）]	主要病理缓解[例（%）]	转移淋巴结数目[枚，M(Q₁, Q₃)]
组别	例数	是/否	是/否	转移淋巴结数目[枚，M(Q₁, Q₃)]
单纯化疗组	114	8（7.0）/106（93.0）	33（28.9）/81（71.1）	1.0 (0.0，5.0)
联合免疫组	143	24（16.8）/119（83.2）	62（43.4）/81（56.6）	0.0 (0.0，3.0)
t/χ²/Z值		5.549	5.652	-3.163
P值		0.018	0.017	0.002
组别	例数	ypT分期[例（%）]	ypN分期[例（%）]	ypTNM分期[例（%）]
组别	例数	T₀/T₁/T₂/T₃/T_4a/T_4b	N₀/N₁/N₂/N_3a/N_3b	0/I/Ⅱ/Ⅲ
单纯化疗组	114	8/7/19/70/10/0	45/25/17/19/8	8/15/53/38
联合免疫组	143	29/20/18/62/13/1	83/24/19/12/5	25/33/44/41
t/χ²/Z值		-2.838	-3.095	-2.599
P值		0.005	0.002	0.009

组别	例数	手术方式[例（%）]	手术入路[例（%）]	手术时间（min，±s）
组别	例数	PG/TG	腹腔镜/机器人/开腹	手术时间（min，±s）
单纯化疗组	114	39(34.2)/75(65.8)	88(77.2)/12(10.5)/14(12.3)	229.9±74.2
联合免疫组	143	74(51.7)/69(48.3)	124(86.7)/17(11.9)/2(1.4)	238.0±69.5
t/χ²/Z值		7.919	12.867	-0.906
P值		0.005	0.002	0.366
组别	例数	术中出血量[ml，M(Q₁，Q₃)]	术后住院时间[d，M(Q₁，Q₃)]	手术并发症[例（%）]	≥3级并发症[例（%）]
组别	例数	术中出血量[ml，M(Q₁，Q₃)]	术后住院时间[d，M(Q₁，Q₃)]	有/无	有/无
单纯化疗组	114	100(50.0，200.0)	8.0(7.0，10.0)	13(11.4)/101(88.6)	8(7.0)/106(93.0)
联合免疫组	143	100(50.0，150.0)	8.0(7.0，10.0)	26(18.2)/117(81.8)	15(10.5)/128(89.5)
t/χ²/Z值		-1.244	-0.290	2.264	0.938
P值		0.214	0.772	0.132	0.333

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