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Cheng ZW, Wei M, Zhang Y, Liang YZ, Cao WB, Zhao RD, Yan ZB, Sun GR, Cui XH, Yu WB. Surgical safety and efficacy of neoadjuvant immunotherapy plus apatinib and chemotherapy in locally advanced gastric cancer. World J Gastroenterol 2027; 33(2): 122397 [DOI: 10.3748/wjg.122397]
Ze-Wei Cheng, Meng Wei, Yi-Ze Liang, Wei-Bo Cao, Ru-Dong Zhao, Zhi-Bo Yan, Guo-Rui Sun, Xiao-Han Cui, Wen-Bin Yu, Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
Yuan Zhang, Clinical Research Center, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
Author contributions: Cheng ZW and Yu WB participated in the conception and design of the study and were involved in the acquisition, analysis, or interpretation of data; Cheng ZW wrote the original draft and managed the project administration; Yu WB and Zhang Y accessed and verified the study data; Zhang Y performed the formal analysis, data curation, statistical analysis, and validation; Wei M, Liang YZ, Cao WB, Zhao RD, Yan ZB, Sun GR, and Cui XH were involved in the investigation, resources, data collection, and writing - review & editing. All authors critically reviewed and provided final approval of the manuscript, and were responsible for the decision to submit the manuscript for publication.
Supported by Horizontal Project of Shandong University, No. 6010123193, No. 6010121066, and No. 6010125120.
Institutional review board statement: This investigation was approved by the Institutional Ethics Committee of Qilu Hospital of Shandong University, No. KYLL-202111-094-1.
Informed consent statement: All involved persons (subjects or legally authorized representative) gave their informed consent prior to study inclusion.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Corresponding author: Wen-Bin Yu, MD, PhD, Professor, Department of General Surgery, Qilu Hospital of Shandong University, No. 107 Wenhua Xi Road, Jinan 250012, Shandong Province, China. wenbin_yu2003@163.com
Received: April 17, 2026 Revised: May 10, 2026 Accepted: June 10, 2026 Published online: January 14, 2027 Processing time: 205 Days and 22.7 Hours
Abstract
BACKGROUND
Neoadjuvant chemotherapy remains the standard for locally advanced gastric cancer (LAGC), yet outcomes remain suboptimal. Programmed cell death protein-1 inhibitors and apatinib have been used individually with chemotherapy for the treatment of LAGC, but the clinical benefit of programmed cell death protein-1 inhibitors plus apatinib and chemotherapy (PAC) as a neoadjuvant strategy requires comprehensive evaluation.
AIM
To evaluate the surgical safety and efficacy of PAC vs preoperative chemotherapy for LAGC.
METHODS
This retrospective study included 292 patients with LAGC who received either PAC (n = 92) or preoperative chemotherapy (n = 200) followed by radical gastrectomy between January 2019 and December 2022. Tumor regression, surgical outcomes, postoperative recovery, and survival were compared between groups. Subgroup analysis was performed to evaluate the role of indocyanine green (ICG) fluorescence guidance. Overall survival, progression-free survival, and disease-free survival were estimated using Kaplan-Meier method, and independent prognostic factors were identified by the Cox proportional hazards regression model.
RESULTS
The PAC group demonstrated significantly higher pathological complete response rates (28.3% vs 6.5%, P < 0.001) and major pathological response rates (45.7% vs 27.5%, P = 0.002). Despite the PAC regimen increased intraoperative blood loss (100 mL vs 80 mL, P < 0.001), R0 resection rates (92.4% vs 91.0%, P = 0.693) and postoperative complications (23.9% vs 28.0%, P = 0.463) were comparable. ICG fluorescence guidance in the PAC group reduced the open conversion rate (0% vs 19.4%, P = 0.015) and increased the lymph node yield (32 vs 24, P = 0.004). The PAC regimen was significantly associated with prolonged survival outcomes (log-rank P < 0.001) and was an independent prognostic predictor in multivariate analyses (P < 0.05).
CONCLUSION
The PAC regimen significantly improved the pathological response and survival of patients with LAGC, without compromising surgical safety. ICG fluorescence guidance along with the PAC regimen may further optimize surgical outcomes.
Core Tip: This retrospective study of 292 patients with locally advanced gastric cancer demonstrated that programmed cell death protein-1 inhibitors plus apatinib and chemotherapy (PAC) significantly improved tumor regression response and survival outcomes compared with preoperative chemotherapy as a neoadjuvant therapy. The PAC regimen increased intraoperative blood loss, but did not compromise other surgical outcomes or postoperative recovery. Indocyanine green fluorescence guidance in the PAC group reduced the open conversion rate and enhanced lymph node yield. The PAC regimen was an independent prognostic predictor on multivariate analyses. Overall, PAC appears to be a promising neoadjuvant treatment option for locally advanced gastric cancer.
