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Background <p>Neoadjuvant chemotherapy improves downstaging and survival in locally advanced gastric or esophagogastric junction adenocarcinoma (LAGC/EGJC), but the incremental benefit of adding programmed death-1 (PD-1) blockade and pragmatic perioperative biomarkers remain uncertain.</p> Methods <p>We conducted a retrospective cohort of patients with clinically staged cT2N + M0 or cT3–4bNanyM0 (IIa–IVa) LAGC/EGJC who received neoadjuvant PD-1 inhibitor plus chemotherapy or chemotherapy alone, followed by D2 gastrectomy. After one-to-one propensity score matching, pathological response, radiologic response, recurrence-free survival (RFS), overall survival (OS), and safety were compared between the two groups. Exploratory analyses assessed PD-L1 combined positive score (CPS), mismatch repair (MMR) status, blood-based indices (NLR, PLR, SII, PNI).</p> Results <p>From January 2018 to December 2024, 360 patients were analyzed (n = 180 per group) after matching. The rates of ORR (70.56% vs. 47.22%), pCR (20.56% vs. 6.67%), and MPR (36.67% vs. 11.67%) in the Treatment group were statistically higher than those in the Control group (all <i>P</i> &lt; 0.001). RFS and OS were prolonged with neoadjuvant PD-1 inhibitor plus chemotherapy at 1, 1.5, and 2&#xa0;years (RFS HR = 0.330, 0.263, 0.302; OS HR = 0.363, 0.305, 0.358) with comparable perioperative safety. CPS showed limited discrimination. In contrast, dMMR and low NLR individually associated with deeper pathological response and longer survival.</p> Conclusions <p>Neoadjuvant PD-1 inhibitor plus chemotherapy enhances tumor regression, facilitates downstaging, and confers early survival benefits with acceptable safety.</p>

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Neoadjuvant PD-1 inhibitors plus chemotherapy versus neoadjuvant chemotherapy alone in patients with resectable locally advanced gastric cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月17日

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  • Zhenshun Li,
  • Aqiang Fan,
  • Mian Wang,
  • Wei Zhou,
  • Jinqiang Liu,
  • Yan Miao,
  • Wanli Yang,
  • Lili Duan,
  • Liaoran Niu,
  • Shushang Liu,
  • Chenyang Wang,
  • Xi Chen,
  • Hanbing Wang,
  • Yu Han,
  • Liu Hong

摘要

Background

Neoadjuvant chemotherapy improves downstaging and survival in locally advanced gastric or esophagogastric junction adenocarcinoma (LAGC/EGJC), but the incremental benefit of adding programmed death-1 (PD-1) blockade and pragmatic perioperative biomarkers remain uncertain.

Methods

We conducted a retrospective cohort of patients with clinically staged cT2N + M0 or cT3–4bNanyM0 (IIa–IVa) LAGC/EGJC who received neoadjuvant PD-1 inhibitor plus chemotherapy or chemotherapy alone, followed by D2 gastrectomy. After one-to-one propensity score matching, pathological response, radiologic response, recurrence-free survival (RFS), overall survival (OS), and safety were compared between the two groups. Exploratory analyses assessed PD-L1 combined positive score (CPS), mismatch repair (MMR) status, blood-based indices (NLR, PLR, SII, PNI).

Results

From January 2018 to December 2024, 360 patients were analyzed (n = 180 per group) after matching. The rates of ORR (70.56% vs. 47.22%), pCR (20.56% vs. 6.67%), and MPR (36.67% vs. 11.67%) in the Treatment group were statistically higher than those in the Control group (all P < 0.001). RFS and OS were prolonged with neoadjuvant PD-1 inhibitor plus chemotherapy at 1, 1.5, and 2 years (RFS HR = 0.330, 0.263, 0.302; OS HR = 0.363, 0.305, 0.358) with comparable perioperative safety. CPS showed limited discrimination. In contrast, dMMR and low NLR individually associated with deeper pathological response and longer survival.

Conclusions

Neoadjuvant PD-1 inhibitor plus chemotherapy enhances tumor regression, facilitates downstaging, and confers early survival benefits with acceptable safety.