Impact of total gastrectomy plus perioperative PD-1 inhibitors on survival in locally advanced gastric cancer

TL;DR

Adding the PD-1 inhibitor sintilimab to standard treatment for advanced stomach cancer improves survival and surgical outcomes without increasing severe side effects.

Contribution

Demonstrates that combining sintilimab with surgery and chemotherapy improves survival and surgical outcomes in locally advanced gastric cancer.

Findings

Patients receiving sintilimab had higher R0 resection, pCR, and MPR rates compared to controls.

The experimental group showed significantly better 3-year OS and DFS compared to the control group.

Adverse events were comparable between groups, with manageable immune-related side effects in the experimental group.

Abstract

The prognosis for locally advanced gastric cancer (LAGC) remains suboptimal with standard perioperative chemotherapy. Integrating PD-1 inhibitors into this regimen is a promising strategy requiring further validation.

To evaluate the efficacy and safety of total gastrectomy plus perioperative PD-1 inhibitor (Sintilimab) in the management of locally advanced gastric cancer (LAGC).

In this retrospective cohort study, 200 patients with LAGC undergoing total gastrectomy (January 2021 - November 2022) were categorized based on treatment received into an experimental group (perioperative sintilimab + XELOX, n=100) and a control group (perioperative XELOX alone, n=100).

The experimental group demonstrated the markedly higher rates of R0 resection rate (97%: 90%, P < 0.05), pCR (25%: 10%, P < 0.05), and MPR (35%: 20%, P < 0.05) as opposed to the control group. Survival analysis revealed significantly better outcomes in the experimental group: 3-year OS (48%: 30%, P = 0.009), median OS (34.7: 23.6 months, P = 0.004), 3-year DFS (40%: 25%, P = 0.001), and median DFS (30.4: 21.3 months, P = 0.007) Two groups showed no clinically relevant difference in the frequency of grade ≥3 therapy-related adverse events (56.0%: 51.0%, P > 0.05). Immune-related adverse outcomes in the experimental group were mainly grade 1–2 hypothyroidism and rash, which were relieved after symptomatic treatment.

Total gastrectomy combined with perioperative sintilimab +XELOX regimen for LAGC significantly improves radical surgery, pathological response rate and long-term survival, with a manageable safety profile, offering a potentially effective treatment strategy.

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