Objective To investigate the risk factors of pathological complete response (pCR) after neoadjuvant therapy for locally advanced gastric cancer (LAGC) and assess the value of gastric tumor markers for predicting pCR in LAGC patients.

Methods We retrospectively analyzed the clinical and pathological characteristics of 213 patients who underwent radical gastrectomy and gastric tumor marker analysis after neoadjuvant therapy at The Chinse PLA General Hospital First Medical Center, between January 2020 and April 2024 (20 and 193 cases in the pCR and non-pCR groups, respectively). The interrelationships among pCR, tumor markers, and clinicopathological features were compared, and independent risk factors for pCR were analyzed. A nomogram was constructed to predict the pCR.

Results Among 213 patients, 20 (9.4%) achieved pCR. Univariate analysis showed that age (P=0.067), tumor bed diameter (P<0.001), gastrin-17 levels (P=0.005), CA72-4 levels (P=0.073), pepsinogen ratio (P=0.024), and neoadjuvant immunotherapy (P=0.022) were strongly associated with pCR in LAGC patients. Multivariate analysis showed that neoadjuvant immunotherapy, CA72-4 levels<2.5 U/mL, gastrin-17 levels<1.48 pmol/L, and tumor bed diameter <2.85 cm were independent predictive factors for pCR in LAGC patients (P<0.05). These indicators were incorporated into a nomogram prediction model; an receiver operating characteristic curve (ROC) was plotted with an AUC (95% CI) of 0.863 (0.785–0.942). The calibration and decision curves suggested that the nomogram was well calibrated and had a good net benefit.

Conclusions Gastric tumor markers can effectively predict pCR after neoadjuvant therapy in LAGC patients. Our nomogram showed a good predictive ability for pCR. Thus, our findings can serve as a useful reference for clinical decision making for LAGC patients.