Abstract
Background: Gastric signet-ring cell carcinoma (GSRCC) is an aggressive gastric cancer subtype with limited evidence supporting the role of neoadjuvant chemotherapy (NAC). This study evaluated the impact of NAC on overall survival (OS) in a large, population-based cohort. Methods: We analyzed data from the SEER database (2011-2018), identifying patients aged 20-80 years with primary gastric tumors (C16.0-C16.9) and signet-ring cell histology who underwent curative-intent gastrectomy. Patients with metastatic disease, non-curative surgery, clinical Stage I, incomplete staging, or unknown survival were excluded. OS was assessed using Kaplan-Meier analysis and multivariable Cox regression. Subgroup analyses evaluated the interaction of NAC with tumor location and clinical stage. Results: A total of 978 patients met inclusion criteria; 436 (44.6%) received NAC. The 3- and 5-year OS rates were 43.9% and 38.3%, respectively. NAC was not associated with improved OS compared to surgery alone (5-year OS: 39.7% vs. 37.2%; log-rank p = 0.34) and was not an independent prognostic factor in multivariable analysis (p = 0.651). Independent predictors of worse OS included larger tumor size, advanced stage, positive nodal status, and Black race (all p < 0.05). Subgroup analysis indicated a survival benefit from NAC in patients with mid or distal gastric tumors (p < 0.001 for interaction). Conclusions: In this SEER-based analysis, NAC did not improve OS in the overall GSRCC population. However, selected subgroups may derive benefit, supporting a personalized approach to neoadjuvant therapy in GSRCC.