Immunoscore and Post-Neoadjuvant Pathological Features in Microsatellite-Stable Locally Advanced Gastric Cancer: A Retrospective Cohort Study

Background/Objectives: Pathological response after neoadjuvant chemotherapy is an established prognostic factor in locally advanced gastric cancer, but it does not fully reflect the biological heterogeneity of residual disease. The immune microenvironment may provide additional prognostic information. We therefore investigated the relationship between post-neoadjuvant Immunoscore, pathological findings, and disease-free survival in patients with microsatellite-stable locally advanced gastric cancer. Methods: This retrospective, single-center study included patients with locally advanced gastric adenocarcinoma who received four cycles of neoadjuvant FLOT followed by curative-intent gastrectomy between November 2023 and May 2025. Immunoscore was determined in post-neoadjuvant resection specimens based on CD3+ and CD8+ T-cell infiltration in the tumor center and invasive margin. Immunoscore assessments were performed by two pathologists blinded to clinical and outcome data, with final evaluations established through consensus review. Associations between Immunoscore and clinicopathological features were examined, including exploratory multivariable analyses adjusting for baseline clinical T stage and histological subtype. Disease-free survival was analyzed using the Kaplan–Meier method and Cox proportional hazards regression. Results: The final analysis included 48 patients. Compared with the low-Immunoscore group, the high-Immunoscore group had lower rates of ypT4 disease (37.5% vs. 75.0%; p = 0.014), ypN3 disease (21.9% vs. 68.8%; p = 0.002), and perineural invasion (43.8% vs. 75.0%; p = 0.041). The association between low Immunoscore and ypN3 disease persisted after adjustment for baseline clinical T stage and histological subtype (adjusted OR 5.89, 95% CI 1.32–26.23; p = 0.020). Tumor regression grade did not differ significantly between the groups (p = 0.211). During a median follow-up of 18.0 months, 17 patients developed recurrence. Disease-free survival was numerically longer in the high-Immunoscore group. The difference was not significant by the log-rank test (p = 0.100), whereas an exploratory Breslow analysis showed a difference between the survival distributions (p = 0.025). However, Cox regression did not demonstrate a statistically significant association with disease-free survival (HR 0.47, 95% CI 0.18–1.21; p = 0.117). Conclusions: A higher post-neoadjuvant Immunoscore was associated with less advanced residual tumor and nodal disease and less frequent perineural invasion, without a statistically significant association with tumor regression grade or disease-free survival in the primary analyses. Immunoscore may therefore complement conventional pathological assessment after neoadjuvant FLOT. These findings require validation in larger prospective cohorts.