Pathologic Response and Outcomes After Neoadjuvant Chemotherapy in Gastric Cancer: A NCDB Analysis

BACKGROUND: Pathologic complete response (pCR) after neoadjuvant therapy has been associated with improved survival in several malignancies, but its prognostic value in gastric cancer remains unclear. METHODS: Using the National Cancer Database, we identified non-metastatic gastric adenocarcinoma patients diagnosed 2004-2021 treated with neoadjuvant chemotherapy followed by curative-intent resection. Patients receiving neoadjuvant radiation were excluded. We analyzed pCR rates, overall survival (OS), and factors associated with pCR using a generalized estimating equations model. Kaplan-Meier and Cox proportional hazards models were used to assess OS. Trends in pCR over time were evaluated with time-trend analysis. RESULTS: Among 7258 patients, 672 (9.3%) achieved pCR. Median OS was significantly higher in patients with pCR compared to those without (167.9 vs. 65.8 months, p < 0.001). Subgroup analysis of cT2N1 or higher stage patients revealed the highest survival in patients with both tumor and nodal pCR (median OS 181.8 months). Patients diagnosed after 2018 were more likely to achieve pCR (OR: 1.26, 95% CI: 1.07-1.49, p = 0.005), correlating with the adoption of the FLOT regimen. Completion of adjuvant therapy in patients who achieved pCR did not significantly improve OS. CONCLUSION: pCR is associated with significantly improved OS in gastric cancer, especially when both tumoral and nodal pCR are achieved. Increasing pCR rates in recent years may reflect the uptake of modern chemotherapy regimens, underscoring the value of neoadjuvant strategies.