Pathologic complete response in gastric and gastroesophageal adenocarcinoma: Context-dependent survival and CNS-enriched recurrence.

Abstract

e16141 Background: Although pathologic complete response (pCR) after neoadjuvant therapy is associated with improved outcomes in gastric and gastroesophageal junction (GEJ) adenocarcinoma, whether its prognostic significance varies by tumor location, radiotherapy exposure, or systemic regimen remains unclear. In addition, recurrence patterns among complete responders have not been reassessed in contemporary cohorts. In this single-institution cohort, we investigate the prognostic significance of pCR across key disease and treatment contexts and evaluate recurrence patterns, including central nervous system (CNS) involvement. Methods: Patients receiving neoadjuvant therapy followed by R0 resection for gastric and GEJ adenocarcinoma between 1990 and 2024 were identified from a single-institution database. Final pathology classified patients as pCR (ypT0N0) or non-pCR (residual tumor with or without nodal disease, including ypT0N+). Analysis of overall survival (OS) was performed and stratified by tumor location and radiotherapy (RT) exposure and by systemic treatment (CRT, MAGIC-era chemotherapy, FLOT, IO±chemo). Results: Among 1783 patients receiving preoperative therapy, 1498 underwent R0 resection. The overall rate of pCR was 12.5% [n=187/1498], but differed across tumor location and RT exposure (gastric: 6.6% [n=44/670], GEJ+RT: 19.6% [n=123/629], GEJ-noRT: 10.1% [n=20/199]) and systemic regimen (CRT: 19.6%, MAGIC-era: 6%, FLOT-era: 9.1%, IO±chemo: 15.9%). pCR was associated with improved OS in gastric (HR: 0.36, p=0.001) and GEJ+RT (HR: 0.48, p<0.001), but not among GEJ-noRT (HR: 0.54, p=0.18). Notably, among gastric cancer patients achieving pCR, no disease-related deaths were reported. The survival benefit of pCR was strongest with CRT (HR: 0.48, p<0.001) and MAGIC-era regimens (HR: 0.45, p=0.01), while not statistically significant in FLOT (HR: 0.26, p=0.18). Complete responders experienced a significantly higher rate of CNS-involved failures relative to non-pCR (35% vs. 4.5% of recurrences, p<0.001), with enrichment primarily observed among GEJ+RT tumors. Other recurrence patterns (hematogenous, locoregional, peritoneal) and median time to relapse did not differ between groups. Conclusions: The prognostic value of pCR was not uniform across gastric and GEJ adenocarcinoma. Survival gains were greatest among gastric and radiated GEJ tumors, attenuated in non-radiated GEJ tumors and in FLOT, and accompanied by persistent enrichment of CNS-involved relapse among complete responders. Survival benefit of pCR by tumor location, radiation exposure, and treatment regimen. Stratum Subgroup HR CI p-value Site and Radiation Gastric 0.36 0.16–0.69 0.001 GEJ+RT 0.48 0.35–0.65 <0.001 GEJ-noRT 0.54 0.22–1.33 0.183 Treatment Regimen CRT 0.48 0.35–0.65 <0.001 MAGIC-era 0.45 0.25–0.83 0.01 FLOT-era 0.26 0.04–1.89 0.183 IO±chemo 0.52 0.40–0.67 <0.001