Clinical outcomes of extended neoadjuvant FLOT for resectable gastroesophageal cancer.

Abstract

356 Background: FLOT4 and ESOPEC established 4 preoperative/4 postoperative cycles of FLOT as the standard of care for nonmetastatic gastroesophageal adenocarcinomas, but <50% of patients are able to complete the full chemotherapeutic regimen, particularly the postoperative portion. It is unclear if failing to receive adequate systemic therapy has any bearing on disease-free and overall survival for these patients. In this study, we aimed to assess if delivering more preoperative doses (≥6) of chemotherapy has any drawbacks and whether outcomes are more favorable than the standard approach. Methods: Review of Moffitt’s IRB-approved esophagectomy (1994-2025) and gastrectomy (2000-2025) databases identified 19 esophageal and 77 gastric cancer patients receiving perioperative chemotherapy without radiation. Demographics, clinical characteristics, and survival were compared between patients planned to receive 4 preoperative cycles (cohort A) and those planned for ≥6 (cohort B) using Chi-Square, Wilcoxon rank-sum, two-sample t-test, and Kaplan-Meier survival analyses. Results: Of the total 96 patients, 33 (34.4%) received ≤4 preoperative cycles while 63 (65.6%) received ≥6. Median age, gender, race, Charlson Comorbidity Index score, smoking status, and primary tumor type were similar between groups (all p>0.05). Clinical T stage was more advanced in cohort B compared to A (p=0.05). Six patients in cohort B were de-escalated from FLOT to FOLFOX (9.5% vs 0%; p=0.07). There were no differences in postoperative complication rates (31.7% vs 21.2%; p=0.28), length of stay (6 vs 7 days; p=0.93), and negative surgical margin rates (96.8% vs 100%; p=0.30). Patients receiving more preoperative chemotherapy were more likely to complete the treatment course (58.7% vs 30.3%; p=0.008) and received a greater total number of cycles overall (8 vs 6; p≤0.001). The groups had similar recurrence rates (7.9% vs 9.1%; p=0.85), overall survival (HR = 1.13, 95% CI: 0.31, 4.05; p=0.9), and disease-free survival (HR = 0.99, 95% CI: 0.31, 3.15; p>0.9), despite a trend toward a higher pathological complete response (pCR) rate for cohort B (26.7% vs 13.8%; p=0.10). Conclusions: In our analysis, extended neoadjuvant chemotherapy increased treatment completion without worsening postsurgical outcomes. Although pCR rates were approximately doubled in the extended neoadjuvant group, the cohort size was insufficient for statistical significance. It is unclear if de-escalation of chemotherapy negates some benefits of FLOT administered for limited doses.