PD07.08. FLOT Regimen Over a Decade of Experience: Is This a Farewell?

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ID: 326218
2026
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Abstract
Abstract Topic Esophageal Cancer: Adjuvant and Neo-Adjuvant Therapies Background Since 2019, perioperative FLOT has been the standard treatment for locally advanced gastric and junctional adenocarcinoma, with superior survival and pathological response. ESOPEC confirmed its superiority over CROSS in esophageal disease, despite relevant toxicity. We evaluated real-world OS, DFS, and predictors of poor Mandard response after perioperative FLOT and surgery. Methods A retrospective cohort study at a single high-volume referral center was conducted, including 255 patients with locally advanced esophageal and junctional adenocarcinoma who underwent surgical resection between 2017 and 2024 after neoadjuvant FLOT. Baseline characteristics, perioperative oncological treatments, surgical data, postoperative outcomes, pathological findings and molecular profiles were collected. Follow-up data included recurrence and survival. Survival analyses were performed using Kaplan–Meier curves while bivariate and multivariate analyses were conducted through logistic regression, using Jamovi software. Results Overall, 73.7% of patients completed preoperative chemotherapy, while 15.2% did not complete the full perioperative FLOT regimen, including a postoperative mortality of 3%; the remaining patients received alternative adjuvant therapies. Treatment-related toxicities occurred in 7% of cases, and dose reductions were required in 84.6% of the 52 fully documented patients. Molecular profiling was available in 75.7% of patients, with HER2 and PD-L1 expression observed in 19.2% and 19.7%, respectively; follow-up data were missing in 4%. Pathological complete response was achieved in 8.23% of patients. Overall survival at 12 and 24 months was 78.8% and 59.6%, respectively, while disease-free survival was 63.9% and 53.1%. Poor pathological response (Mandard 4–5) was significantly associated with higher postoperative morbidity, signet ring cell histology, and junctional tumor location (all p<0.001), findings confirmed on multivariate analysis.Chemotherapy dose intensity and molecular markers were not associated with pathological response. Conclusion In our experience, most patients completed neoadjuvant FLOT and surgery with acceptable tolerability, leading to meaningful adjuvant completion rate. However, pathological complete response rates were lower than reported in literature. Although some factors correlated with higher Mandard scores, no reliable predictors of poor response emerged. These findings suggest FLOT alone may be insufficient in real-world practice, supporting the integration of novel strategies, particularly biomarker-guided immunotherapy.
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Authors Floriana Iannace, Silvia Battaglia, Francesco Puccetti, Silvia Foti, Elio Treppiedi, Lavinia Barbieri, Lorenzo Gozzini, Agnese Carresi, Lorenzo Cinelli, Filippo Ostinelli, Davide Locatelli, Ugo Elmore, Riccardo Rosati
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Journal diseases of the esophagus : official journal of the international society for diseases of the esophagus
Year 2026
DOI
10.1093/dote/doag077.130
URL
https://doi.org/10.1093/dote/doag077.130
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