Does perioperative FLOT increase cure rates in resectable esophageal adenocarcinoma? A mixture cure model analysis

Abstract

BACKGROUND: Translating trial findings to real-world cure rates for resectable oesophageal and gastroesophageal junction (GEJ) adenocarcinoma is critical. Standard endpoints like disease-free survival (DFS) may not distinguish durable cures from delayed recurrences. METHODS: This analysis of the AGAMENON-SEOM registry (NCT04958720) compared perioperative chemotherapy versus neoadjuvant chemoradiotherapy (nCRT). We estimated cure rates and analysed DFS and overall survival (OS) using mixture cure models and Cox proportional hazards models. RESULTS: In 500 patients, perioperative FLOT improved DFS (HR 0.60; p = 0.01) and OS (adjusted HR 0.63; p = 0.015) compared to CROSS-based nCRT. Notably, cure models confirmed a higher cure fraction for FLOT in high-risk subgroups (e.g., stage III, high neutrophil-to-lymphocyte ratio). While platinum-fluoropyrimidine-based nCRT ± immunotherapy yielded higher R0 and pathological complete response rates, its estimated cure rate was comparable to FLOT, both overall and across all subgroups. CONCLUSION: Cure is an informative endpoint in localised oesophageal cancer. In this registry analysis, perioperative FLOT was associated with higher cure rates than CROSS, particularly in high-risk subgroups. Exploratory findings suggest that alternative neoadjuvant strategies, such as those incorporating ICIs or FOLFOX, warrant further investigation.