Individualizing Neoadjuvant Treatment in Esophageal Cancer: A Real-World Comparison of CROSS and FLOT

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ID: 315779
2026
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Abstract
Abstract Background Esophageal cancer is an aggressive malignancy with high recurrence rates. In patients with locally advanced disease, neoadjuvant chemoradiotherapy according to the CROSS protocol followed by esophagectomy has long been the standard of care across histological subtypes. More recently, randomized trials such as ESOPEC suggested a potential survival benefit of perioperative chemotherapy with the FLOT regimen, particularly in adenocarcinoma. Aims To compare lymph node yield, pathological outcomes, and survival between FLOT and CROSS treatment strategies in a real-world cohort. Methods We retrospectively analyzed all patients who underwent curative esophagectomy at our institution between 2014 and 2025 and signed general consent. Results A total of 266 patients were included, of whom 231 (86.8%) had adenocarcinoma. Neoadjuvant treatment consisted of CROSS in 194 patients (73%), FLOT in 42 patients (16%), surgery alone in 23 patients (9%), and other regimens in 8 patients (3%). Patients treated with FLOT had a higher median lymph node yield compared to those treated with CROSS or without neoadjuvant therapy (34.0 vs. 26.0 vs. 30.0 nodes, respectively; p=0.08), this difference was even more pronounced and statistically significant in patients with adenocarcinoma. FLOT-treated patients more frequently presented with nodal-positive disease, inferior tumor regression, and higher pathological T-stages. Overall survival was superior in patients treated with CROSS compared to FLOT (median OS 62.0 vs. 28.0 months, p=0.003, Fig. 1). These findings were consistent when analysis was restricted to patients with adenocarcinoma. Conclusion Although limited by its retrospective nature, our data suggest that neoadjuvant chemoradiotherapy according to the CROSS protocol may be associated with more favorable pathological and survival outcomes compared to perioperative FLOT, both in the overall cohort and in patients with adenocarcinoma. Possible explanations include higher treatment completion rates with CROSS and differences in baseline performance status in this real-world population. Treatment decisions should therefore be individualized based on patient and tumor characteristics.Figure 1:Survival curves stratified by preoperative neoadjuvant therapy.For image description, please refer to the figure legend and surrounding text.
Reference Key
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Authors S Gerber, P Aeschbacher, D Kroell, M Berger, H Hemmatazad, Y Borbély
Journal the british journal of surgery
Year 2026
DOI
10.1093/bjs/znag055.065
URL
https://doi.org/10.1093/bjs/znag055.065
Keywords Keywords not found

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