Patients with esophageal adenocarcinoma achieving pathological complete response show better outcomes with FLOT chemotherapy compared to CROSS chemoradiotherapy.

• FLOT patients had a significantly lower recurrence rate (8.8%) vs. CROSS (24.7%).
• Overall survival was much better in the FLOT group, with a hazard ratio of 0.34 after adjustment.

Surgeons should consider FLOT for better long-term survival and lower recurrence likelihood in eligible patients.

• Distant metastases were more common in the CROSS group, highlighting differing recurrence patterns.