Perioperative FLOT versus neoadjuvant CROSS for esophageal adenocarcinoma: real-world validation of the ESOPEC trial from the German Cancer Registry Group

Objective: To validate the findings of the ESOPEC trial, which demonstrated the superiority of perioperative 5-FU, leucovorin, oxaliplatin, docetaxel (FLOT) chemotherapy over Chemoradiotherapy for Esophageal Cancer Followed by Surgery Study (CROSS) in patients with resectable locally advanced esophageal and gastroesophageal junction adenocarcinoma in a population-based real-world setting. Methods: This retrospective cohort study, using clinical registry data provided by the German Cancer Registry Group of the Society of German Tumor Centers, included patients with adenocarcinoma of the esophagus or gastroesophageal junction (cT1 cN + cM0 or cT2–4 cNx cM0) who received neoadjuvant FLOT or CROSS. Propensity score matching was employed to balance baseline characteristics. The primary endpoint was overall survival (OS). Secondary endpoints were achievement of pathological complete response (pCR), perioperative mortality, and long-term recurrence-free survival. Results: After propensity score matching, 1088 patients were included. There were no significant differences between the FLOT and CROSS groups in terms of baseline tumor characteristics. After surgery, CROSS was associated with lower ypT stages ( P = 0.011) and a tendency toward higher pCR (15.8% vs. 12.6%; P = 0.221). Despite these advantages, FLOT was associated with longer median OS (28.1 vs. 22.1 months; P = 0.0016) compared to CROSS. Moreover, FLOT was associated with lower 90-day postoperative mortality (5.1% vs. 10%; P = 0.036). The crude proportion of documented distant recurrence in the follow-up was lower after FLOT than after CROSS (28.3% vs. 35.1%; P = 0.019). Conclusion: Perioperative chemotherapy using FLOT was associated with longer OS, lower 90-day mortality, and a lower crude proportion of documented distant recurrence when compared with neoadjuvant chemoradiotherapy CROSS in locally advanced adenocarcinoma of the esophagus and gastroesophageal junction; these real-world findings are directionally consistent with the ESOPEC trial.