FLOT vs. CROSS in adenocarcinoma of the esophagus and gastroesophageal junction: External validation of the ESOPEC-trial using a population-based matched-cohort study

Background: The ESOPEC trial recently demonstrated a survival advantage of perioperative FLOT chemotherapy over neoadjuvant CROSS chemoradiation in patients with resectable esophageal and gastroesophageal junction adenocarcinoma. To validate these findings in a real-world setting, we conducted a population-based analysis using by the German Cancer Registry Group of the Society of German Tumor Centers ([Table 1]).

Table 1 

Parameter	N (% of total)		p- value
	CROSS	FLOT
Matched Cohort
Total number	260	260
Distant metastases			0.044
Distant metastases	88 (33.8)	66 (25.4)
No distant metastases	172 (66.2)	194 (74.6)
Local recurrences			0.4
Local recurrences	16 (6.2)	22 (8.5)
No local recurrence	244 (93.8)	238 (91.5)
Recurrence Group			0.029
local recurrence	9 (3.5)	9 (3.5)
Isolated distant metastasis	81 (31.2)	53 (20.4)
combined distant metastasis and local recurrence	7 (2.7)	13 (5.0)
No documented metastasis/recurrence	163 (62.7)	185 (71.2)

Methods: This retrospective cohort study, using clinical registry data provided by the German Cancer Registry Group, included patients with adenocarcinoma of the esophagus or gastroesophageal juntion (cT1cN+cM0 or cT2-4 cNx cM0) who received neoadjuvant FLOT or CROSS. Propensity score matching was performed to balance baseline characteristics.

Results: Following matching, there were no significant differences between the FLOT and CROSS groups in terms of age, sex, tumor location, or baseline tumor characteristics. After surgery, CROSS was associated with lower ypT stages (p=0.045) and a trendency towards more complete response rates (16.7% vs. 13.4% (not significant)). Despite these advantages, FLOT was associated with longer median overall survival (36.0 vs 25.5 months (p=0.002)) compared to CROSS. Moreover, FLOT was associated with lower 90-day postoperative mortality (6% vs 11%, p=0.001) and lower rates of distant recurrence in the follow up (25.4% vs 33.8%, p=0.044) when compared to CROSS ([Fig. 1] [2]).

Fig. 1  

Fig. 2  

Conclusion: In resectable locally advanced esophageal adenocarcinoma, the overall survival rate of perioperative chemotherapy with FLOT is superior to preoperative chemoradiotherapy (CROSS). The registry data of the German Cancer Registry Group confirm the findings of the ESOPEC study in real-world settings.

Abstracts

Präsentiert in der Sitzung: ACO: Studien, Standards und Strategien in der onkologischen Viszeralchirurgie

Donnerstag, 18. September 2025, 09:30 – 11:00, MZF 3

Publikationsverlauf

Artikel online veröffentlicht:
04. September 2025