Perioperative Chemotherapy vs Neoadjuvant Chemoradiation in Esophageal Cancer

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For patients with locally advanced esophageal adenocarcinoma that can be treated with surgery, chemotherapy administered before and after surgery improved survival compared to chemoradiotherapy before surgery. The research was presented by Hoeppner et al at the 2024 ASCO Annual Meeting (Abstract LBA1).


The phase III ESOPEC clinical trial compared two treatment strategies for locally advanced esophageal adenocarcinoma that could be treated with surgery: the CROSS protocol, which consisted of chemoradiotherapy before surgery; and the FLOT protocol of chemotherapy before and after surgery. A total of 221 participants were assigned to the FLOT protocol arm and 217 participants were assigned to the CROSS protocol arm. The median age of the study participants was 63 years, and 89% of the participants were men.

Key Findings

For all study participants, 403 started some form of treatment and 371 went on to receive surgery (191 in the FLOT arm and 180 in the CROSS arm). In the 90 days after surgery, 4.3% of the participants had died (3.2% in the FLOT arm and 5.6% in the CROSS arm), and after a median follow-up of 55 months, 218 participants had died (97 in the FLOT arm and 121 in the CROSS arm). 

Median overall survival was 66 months in the FLOT arm and 37 months in the CROSS arm. At 3 years, participants who received FLOT had a 30% lower risk of dying than those who received CROSS. The 3-year overall survival rates were 57% for the FLOT arm and 51% in the CROSS arm.

Of the 359 participants whose tumor regression status was known, a pathologic complete response was achieved in 35 patients in the FLOT arm and 24 in the CROSS arm. 

“Many patients in the United States and Europe are still treated with the CROSS radiochemotherapy protocol. Our study shows that patients with resectable esophageal cancer should have FLOT chemotherapy before and after the operation in order to optimize the chance of curing their tumors in the long term,” said lead study author Jens Hoeppner, MD, FACS, FEBS, of University Medical Center OWL, University of Bielefeld, Detmold, Germany.

Next Steps

Researchers will study whether surgery can be avoided in patients that have a complete pathological response to treatment with the FLOT or CROSS protocols and show no growth during active surveillance.

ASCO Perspective

“There is considerable disagreement as to whether giving all adjuvant therapy upfront vs ‘sandwich’ adjuvant therapy before and after surgery is the better standard of care for locally advanced resectable esophageal cancer. This randomized clinical trial from Europe answers that question for patients similar to those in enrolled in the trial: preoperative plus postoperative chemotherapy provides better outcomes,” said Jennifer Tseng, MD, MPH, of Boston Medical Center.

Disclosure: This study was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation). For full disclosures of the study authors, visit

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