Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer

Hoeppner J, Brunner T, Schmoor C, Bronsert P, Kulemann B, Claus R, Utzolino S, Izbicki JR, Gockel I, Gerdes B, Ghadimi M, Reichert B, Lock JF, Bruns C, Reitsamer E, Schmeding M, Benedix F, Keck T, Folprecht G, Thuss-Patience P, Neumann UP, Pascher A, Imhof D, Daum S, Strieder T, Krautz C, Zimmermann S, Werner J, Mahlberg R, Illerhaus G, Grimminger P, Lordick F (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 392

Pages Range: 323-335

Journal Issue: 4

DOI: 10.1056/NEJMoa2409408

Abstract

Background The best multimodal approach for resectable locally advanced esophageal adenocarcinoma is unclear. An important question is whether perioperative chemotherapy is preferable to preoperative chemoradiotherapy. Methods In this phase 3, multicenter, randomized trial, we assigned in a 1:1 ratio patients with resectable esophageal adenocarcinoma to receive perioperative chemotherapy with FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) plus surgery or preoperative chemoradiotherapy (radiotherapy at a dose of 41.4 Gy and carboplatin and paclitaxel) plus surgery. Eligibility criteria included a primary tumor with a clinical stage of cT1 cN+, cT2-4a cN+, or cT2-4a cN0 disease, in which T indicates the size and extent of the tumor (higher numbers indicate a more advanced tumor), and N indicates the presence (N+) or absence (N0) of cancer spread to the lymph nodes, without evidence of metastatic spread. The primary end point was overall survival. Results From February 2016 through April 2020, we assigned 221 patients to the FLOT group and 217 patients to the preoperative-chemoradiotherapy group. With a median follow-up of 55 months, overall survival at 3 years was 57.4% (95% confidence interval [CI], 50.1 to 64.0) in the FLOT group and 50.7% (95% CI, 43.5 to 57.5) in the preoperative-chemoradiotherapy group (hazard ratio for death, 0.70; 95% CI, 0.53 to 0.92; P=0.01). Progression-free survival at 3 years was 51.6% (95% CI, 44.3 to 58.4) in the FLOT group and 35.0% (95% CI, 28.4 to 41.7) in the preoperative-chemoradiotherapy group (hazard ratio for disease progression or death, 0.66; 95% CI, 0.51 to 0.85). Among the patients who started the assigned treatment, grade 3 or higher adverse events were observed in 120 of 207 patients (58.0%) in the FLOT group and in 98 of 196 patients (50.0%) in the preoperative-chemoradiotherapy group. Serious adverse events were observed in 98 of 207 patients (47.3%) in the FLOT group and in 82 of 196 patients (41.8%) in the preoperative-chemoradiotherapy group. Mortality at 90 days after surgery was 3.1% in the FLOT group and 5.6% in the preoperative-chemoradiotherapy group. Conclusions Perioperative chemotherapy with FLOT led to improved survival among patients with resectable esophageal adenocarcinoma as compared with preoperative chemoradiotherapy.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Leipzig Germany (DE) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) Charité - Universitätsmedizin Berlin Germany (DE) Robert-Bosch-Krankenhaus Germany (DE) Universitätsklinikum des Saarlandes (UKS) Germany (DE) Klinikum der Universität München Germany (DE) Klinikum Mutterhaus der Borromäerinnen Germany (DE) Klinikum Stuttgart Germany (DE) Universitätsmedizin der Johannes Gutenberg-Universität Mainz Germany (DE) Universitätsklinikum Münster Germany (DE) Universität Bielefeld Germany (DE) Medizinische Universität Graz Austria (AT) Universitätsklinikum Freiburg Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) Universitätsklinikum Augsburg Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Università Vita-Salute San Raffaele (UniSR) Italy (IT) Johannes Wesling Klinikum Minden Germany (DE) Universitätsklinikum Göttingen Germany (DE) Universitätsklinikum Würzburg Germany (DE) Universitätsklinikum Köln Germany (DE) Sana Kliniken AG Germany (DE) Universität Witten/Herdecke Germany (DE) Universitätsklinikum Magdeburg A.ö.R. Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Universitätsklinikum Essen Germany (DE)

How to cite

APA:

Hoeppner, J., Brunner, T., Schmoor, C., Bronsert, P., Kulemann, B., Claus, R.,... Lordick, F. (2025). Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer. New England Journal of Medicine, 392(4), 323-335. https://doi.org/10.1056/NEJMoa2409408

MLA:

Hoeppner, Jens, et al. "Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer." New England Journal of Medicine 392.4 (2025): 323-335.

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