Recurrence Patterns of Esophageal Adenocarcinoma in the Phase III ESOPEC Trial Comparing Perioperative Chemotherapy With Preoperative Chemoradiotherapy

J Jens Hoeppner (From Bielefeld University, Medical School and University Medical Center Ostwestfalen-Lippe, Campus Hospital Lippe, Detmold, Germany (J.H.); the Department of Radiation Oncology, Medical University of Graz, Graz, Austria (T.B.); the Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany (C.S.); the Institute of Surgical Pathology, University Medical Center Freiburg, Germany (P.B.); the Department of Surgery, University Medical Center Schleswig-Holstein–Campus Lübeck, Lübeck, Germany (B.K., T.K.); Comprehensive Cancer Center Augsburg, Faculty of Medicine, University of Augsburg, Augsburg, Germany (R.C.); the Department of General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany (S.U.); the Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg–Eppendorf, Hamburg, Germany (J.R.I.); the Department of Gastrointestinal Surgery, IRCCS San Raffaele Scientific Institute and San Raffaele Vita-Salute Universi...) C Claudia Schmoor (From Bielefeld University, Medical School and University Medical Center Ostwestfalen-Lippe, Campus Hospital Lippe, Detmold, Germany (J.H.); the Department of Radiation Oncology, Medical University of Graz, Graz, Austria (T.B.); the Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany (C.S.); the Institute of Surgical Pathology, University Medical Center Freiburg, Germany (P.B.); the Department of Surgery, University Medical Center Schleswig-Holstein–Campus Lübeck, Lübeck, Germany (B.K., T.K.); Comprehensive Cancer Center Augsburg, Faculty of Medicine, University of Augsburg, Augsburg, Germany (R.C.); the Department of General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany (S.U.); the Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg–Eppendorf, Hamburg, Germany (J.R.I.); the Department of Gastrointestinal Surgery, IRCCS San Raffaele Scientific Institute and San Raffaele Vita-Salute Universi...) T Thomas Brunner (From Bielefeld University, Medical School and University Medical Center Ostwestfalen-Lippe, Campus Hospital Lippe, Detmold, Germany (J.H.); the Department of Radiation Oncology, Medical University of Graz, Graz, Austria (T.B.); the Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany (C.S.); the Institute of Surgical Pathology, University Medical Center Freiburg, Germany (P.B.); the Department of Surgery, University Medical Center Schleswig-Holstein–Campus Lübeck, Lübeck, Germany (B.K., T.K.); Comprehensive Cancer Center Augsburg, Faculty of Medicine, University of Augsburg, Augsburg, Germany (R.C.); the Department of General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany (S.U.); the Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg–Eppendorf, Hamburg, Germany (J.R.I.); the Department of Gastrointestinal Surgery, IRCCS San Raffaele Scientific Institute and San Raffaele Vita-Salute Universi...) P Peter Bronsert P Patrick Sven Plum (Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, Leipzig, Germany) F Fabian Nimczewski (Bielefeld University, University Medical Center OWL, Campus Hospital Lippe, Detmold, Germany) Z Zsolt Madarasz (Bielefeld University, University Medical Center OWL, Campus Hospital Lippe, Detmold, Germany) F Florian Lordick (From Bielefeld University, Medical School and University Medical Center Ostwestfalen-Lippe, Campus Hospital Lippe, Detmold, Germany (J.H.); the Department of Radiation Oncology, Medical University of Graz, Graz, Austria (T.B.); the Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany (C.S.); the Institute of Surgical Pathology, University Medical Center Freiburg, Germany (P.B.); the Department of Surgery, University Medical Center Schleswig-Holstein–Campus Lübeck, Lübeck, Germany (B.K., T.K.); Comprehensive Cancer Center Augsburg, Faculty of Medicine, University of Augsburg, Augsburg, Germany (R.C.); the Department of General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany (S.U.); the Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg–Eppendorf, Hamburg, Germany (J.R.I.); the Department of Gastrointestinal Surgery, IRCCS San Raffaele Scientific Institute and San Raffaele Vita-Salute Universi...)

Abstract

The ESOPEC trial showed that perioperative chemotherapy with fluorouracil (FU)/leucovorin/oxaliplatin/docetaxel (FLOT) improved survival in patients with nonmetastatic esophageal adenocarcinoma compared with preoperative chemoradiotherapy with CROSS (41.4Gy/carboplatin/paclitaxel). For this analysis, patients from the ESOPEC trial who underwent tumor resection were eligible. The reported end points here include cause-specific mortality, recurrence-free survival (RFS), and sites of recurrence. Of the 438 patients enrolled in ESOPEC, 192 of 221 (86.9%) FLOT patients and 179 of 217 (82.5%) CROSS patients underwent tumor resection. After a median follow-up of 56 months, 178 experienced disease recurrence (81 FLOT; 97 CROSS) and 28 died without recurrence (12 FLOT; 16 CROSS). The 3-year RFS rate was 54.5% in FLOT patients versus 39.0% in CROSS patients (hazard ratio [HR], 0.67 [95% CI, 0.51 to 0.89]; P = .005). Locoregional recurrence occurred in 39 FLOT versus 32 CROSS patients (3-year cumulative incidences 20.2% v 17.4%, HR, 1.00 [95% CI, 0.62 to 1.61]; P = .99). Distant recurrence occurred in 64 FLOT versus 89 CROSS patients (3-year cumulative incidences 31.5% v 47.2%, HR, 0.59 [95% CI, 0.43 to 0.82]; P = .002). Compared with CROSS, perioperative chemotherapy with FLOT improved survival through better systemic tumor control with a reduction in distant tumor recurrences, while locoregional efficacy was similar.

Article Details

Volume / Issue Vol. 43, Issue 32
Published November 10, 2025
Pages 3451-3456
ISSN 0732-183X
Publisher Lippincott Williams & Wilkins

Journal Info

Journal of Clinical Oncology

Lippincott Williams & Wilkins

ISSN: 0732-183X Health Sciences

Authors (8)

J

Jens Hoeppner

From Bielefeld University, Medical School and University Medical Center Ostwestfalen-Lippe, Campus Hospital Lippe, Detmold, Germany (J.H.); the Department of Radiation Oncology, Medical University of Graz, Graz, Austria (T.B.); the Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany (C.S.); the Institute of Surgical Pathology, University Medical Center Freiburg, Germany (P.B.); the Department of Surgery, University Medical Center Schleswig-Holstein–Campus Lübeck, Lübeck, Germany (B.K., T.K.); Comprehensive Cancer Center Augsburg, Faculty of Medicine, University of Augsburg, Augsburg, Germany (R.C.); the Department of General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany (S.U.); the Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg–Eppendorf, Hamburg, Germany (J.R.I.); the Department of Gastrointestinal Surgery, IRCCS San Raffaele Scientific Institute and San Raffaele Vita-Salute Universi...

C

Claudia Schmoor

From Bielefeld University, Medical School and University Medical Center Ostwestfalen-Lippe, Campus Hospital Lippe, Detmold, Germany (J.H.); the Department of Radiation Oncology, Medical University of Graz, Graz, Austria (T.B.); the Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany (C.S.); the Institute of Surgical Pathology, University Medical Center Freiburg, Germany (P.B.); the Department of Surgery, University Medical Center Schleswig-Holstein–Campus Lübeck, Lübeck, Germany (B.K., T.K.); Comprehensive Cancer Center Augsburg, Faculty of Medicine, University of Augsburg, Augsburg, Germany (R.C.); the Department of General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany (S.U.); the Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg–Eppendorf, Hamburg, Germany (J.R.I.); the Department of Gastrointestinal Surgery, IRCCS San Raffaele Scientific Institute and San Raffaele Vita-Salute Universi...

T

Thomas Brunner

From Bielefeld University, Medical School and University Medical Center Ostwestfalen-Lippe, Campus Hospital Lippe, Detmold, Germany (J.H.); the Department of Radiation Oncology, Medical University of Graz, Graz, Austria (T.B.); the Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany (C.S.); the Institute of Surgical Pathology, University Medical Center Freiburg, Germany (P.B.); the Department of Surgery, University Medical Center Schleswig-Holstein–Campus Lübeck, Lübeck, Germany (B.K., T.K.); Comprehensive Cancer Center Augsburg, Faculty of Medicine, University of Augsburg, Augsburg, Germany (R.C.); the Department of General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany (S.U.); the Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg–Eppendorf, Hamburg, Germany (J.R.I.); the Department of Gastrointestinal Surgery, IRCCS San Raffaele Scientific Institute and San Raffaele Vita-Salute Universi...

P

Peter Bronsert

P

Patrick Sven Plum

Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, Leipzig, Germany

F

Fabian Nimczewski

Bielefeld University, University Medical Center OWL, Campus Hospital Lippe, Detmold, Germany

Z

Zsolt Madarasz

Bielefeld University, University Medical Center OWL, Campus Hospital Lippe, Detmold, Germany

F

Florian Lordick

From Bielefeld University, Medical School and University Medical Center Ostwestfalen-Lippe, Campus Hospital Lippe, Detmold, Germany (J.H.); the Department of Radiation Oncology, Medical University of Graz, Graz, Austria (T.B.); the Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany (C.S.); the Institute of Surgical Pathology, University Medical Center Freiburg, Germany (P.B.); the Department of Surgery, University Medical Center Schleswig-Holstein–Campus Lübeck, Lübeck, Germany (B.K., T.K.); Comprehensive Cancer Center Augsburg, Faculty of Medicine, University of Augsburg, Augsburg, Germany (R.C.); the Department of General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany (S.U.); the Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg–Eppendorf, Hamburg, Germany (J.R.I.); the Department of Gastrointestinal Surgery, IRCCS San Raffaele Scientific Institute and San Raffaele Vita-Salute Universi...