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Impact of Surgical Approach on Long-term Survival in Esophageal Adenocarcinoma Patients With or Without Neoadjuvant Chemoradiotherapy

Noordman, Bo, Jan, MD*; van Klaveren, David, PhD; van Berge Henegouwen, Mark, I., MD PhD; Wijnhoven, Bas P., L., MD, PhD*; Gisbertz, Suzanne, S., MD, PhD; Lagarde, Sjoerd, M., MD, PhD*,‡; van der Gaast, Ate, MD, PhD§; Hulshof, Maarten C. C., M., MD, PhD; Biermann, Katharina, MD, PhD||; Steyerberg, Ewout, W., MD, PhD; van Lanschot, J. Jan, B., MD, PhD*also on behalf of the CROSS-study group

doi: 10.1097/SLA.0000000000002240
Original Articles

Objective: To compare overall survival in patients with esophageal adenocarcinoma who underwent transhiatal esophagectomy (THE) with limited lymphadenectomy or transthoracic esophagectomy (TTE) with extended lymphadenectomy with or without neoadjuvant chemoradiotherapy (nCRT).

Background: The application of neoadjuvant therapy might change the association between the extent of lymphadenectomy and survival in patients with esophageal adenocarcinoma. This may influence the choice of surgical approach in patients treated with nCRT.

Methods: Patients with potentially curable subcarinal esophageal adenocarcinoma treated with surgery alone or nCRT followed by surgery in 7 centers were included. The effect of surgical approach on overall survival, differentiated by the addition or omission of nCRT, was analyzed using a multivariable Cox regression model that included well-known prognostic factors and factors that might have influenced the choice of surgical approach.

Results: In total, 701 patients were included, of whom 318 had TTE with extended lymphadenectomy and 383 had THE with limited lymphadenectomy. TTE had differential effects on survival (P for interaction = 0.02), with a more favorable prognostic effect in patients who were treated with surgery alone [hazard ratio (HR) = 0.77, 95% confidence interval (CI) 0.58–1.03]. This association was statistically significant in a subgroup of patients with 1 to 8 positive lymph nodes in the resection specimen (HR = 0.62, 95% CI 0.43–0.90). The favorable prognostic effect of TTE over THE was absent in the nCRT and surgery group (HR = 1.16, 95% CI 0.80–1.66) and in the subgroup of nCRT patients with 1 to 8 positive lymph nodes in the resection specimen (HR = 1.00, 95% CI 0.61–1.68).

Conclusions: Compared to surgery alone, the addition of nCRT may reduce the need for TTE with extended lymphadenectomy to improve long-term survival in patients with esophageal adenocarcinoma.

*Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands

Department of Public Health, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands

Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands

§Department of Medical Oncology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands

Department of Radiation Oncology, Academic Medical Center, Amsterdam, The Netherlands

||Department of Pathology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

Reprints: Bo Jan Noordman, MD, Department of Surgery, Erasmus MC University Medical Center, Suite H-822k, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. E-mail: b.noordman@erasmusmc.nl.

Collaborators List: The authors acknowledge the prior work by the members of the CROSS study group: Joël Shapiro, MD, Department of Surgery, Erasmus MC University Medical Center Rotterdam; Pieter van Hagen, MD, Department of Surgery, Erasmus MC University Medical Center, Rotterdam; Hanneke W. M. van Laarhoven, MD, PhD, Department of Medical Oncology, Academic Medical Center, Amsterdam; Grard A.P. Nieuwenhuijzen, MD, PhD, Department of Surgery, Catharina Hospital, Eindhoven; Geke A.P. Hospers, MD, PhD, Department of Medical Oncology, University Medical Center Groningen, Groningen; Johannes J. Bonenkamp, MD, PhD, Department of Surgery, Radboud University Medical Center, Nijmegen; Miguel A. Cuesta, MD, PhD, formerly Department of Surgery, VU Medical Center, Amsterdam; Reinoud J.B. Blaisse, MD, Department of Medical Oncology, Rijnstate Hospital, Arnhem; Olivier R.C. Busch, MD, PhD, Department of Surgery, Academic Medical Center, Amsterdam; Fiebo J.W. ten Kate, MD, PhD formerly Department of Pathology, Academic Medical Center, Amsterdam; Geert-Jan Creemers, MD, PhD, Department of Medical Oncology, Catharina Hospital, Eindhoven; Cornelis J.A. Punt, MD, PhD, Department of Medical Oncology, formerly Radboud University Medical Center, Nijmegen, currently Department of Medical Oncology, Academic Medical Center, Amsterdam; John T.M. Plukker, MD, PhD, Department of Surgery, University Medical Center Groningen, Groningen; Henk M.W. Verheul, MD, PhD, Department of Medical Oncology, VU Medical Center, Amsterdam; Ernst J. Spillenaar Bilgen, MD, PhD, Department of Surgery, Rijnstate Hospital, Arnhem; Herman van Dekken, MD, PhD, formerly Department of Pathology, Erasmus MC University Medical Center, Rotterdam; Maurice J.C. van der Sangen, MD, PhD, Department of Radiation Oncology, Catharina Hospital, Eindhoven; Tom Rozema, MD, Department of Radiation Oncology, Radboud University Medical Center, Nijmegen and Verbeeten Institute Tilburg, Tilburg; Jannet C. Beukema, MD, Department of Radiation Oncology, University Medical Center Groningen, Groningen; Anna H.M. Piet, MD, Department of Radiation Oncology, VU Medical Center, Amsterdam; Caroline M. van Rij, MD, Department of Radiation Oncology, Erasmus MC University Medical Center, Rotterdam; Janny G. Reinders, MD, formerly Arnhem Radiotherapeutic Institute ARTI, Arnhem; Hugo W. Tilanus, MD, PhD formerly Department of Surgery, Erasmus MC University Medical Center, Rotterdam.

The authors report no conflicts of interest.

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