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Impact of Extracapsular Lymph Node Involvement After Neoadjuvant Chemoradiation Therapy Followed by Surgery in Carcinoma of the Esophagus

A Multicenter Study

Depypere, Lieven P., MD*; Moons, Johnny, MSc*; Mariette, Christophe, PhD; D’Journo, Xavier B., PhD; Thomas, Pascal A., PhD; Hölscher, Arnulf H., PhD§; Bollschweiler, Elfriede, PhD§; van Berge-Henegouwen, Mark I., PhD; Van Lanschot, Jan J. B., PhD||; Lerut, Toni E. M. R., PhD*; Nafteux, Philippe R., PhD*

doi: 10.1097/SLA.0000000000002425

Objectives: The current study aims to examine the impact of extracapsular lymph node involvement (EC-LNI) on survival for both esophageal adenocarcinoma (AC) and squamous cell carcinoma (SCC) treated with neoadjuvant chemoradiation therapy (nCRT) followed by surgery.

Background: Studies have demonstrated the negative prognostic value of EC-LNI in primary surgery, but its impact after nCRT remains unclear.

Methods: From the databases of 6 European high-volume centers 1505 patients with R0 resections were withheld. Oncologic variables, including ypT, ypN, number of positive lymph nodes, and lymph node capsular status: EC-LNI and intracapsular lymph node involvement (IC-LNI), were examined. Statistical analysis was performed by Cox proportional hazards modeling.

Results: In SCC 182 patients (31.6%) had positive lymph nodes, of whom 60 (33.0%) showed EC-LNI. In AC 391 patients (42.1%) had positive lymph nodes, of whom 147 (37.6%) showed EC-LNI. Overall 5-year survival (O5YS) in SCC was 42.0%. Presence of EC-LNI meant a significantly worse O5YS than IC-LNI or pN0 (10.6%, 39.5%, and 47.4%, respectively; P < 0.05). O5YS in AC was 41.2%. No significant difference was observed between EC-LNI and IC-LNI (P = 0.322). In the multivariate analysis, among the examined possible prognosticators, presence of EC-LNI showed the highest hazard ratio (2.29, confidence interval: 1.52–3.47) as an independent prognosticator for overall survival in SCC, but it was not in AC.

Conclusions: Based on this international multicenter study, the presence of EC-LNI after nCRT is at least as important as N-stage for survival and EC-LNI is the strongest prognosticator for overall survival in SCC but not in AC.

*Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium

Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, Lille, France

Department of Thoracic Surgery and Surgery of the Esophagus, Aix-Marseille University and Assistance Publique-Hôpitaux de Marseille, Marseille, France

§Klinik und Poliklinik für Allgemein-, Viszeral- und Tumorchirurgie, Cologne, Germany

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

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

Reprints: Lieven P. Depypere, MD, Department of Thoracic Surgery, University Hospital Leuven, Herestraat 49, 3000 Leuven, Belgium. E-mail:

The authors report no conflict of interests. Christophe Mariette is deceased.

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