Endoscopy 2022; 54(02): 109-117
DOI: 10.1055/a-1399-4989
Original article

Individual risk calculator to predict lymph node metastases in patients with submucosal (T1b) esophageal adenocarcinoma: a multicenter cohort study

Annieke W. Gotink*
 1   Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands
,
 1   Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands
,
Fiebo J. C. ten Kate
 2   Department of Pathology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands
 3   Department of Pathology, Isala Clinics, Zwolle, the Netherlands
,
Daan Nieboer
 4   Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands
,
Lucia Suzuki
 2   Department of Pathology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands
,
Bas L. A. M. Weusten
 5   Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands
 6   Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands
,
Lodewijk A. A. Brosens
 7   Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands
,
Richard van Hillegersberg
 8   Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands
,
Lorenza Alvarez Herrero
 6   Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands
,
Cees A. Seldenrijk
 9   Department of Pathology, Pathology DNA, St. Antonius Hospital, Nieuwegein, the Netherlands
,
Alaa Alkhalaf
10   Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, the Netherlands
,
Freek C. P. Moll
 3   Department of Pathology, Isala Clinics, Zwolle, the Netherlands
,
Erik J. Schoon
11   Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, the Netherlands
,
Ineke van Lijnschoten
12   Department of Pathology, PAMM, Eindhoven, the Netherlands
,
Thjon J. Tang
13   Department of Gastroenterology and Hepatology, Ijsselland Hospital, Capelle aan den Ijssel, the Netherlands
,
Hans van der Valk
14   Department of Pathology, Ijselland Hospital, Capelle aan den Ijssel, the Netherlands
,
Wouter B. Nagengast
15   Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, the Netherlands
,
Gursah Kats-Ugurlu
16   Department of Pathology, University Medical Center Groningen, Groningen, the Netherlands
,
John T. M. Plukker
17   Department of Surgery, University Medical Center Groningen, Groningen, the Netherlands
,
Martin H. M. G. Houben
18   Department of Gastroenterology and Hepatology, Haga Teaching Hospital, Den Haag, the Netherlands
,
Jaap S. van der Laan
19   Department of Pathology, Haga Teaching Hospital, Den Haag, the Netherlands
,
Roos E. Pouw
20   Department of Gastroenterology and Hepatology, Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, Amsterdam, the Netherlands
,
Jacques J. G. H. M. Bergman
20   Department of Gastroenterology and Hepatology, Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, Amsterdam, the Netherlands
,
21   Department of Pathology, Amsterdam University Medical Centers, Amsterdam, the Netherlands
,
Mark I. van Berge Henegouwen
22   Department of Surgery, Amsterdam University Medical Centers, Amsterdam, the Netherlands
,
Bas P. L Wijnhoven
23   Department of Surgery, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands
,
Pieter Jan F. de Jonge
 1   Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands
,
Michael Doukas
 2   Department of Pathology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands
,
Marco J. Bruno
 1   Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands
,
Katharina Biermann**
 2   Department of Pathology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands
,
Arjun D. Koch**
 1   Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands
› Author Affiliations
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Abstract

Background Lymph node metastasis (LNM) is possible after endoscopic resection of early esophageal adenocarcinoma (EAC). This study aimed to develop and internally validate a prediction model that estimates the individual risk of metastases in patients with pT1b EAC.

Methods A nationwide, retrospective, multicenter cohort study was conducted in patients with pT1b EAC treated with endoscopic resection and/or surgery between 1989 and 2016. The primary end point was presence of LNM in surgical resection specimens or detection of metastases during follow-up. All resection specimens were histologically reassessed by specialist gastrointestinal pathologists. Subdistribution hazard regression analysis was used to develop the prediction model. The discriminative ability of this model was assessed using the c-statistic.

Results 248 patients with pT1b EAC were included. Metastases were seen in 78 patients, and the 5-year cumulative incidence was 30.9 % (95 % confidence interval [CI] 25.1 %–36.8 %). The risk of metastases increased with submucosal invasion depth (subdistribution hazard ratio [SHR] 1.08, 95 %CI 1.02–1.14, for every increase of 500 μm), lymphovascular invasion (SHR 2.95, 95 %CI 1.95–4.45), and for larger tumors (SHR 1.23, 95 %CI 1.10–1.37, for every increase of 10 mm). The model demonstrated good discriminative ability (c-statistic 0.81, 95 %CI 0.75–0.86).

Conclusions A third of patients with pT1b EAC experienced metastases within 5 years. The probability of developing post-resection metastases was estimated with a personalized predicted risk score incorporating tumor invasion depth, tumor size, and lymphovascular invasion. This model requires external validation before implementation into clinical practice.

* Co-first authors


** Co-last authors


Supplementary material



Publication History

Received: 13 July 2020

Accepted after revision: 24 February 2021

Accepted Manuscript online:
24 February 2021

Article published online:
04 May 2021

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