EURURO Vol. 72 No. 3

461 476

Bladder Cancer
Prognostic Impact of a 12-gene Progression Score in
Non–muscle-invasive Bladder Cancer:
A Prospective Multicentre Validation Study
Lars Dyrskjøt Thomas Reinert Ferran Algaba Emil Christensen Daan Nieboer
Gregers G. Hermann Karin Mogensen Willemien Beukers Mirari Marquez
Ulrika Segersten Søren Høyer Benedicte P. Ulhøi Arndt Hartmann Robert Sto¨hr
Sven Wach Roman Nawroth Kristina Schwamborn Cane Tulic , Tatjana Simic
Kerstin Junker Niels Harving Astrid C. Petersen Jørgen B. Jensen Bastian Keck
Marc-Oliver Grimm Marcus Horstmann Tobias Maurer Ewout W. Steyerberg
Ellen C. Zwarthoff Francisco X. Real Nu´ria Malats Per-Uno Malmstro¨m
Torben F. Ørntoft
a Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; bSection of Pathology, Fundacio´ Puigvert, University Autonoma de
Barcelona, Barcelona, Spain; c Department of Public Health, Erasmus MC, Rotterdam, The Netherlands; d Department of Urology, Frederiksberg Hospital,
Frederiksberg, Denmark; e Department of Pathology, Erasmus MC, Rotterdam, The Netherlands; f Spanish National Cancer Research Centre, Madrid, Spain;
g Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; h Department of Pathology, Aarhus University Hospital, Aarhus, Denmark; i Institute
of Pathology, University Hospital Erlangen, Friedrich Alexander-University Erlangen-Nu¨rnberg, Erlangen, Germany; j Department of Urology, University
Hospital Erlangen, Friedrich Alexander-University Erlangen-Nu¨rnberg, Erlangen, Germany; k Department of Urology, Klinikum rechts der Isar, Technical
University of Munich, Munich, Germany; l Institute of Pathology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany; m Clinic of
Urology, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; n Institute of Medical and Clinical Biochemistry, Faculty of
Medicine, University of Belgrade, Belgrade, Serbia; oDepartment of Urology, Saarland University, Homburg, Germany; pDepartment of Urology, Aalborg
University Hospital, Aalborg, Denmark; qDepartment of Pathology, Aalborg University Hospital, Aalborg, Denmark; rDepartment of Urology, Aarhus
University Hospital, Aarhus, Denmark; s Department of Urology, Friedrich-Schiller-University Jena, Jena, Germany; t Departament de Cie`ncies Experimentals i
de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
ava ilable at
journal homepage:
Article info
Article history:
Accepted May 22, 2017
Associate Editor:
James Catto
Keywords:
Bladder cancer
Non–muscle-invasive bladder
cancer
Prognostic biomarker
Abstract
Background: Progression of non–muscle-invasive bladder cancer (NMIBC) to muscle-
invasive bladder cancer (MIBC) is life-threatening and cannot be accurately predicted
using clinical and pathological risk factors. Biomarkers for stratifying patients to
treatment and surveillance are greatly needed.
Objective: To validate a previously developed 12-gene progression score to predict
progression to MIBC in a large, multicentre, prospective study.
Design, setting, and participants: We enrolled 1224 patients in ten European centres
between 2008 and 2012. A total of 750 patients (851 tumours) fulfilled the inclusion and
sample quality criteria for testing. Patients were followed for an average of 28 mo (range
0–76). A 12-gene real-time qualitative polymerase chain reaction assay was performed
for all tumours and progression scores were calculated using a predefined formula and
cut-off values.
Outcome measurements and statistical analysis: We measured progression to MIBC
using Cox regression analysis and log-rank tests for comparing survival distributions.
* Corresponding author. Department of Molecular Medicine, Aarhus University Hospital, Palle
Juul-Jensens Boulevard, DK-8200 Aarhus N, Denmark. Tel. +45 78455320; Fax: +45 86782108.
E-mail address: (L. Dyrskjøt).
0302-2838/# 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.