Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Van Kessel KEM, Van Der Keur KA, Dyrskjot L, Algaba F, Welvaart NYC, Beukers W, Segersten U, Keck B, Maurer T, Simic T, Horstmann M, Grimm MO, Hermann GG, Mogensen K, Hartmann A, Harving N, Petersen AC, Jensen JB, Junker K, Boormans JL, Real FX, Malats N, Malmstrom PU, Orntoft TF, Zwarthoff EC
Zeitschrift: Clinical Cancer Research
Jahr der Veröffentlichung: 2018
Band: 24
Heftnummer: 7
Seitenbereich: 1586-1593
ISSN: 1078-0432


Abstract

Purpose: The European Association of Urology (EAU) guidelines for non-muscle-invasive bladder cancer (NMIBC) recommend risk stratification based on clinicopathologic parameters. Our aim was to investigate the added value of biomarkers to improve risk stratification of NMIBC.Experimental Design: We prospectively included 1,239 patients in follow-up for NMIBC in six European countries. Fresh-frozen tumor samples were analyzed for GATA2, TBX2, TBX3, and ZIC4 methylation and FGFR3, TERT, PIK3CA, and RAS mutation status. Cox regression analyses identified markers that were significantly associated with progression to muscle-invasive disease. The progression incidence rate (PIR = rate of progression per 100 patient-years) was calculated for subgroups.Results: In our cohort, 276 patients had a low, 273 an intermediate, and 555 a high risk of tumor progression based on the EAU NMIBC guideline. Fifty-seven patients (4.6%) progressed to muscle-invasive disease. The limited number of progressors in this large cohort compared with older studies is likely due to improved treatment in the past two decades. Overall, wild-type FGFR3 and methylation of GATA2 and TBX3 were significantly associated with progression (HR = 0.34, 2.53, and 2.64, respectively). The PIR for EAU high-risk patients was 4.25. On the basis of FGFR3 mutation status and methylation of GATA2, this cohort could be reclassified into a good class (PIR = 0.86, 26.2% of patients), a moderate class (PIR = 4.32, 49.7%), and a poor class (PIR = 7.66, 24.0%).Conclusions: We conclude that the addition of selected biomarkers to the EAU risk stratification increases its accuracy and identifies a subset of NMIBC patients with a very high risk of progression. Clin Cancer Res; 24(7); 1586-93. ©2018 AACR.


FAU-Autoren / FAU-Herausgeber

Hartmann, Arndt Prof. Dr. med.
Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie
Keck, Bastian PD Dr.
Medizinische Fakultät


Autor(en) der externen Einrichtung(en)
Aalborg University
Aarhus University Hospital / Aarhus Universitetshospital
Autonomous University of Barcelona (UAB) / Universitat Autònoma de Barcelona
Centro de Investigación Biomédica en Red (CIBER)
Erasmus University Medical Center
Friedrich-Schiller-Universität Jena
Technische Universität München (TUM)
Universität des Saarlandes (UdS)
University of Belgrade / Универзитет у Београду
University of Copenhagen
Uppsala University


Zitierweisen

APA:
Van Kessel, K.E.M., Van Der Keur, K.A., Dyrskjot, L., Algaba, F., Welvaart, N.Y.C., Beukers, W.,... Zwarthoff, E.C. (2018). Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups. Clinical Cancer Research, 24(7), 1586-1593. https://dx.doi.org/10.1158/1078-0432.CCR-17-2719

MLA:
Van Kessel, Kim E. M., et al. "Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups." Clinical Cancer Research 24.7 (2018): 1586-1593.

BibTeX: 

Zuletzt aktualisiert 2018-08-11 um 21:08