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Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups
Erasmus MC, Erasmus MC Canc Inst, Dept Pathol, Rotterdam, Netherlands.;Erasmus MC, Erasmus MC Canc Inst, Dept Urol, Rotterdam, Netherlands..
Erasmus MC, Erasmus MC Canc Inst, Dept Pathol, Rotterdam, Netherlands..
Aarhus Univ Hosp, Dept Mol Med, Aarhus, Denmark..
Univ Autonoma Barcelona, Fundacio Puigvert, Sect Pathol, Barcelona, Spain..
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2018 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 24, no 7, p. 1586-1593Article in journal (Refereed) Published
Abstract [en]

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. (C) 2018 AACR.

Place, publisher, year, edition, pages
AMER ASSOC CANCER RESEARCH , 2018. Vol. 24, no 7, p. 1586-1593
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Urology and Nephrology
Identifiers
URN: urn:nbn:se:uu:diva-351679DOI: 10.1158/1078-0432.CCR-17-2719ISI: 000429050000010PubMedID: 29367430OAI: oai:DiVA.org:uu-351679DiVA, id: diva2:1213690
Funder
EU, FP7, Seventh Framework Programme, 201663Available from: 2018-06-05 Created: 2018-06-05 Last updated: 2018-06-05Bibliographically approved

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Segersten, UlrikaMalmström, Per-Uno

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