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

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Harvard

van Kessel, KEM, van der Keur, KA, Dyrskjøt, L, Algaba, F, Welvaart, NYC, Beukers, W, Segersten, U, Keck, B, Maurer, T, Simic, T, Horstmann, M, Grimm, M-O, Hermann, GG, Mogensen, K, Hartmann, A, Harving, N, Petersen, AC, Jensen, JB, Junker, K, Boormans, JL, Real, FX, Malats, N, Malmström, P-U, Ørntoft, TF & Zwarthoff, EC 2018, 'Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups' Clinical Cancer Research, bind 24, nr. 7, s. 1586-1593. https://doi.org/10.1158/1078-0432.CCR-17-2719

APA

van Kessel, K. E. M., van der Keur, K. A., Dyrskjøt, 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://doi.org/10.1158/1078-0432.CCR-17-2719

CBE

van Kessel KEM, van der Keur KA, Dyrskjøt L, Algaba F, Welvaart NYC, Beukers W, Segersten U, Keck B, Maurer T, Simic T, Horstmann M, Grimm M-O, Hermann GG, Mogensen K, Hartmann A, Harving N, Petersen AC, Jensen JB, Junker K, Boormans JL, Real FX, Malats N, Malmström P-U, Ørntoft TF, Zwarthoff EC. 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://doi.org/10.1158/1078-0432.CCR-17-2719

MLA

Vancouver

Author

van Kessel, Kim E M ; van der Keur, Kirstin A ; Dyrskjøt, Lars ; Algaba, Ferran ; Welvaart, Naeromy Y C ; Beukers, Willemien ; Segersten, Ulrika ; Keck, Bastian ; Maurer, Tobias ; Simic, Tatjana ; Horstmann, Marcus ; Grimm, Marc-Oliver ; Hermann, Gregers G ; Mogensen, Karin ; Hartmann, Arndt ; Harving, Niels ; Petersen, Astrid C ; Jensen, Jørgen B ; Junker, Kerstin ; Boormans, Joost L ; Real, Francisco X ; Malats, Núria ; Malmström, Per-Uno ; Ørntoft, Torben F ; Zwarthoff, Ellen C. / Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups. I: Clinical Cancer Research. 2018 ; Bind 24, Nr. 7. s. 1586-1593.

Bibtex

@article{a11b8587fb974a8391a4d16595435033,
title = "Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups",
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. {\circledC}2018 AACR.",
author = "{van Kessel}, {Kim E M} and {van der Keur}, {Kirstin A} and Lars Dyrskj{\o}t and Ferran Algaba and Welvaart, {Naeromy Y C} and Willemien Beukers and Ulrika Segersten and Bastian Keck and Tobias Maurer and Tatjana Simic and Marcus Horstmann and Marc-Oliver Grimm and Hermann, {Gregers G} and Karin Mogensen and Arndt Hartmann and Niels Harving and Petersen, {Astrid C} and Jensen, {J{\o}rgen B} and Kerstin Junker and Boormans, {Joost L} and Real, {Francisco X} and N{\'u}ria Malats and Per-Uno Malmstr{\"o}m and {\O}rntoft, {Torben F} and Zwarthoff, {Ellen C}",
note = "{\circledC}2018 American Association for Cancer Research.",
year = "2018",
month = "4",
day = "1",
doi = "10.1158/1078-0432.CCR-17-2719",
language = "English",
volume = "24",
pages = "1586--1593",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research (A A C R)",
number = "7",

}

RIS

TY - JOUR

T1 - Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups

AU - van Kessel, Kim E M

AU - van der Keur, Kirstin A

AU - Dyrskjøt, Lars

AU - Algaba, Ferran

AU - Welvaart, Naeromy Y C

AU - Beukers, Willemien

AU - Segersten, Ulrika

AU - Keck, Bastian

AU - Maurer, Tobias

AU - Simic, Tatjana

AU - Horstmann, Marcus

AU - Grimm, Marc-Oliver

AU - Hermann, Gregers G

AU - Mogensen, Karin

AU - Hartmann, Arndt

AU - Harving, Niels

AU - Petersen, Astrid C

AU - Jensen, Jørgen B

AU - Junker, Kerstin

AU - Boormans, Joost L

AU - Real, Francisco X

AU - Malats, Núria

AU - Malmström, Per-Uno

AU - Ørntoft, Torben F

AU - Zwarthoff, Ellen C

N1 - ©2018 American Association for Cancer Research.

PY - 2018/4/1

Y1 - 2018/4/1

N2 - 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.

AB - 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.

U2 - 10.1158/1078-0432.CCR-17-2719

DO - 10.1158/1078-0432.CCR-17-2719

M3 - Journal article

VL - 24

SP - 1586

EP - 1593

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 7

ER -

ID: 54774577