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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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Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups. / van Kessel, K. E. M.; van der Keur, K. A.; Dyrskjot, L.; Algaba, F.; Welvaart, N. Y. C.; Beukers, W.; Segersten, U.; Keck, B.; Maurer, T.; Simic, T.; Horstmann, M.; Grimm, M. O.; Hermann, G. G.; Mogensen, K.; Hartmann, A.; Harving, N.; Petersen, A. C.; Jensen, J. B.; Junker, K.; Boormans, J. L.; Real, F. X.; Malats, N.; Malmstrom, P. U.; Orntoft, T. F.; Zwarthoff, E. C.

In: CLIN CANCER RES, Vol. 24, No. 7, 2018, p. 1586-1593.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research

Harvard

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 2018, 'Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups', CLIN CANCER RES, vol. 24, no. 7, pp. 1586-1593. https://doi.org/10.1158/1078-0432.Ccr-17-2719

APA

van Kessel, K. E. M., van der Keur, K. A., Dyrskjot, L., Algaba, F., Welvaart, N. Y. C., Beukers, W., Segersten, U., Keck, B., Maurer, T., Simic, T., Horstmann, M., Grimm, M. O., Hermann, G. G., Mogensen, K., Hartmann, A., Harving, N., Petersen, A. C., Jensen, J. B., Junker, K., ... Zwarthoff, E. C. (2018). Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups. CLIN CANCER RES, 24(7), 1586-1593. https://doi.org/10.1158/1078-0432.Ccr-17-2719

Vancouver

van Kessel KEM, van der Keur KA, Dyrskjot L, Algaba F, Welvaart NYC, Beukers W et al. Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups. CLIN CANCER RES. 2018;24(7):1586-1593. https://doi.org/10.1158/1078-0432.Ccr-17-2719

Bibtex

@article{2c2c85846bda4391a38cba0218cfe194,
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. (c)2018 AACR.",
author = "{van Kessel}, {K. E. M.} and {van der Keur}, {K. A.} and L. Dyrskjot and F. Algaba and Welvaart, {N. Y. C.} and W. Beukers and U. Segersten and B. Keck and T. Maurer and T. Simic and M. Horstmann and Grimm, {M. O.} and Hermann, {G. G.} and K. Mogensen and A. Hartmann and N. Harving and Petersen, {A. C.} and Jensen, {J. B.} and K. Junker and Boormans, {J. L.} and Real, {F. X.} and N. Malats and Malmstrom, {P. U.} and Orntoft, {T. F.} and Zwarthoff, {E. C.}",
year = "2018",
doi = "10.1158/1078-0432.Ccr-17-2719",
language = "English",
volume = "24",
pages = "1586--1593",
journal = "CLIN CANCER RES",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
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, K. E. M.

AU - van der Keur, K. A.

AU - Dyrskjot, L.

AU - Algaba, F.

AU - Welvaart, N. Y. C.

AU - Beukers, W.

AU - Segersten, U.

AU - Keck, B.

AU - Maurer, T.

AU - Simic, T.

AU - Horstmann, M.

AU - Grimm, M. O.

AU - Hermann, G. G.

AU - Mogensen, K.

AU - Hartmann, A.

AU - Harving, N.

AU - Petersen, A. C.

AU - Jensen, J. B.

AU - Junker, K.

AU - Boormans, J. L.

AU - Real, F. X.

AU - Malats, N.

AU - Malmstrom, P. U.

AU - Orntoft, T. F.

AU - Zwarthoff, E. C.

PY - 2018

Y1 - 2018

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. (c)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. (c)2018 AACR.

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

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

M3 - SCORING: Journal article

VL - 24

SP - 1586

EP - 1593

JO - CLIN CANCER RES

JF - CLIN CANCER RES

SN - 1078-0432

IS - 7

ER -