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Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer

Standard

Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer : A Prospective Multicentre Validation Study. / Dyrskjøt, Lars; Reinert, Thomas; Algaba, Ferran; Christensen, Emil; Nieboer, Daan; Hermann, Gregers G; Mogensen, Karin; Beukers, Willemien; Marquez, Mirari; Segersten, Ulrika; Høyer, Søren; Ulhøi, Benedicte P; Hartmann, Arndt; Stöhr, Robert; Wach, Sven; Nawroth, Roman; Schwamborn, Kristina; Tulic, Cane; Simic, Tatjana; Junker, Kerstin; Harving, Niels; Petersen, Astrid C; Jensen, Jørgen B; Keck, Bastian; Grimm, Marc-Oliver; Horstmann, Marcus; Maurer, Tobias; Steyerberg, Ewout W; Zwarthoff, Ellen C; Real, Francisco X; Malats, Núria; Malmström, Per-Uno; Ørntoft, Torben F.

In: EUR UROL, Vol. 72, No. 3, 09.2017, p. 461-469.

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

Harvard

Dyrskjøt, L, Reinert, T, Algaba, F, Christensen, E, Nieboer, D, Hermann, GG, Mogensen, K, Beukers, W, Marquez, M, Segersten, U, Høyer, S, Ulhøi, BP, Hartmann, A, Stöhr, R, Wach, S, Nawroth, R, Schwamborn, K, Tulic, C, Simic, T, Junker, K, Harving, N, Petersen, AC, Jensen, JB, Keck, B, Grimm, M-O, Horstmann, M, Maurer, T, Steyerberg, EW, Zwarthoff, EC, Real, FX, Malats, N, Malmström, P-U & Ørntoft, TF 2017, 'Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer: A Prospective Multicentre Validation Study', EUR UROL, vol. 72, no. 3, pp. 461-469. https://doi.org/10.1016/j.eururo.2017.05.040

APA

Dyrskjøt, L., Reinert, T., Algaba, F., Christensen, E., Nieboer, D., Hermann, G. G., Mogensen, K., Beukers, W., Marquez, M., Segersten, U., Høyer, S., Ulhøi, B. P., Hartmann, A., Stöhr, R., Wach, S., Nawroth, R., Schwamborn, K., Tulic, C., Simic, T., ... Ørntoft, T. F. (2017). Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer: A Prospective Multicentre Validation Study. EUR UROL, 72(3), 461-469. https://doi.org/10.1016/j.eururo.2017.05.040

Vancouver

Dyrskjøt L, Reinert T, Algaba F, Christensen E, Nieboer D, Hermann GG et al. Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer: A Prospective Multicentre Validation Study. EUR UROL. 2017 Sep;72(3):461-469. https://doi.org/10.1016/j.eururo.2017.05.040

Bibtex

@article{d5fddc721d2d465491937c84a0e07e4b,
title = "Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer: A Prospective Multicentre Validation Study",
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.RESULTS AND LIMITATIONS: The progression score was significantly (p<0.001) associated with age, stage, grade, carcinoma in situ, bacillus Calmette-Gu{\'e}rin treatment, European Organisation for Research and Treatment of Cancer risk score, and disease progression. Univariate Cox regression analysis showed that patients molecularly classified as high risk experienced more frequent disease progression (hazard ratio 5.08, 95% confidence interval 2.2-11.6; p<0.001). Multivariable Cox regression models showed that the progression score added independent prognostic information beyond clinical and histopathological risk factors (p<0.001), with an increase in concordance statistic from 0.82 to 0.86. The progression score showed high correlation (R2=0.85) between paired fresh-frozen and formalin-fixed paraffin-embedded tumour specimens, supporting translation potential in the standard clinical setting. A limitation was the relatively low progression rate (5%, 37/750 patients).CONCLUSIONS: The 12-gene progression score had independent prognostic power beyond clinical and histopathological risk factors, and may help in stratifying NMIBC patients to optimise treatment and follow-up regimens.PATIENT SUMMARY: Clinical use of a 12-gene molecular test for disease aggressiveness may help in stratifying patients with non-muscle-invasive bladder cancer to optimal treatment regimens.",
keywords = "Aged, Area Under Curve, Biomarkers, Tumor, Disease Progression, Female, Genetic Predisposition to Disease, Humans, Kaplan-Meier Estimate, Male, Multivariate Analysis, Neoplasm Invasiveness, Phenotype, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, ROC Curve, Real-Time Polymerase Chain Reaction, Reproducibility of Results, Risk Factors, Time Factors, Urinary Bladder Neoplasms, Journal Article, Multicenter Study, Validation Studies, Research Support, Non-U.S. Gov't",
author = "Lars Dyrskj{\o}t and Thomas Reinert and Ferran Algaba and Emil Christensen and Daan Nieboer and Hermann, {Gregers G} and Karin Mogensen and Willemien Beukers and Mirari Marquez and Ulrika Segersten and S{\o}ren H{\o}yer and Ulh{\o}i, {Benedicte P} and Arndt Hartmann and Robert St{\"o}hr and Sven Wach and Roman Nawroth and Kristina Schwamborn and Cane Tulic and Tatjana Simic and Kerstin Junker and Niels Harving and Petersen, {Astrid C} and Jensen, {J{\o}rgen B} and Bastian Keck and Marc-Oliver Grimm and Marcus Horstmann and Tobias Maurer and Steyerberg, {Ewout W} and Zwarthoff, {Ellen C} and Real, {Francisco X} and N{\'u}ria Malats and Per-Uno Malmstr{\"o}m and {\O}rntoft, {Torben F}",
note = "Copyright {\textcopyright} 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.",
year = "2017",
month = sep,
doi = "10.1016/j.eururo.2017.05.040",
language = "English",
volume = "72",
pages = "461--469",
journal = "EUR UROL",
issn = "0302-2838",
publisher = "Elsevier",
number = "3",

}

RIS

TY - JOUR

T1 - Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer

T2 - A Prospective Multicentre Validation Study

AU - Dyrskjøt, Lars

AU - Reinert, Thomas

AU - Algaba, Ferran

AU - Christensen, Emil

AU - Nieboer, Daan

AU - Hermann, Gregers G

AU - Mogensen, Karin

AU - Beukers, Willemien

AU - Marquez, Mirari

AU - Segersten, Ulrika

AU - Høyer, Søren

AU - Ulhøi, Benedicte P

AU - Hartmann, Arndt

AU - Stöhr, Robert

AU - Wach, Sven

AU - Nawroth, Roman

AU - Schwamborn, Kristina

AU - Tulic, Cane

AU - Simic, Tatjana

AU - Junker, Kerstin

AU - Harving, Niels

AU - Petersen, Astrid C

AU - Jensen, Jørgen B

AU - Keck, Bastian

AU - Grimm, Marc-Oliver

AU - Horstmann, Marcus

AU - Maurer, Tobias

AU - Steyerberg, Ewout W

AU - Zwarthoff, Ellen C

AU - Real, Francisco X

AU - Malats, Núria

AU - Malmström, Per-Uno

AU - Ørntoft, Torben F

N1 - Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

PY - 2017/9

Y1 - 2017/9

N2 - 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.RESULTS AND LIMITATIONS: The progression score was significantly (p<0.001) associated with age, stage, grade, carcinoma in situ, bacillus Calmette-Guérin treatment, European Organisation for Research and Treatment of Cancer risk score, and disease progression. Univariate Cox regression analysis showed that patients molecularly classified as high risk experienced more frequent disease progression (hazard ratio 5.08, 95% confidence interval 2.2-11.6; p<0.001). Multivariable Cox regression models showed that the progression score added independent prognostic information beyond clinical and histopathological risk factors (p<0.001), with an increase in concordance statistic from 0.82 to 0.86. The progression score showed high correlation (R2=0.85) between paired fresh-frozen and formalin-fixed paraffin-embedded tumour specimens, supporting translation potential in the standard clinical setting. A limitation was the relatively low progression rate (5%, 37/750 patients).CONCLUSIONS: The 12-gene progression score had independent prognostic power beyond clinical and histopathological risk factors, and may help in stratifying NMIBC patients to optimise treatment and follow-up regimens.PATIENT SUMMARY: Clinical use of a 12-gene molecular test for disease aggressiveness may help in stratifying patients with non-muscle-invasive bladder cancer to optimal treatment regimens.

AB - 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.RESULTS AND LIMITATIONS: The progression score was significantly (p<0.001) associated with age, stage, grade, carcinoma in situ, bacillus Calmette-Guérin treatment, European Organisation for Research and Treatment of Cancer risk score, and disease progression. Univariate Cox regression analysis showed that patients molecularly classified as high risk experienced more frequent disease progression (hazard ratio 5.08, 95% confidence interval 2.2-11.6; p<0.001). Multivariable Cox regression models showed that the progression score added independent prognostic information beyond clinical and histopathological risk factors (p<0.001), with an increase in concordance statistic from 0.82 to 0.86. The progression score showed high correlation (R2=0.85) between paired fresh-frozen and formalin-fixed paraffin-embedded tumour specimens, supporting translation potential in the standard clinical setting. A limitation was the relatively low progression rate (5%, 37/750 patients).CONCLUSIONS: The 12-gene progression score had independent prognostic power beyond clinical and histopathological risk factors, and may help in stratifying NMIBC patients to optimise treatment and follow-up regimens.PATIENT SUMMARY: Clinical use of a 12-gene molecular test for disease aggressiveness may help in stratifying patients with non-muscle-invasive bladder cancer to optimal treatment regimens.

KW - Aged

KW - Area Under Curve

KW - Biomarkers, Tumor

KW - Disease Progression

KW - Female

KW - Genetic Predisposition to Disease

KW - Humans

KW - Kaplan-Meier Estimate

KW - Male

KW - Multivariate Analysis

KW - Neoplasm Invasiveness

KW - Phenotype

KW - Predictive Value of Tests

KW - Proportional Hazards Models

KW - Prospective Studies

KW - ROC Curve

KW - Real-Time Polymerase Chain Reaction

KW - Reproducibility of Results

KW - Risk Factors

KW - Time Factors

KW - Urinary Bladder Neoplasms

KW - Journal Article

KW - Multicenter Study

KW - Validation Studies

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.eururo.2017.05.040

DO - 10.1016/j.eururo.2017.05.040

M3 - SCORING: Journal article

C2 - 28583312

VL - 72

SP - 461

EP - 469

JO - EUR UROL

JF - EUR UROL

SN - 0302-2838

IS - 3

ER -