Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer
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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, Jahrgang 72, Nr. 3, 09.2017, S. 461-469.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung
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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 -