TY - JOUR

T1 - ERG Protein Expression in Diagnostic Specimens Is Associated with Increased Risk of Progression During Active Surveillance for Prostate Cancer

AU - Berg, Kasper Drimer

AU - Vainer, Ben

AU - Thomsen, Frederik Birkebæk

AU - Røder, Martin Andreas

AU - Gerds, Thomas Alexander

AU - Toft, Birgitte Grønkær

AU - Brasso, Klaus

AU - Iversen, Peter

N1 - Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

PY - 2014/3/7

Y1 - 2014/3/7

N2 - BACKGROUND: Compelling biomarkers identifying prostate cancer patients with a high risk of progression during active surveillance (AS) are needed.OBJECTIVE: To examine the association between ERG expression at diagnosis and the risk of progression during AS.DESIGN, SETTING, AND PARTICIPANTS: This study included 265 patients followed on AS with prostate-specific antigen (PSA) measurements, clinical examinations, and 10-12 core rebiopsies from 2002 to 2012 in a prospectively maintained database. ERG immunohistochemical staining was performed on diagnostic paraffin-embedded formalin-fixed sections with a ready-to-use kit (anti-ERG, EPR3864). Men were characterised as ERG positive if a minimum of one tumour focus demonstrated ERG expression.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall AS progression was defined as clinical progression: increased clinical tumour category ≥cT2b by digital rectal examination and ultrasound, and/or histopathologic progression: upgrade of Gleason score, more than three positive cores or bilateral positive cores, and/or PSA progression: PSA doubling time <3 yr. Risk of progression was analysed using multiple cause-specific Cox regression and stratified cumulative incidences (Aalen-Johansen method). Curatively intended treatment, watchful waiting, and death without progression were treated as competing events.RESULTS AND LIMITATIONS: A total of 121 of 142 ERG-negative and 96 of 123 ERG-positive patients had complete diagnostic information. In competing risk models, the ERG-positive group showed significantly higher incidences of overall AS progression (p<0.0001) and of the subgroups PSA progression (p<0.0001) and histopathologic progression (p<0.0001). The 2-yr cumulative incidence of overall AS progression was 21.7% (95% confidence interval [CI], 14.3-29.1) in the ERG-negative group compared with 58.6% (95% CI, 48.7-68.5) in the ERG-positive group. ERG positivity was a significant predictor of overall AS progression in multiple Cox regression (hazard ratio: 2.45; 95% CI, 1.62-3.72; p<0.0001). The main limitation of this study is its observational nature.CONCLUSIONS: In our study, ERG positivity at diagnosis can be used to estimate the risk of progression during AS. If confirmed, ERG status can be used to individualise AS programmes.PATIENT SUMMARY: The tissue biomarker ERG identifies active surveillance patients with an increased risk of disease progression.

AB - BACKGROUND: Compelling biomarkers identifying prostate cancer patients with a high risk of progression during active surveillance (AS) are needed.OBJECTIVE: To examine the association between ERG expression at diagnosis and the risk of progression during AS.DESIGN, SETTING, AND PARTICIPANTS: This study included 265 patients followed on AS with prostate-specific antigen (PSA) measurements, clinical examinations, and 10-12 core rebiopsies from 2002 to 2012 in a prospectively maintained database. ERG immunohistochemical staining was performed on diagnostic paraffin-embedded formalin-fixed sections with a ready-to-use kit (anti-ERG, EPR3864). Men were characterised as ERG positive if a minimum of one tumour focus demonstrated ERG expression.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall AS progression was defined as clinical progression: increased clinical tumour category ≥cT2b by digital rectal examination and ultrasound, and/or histopathologic progression: upgrade of Gleason score, more than three positive cores or bilateral positive cores, and/or PSA progression: PSA doubling time <3 yr. Risk of progression was analysed using multiple cause-specific Cox regression and stratified cumulative incidences (Aalen-Johansen method). Curatively intended treatment, watchful waiting, and death without progression were treated as competing events.RESULTS AND LIMITATIONS: A total of 121 of 142 ERG-negative and 96 of 123 ERG-positive patients had complete diagnostic information. In competing risk models, the ERG-positive group showed significantly higher incidences of overall AS progression (p<0.0001) and of the subgroups PSA progression (p<0.0001) and histopathologic progression (p<0.0001). The 2-yr cumulative incidence of overall AS progression was 21.7% (95% confidence interval [CI], 14.3-29.1) in the ERG-negative group compared with 58.6% (95% CI, 48.7-68.5) in the ERG-positive group. ERG positivity was a significant predictor of overall AS progression in multiple Cox regression (hazard ratio: 2.45; 95% CI, 1.62-3.72; p<0.0001). The main limitation of this study is its observational nature.CONCLUSIONS: In our study, ERG positivity at diagnosis can be used to estimate the risk of progression during AS. If confirmed, ERG status can be used to individualise AS programmes.PATIENT SUMMARY: The tissue biomarker ERG identifies active surveillance patients with an increased risk of disease progression.

U2 - 10.1016/j.eururo.2014.02.058

DO - 10.1016/j.eururo.2014.02.058

M3 - Journal article

C2 - 24630684

VL - 66

SP - 851

EP - 860

JO - European Urology

JF - European Urology

SN - 0302-2838

IS - 5

ER -