The predictive value of ERG protein expression for development of castration-resistant prostate cancer in hormone-naïve advanced prostate cancer treated with primary androgen deprivation therapy

TY - JOUR

T1 - The predictive value of ERG protein expression for development of castration-resistant prostate cancer in hormone-naïve advanced prostate cancer treated with primary androgen deprivation therapy

AU - Berg, Kasper Drimer

AU - Røder, Martin A

AU - Thomsen, Frederik B

AU - Vainer, Ben

AU - Gerds, Thomas A

AU - Brasso, Klaus

AU - Iversen, Peter

N1 - © 2015 Wiley Periodicals, Inc.

PY - 2015/10/1

Y1 - 2015/10/1

N2 - Background Biomarkers predicting response to primary androgen deprivation therapy (ADT) and risk of castration-resistant prostate cancer (CRPC) is lacking. We aimed to analyse the predictive value of ERG expression for development of CRPC. Methods In total, 194 patients with advanced and/or metastatic prostate cancer (PCa) treated with first-line castration-based ADT were included. ERG protein expression was analysed in diagnostic specimens using immunohistochemistry (anti-ERG, EPR3864). Time to CRPC was compared between ERG subgroups using multiple cause-specific Cox regression stratified on ERG-status. Risk reclassification and time-dependent area under the ROC curves were used to assess the discriminative ability of ERG-status. Time to PSA-nadir, proportion achieving PSA-nadir ≤0.2ng/ml, and risk of PCa-specific death were secondary endpoints. Results Median follow-up was 6.8 years (IQR: 4.9-7.3). In total, 105 patients (54.1%) were ERG-positive and 89 (45.9%) were ERG-negative. No difference in risk of CRPC was observed between ERG subgroups (P=0.51). Median time to CRPC was 3.9 years (95%CI: 3.2-5.1) and 4.5 years (95%CI: 2.3-not reached) in the ERG-positive and ERG-negative group, respectively. Compared to a model omitting ERG-status, the ERG-stratified model showed comparable AUC values 1 year (77.6% vs. 78.0%, P=0.82), 2 years (71.7% vs. 71.8%, P=0.85), 5 years (68.5% vs. 69.9%, P=0.32), and 8 years (67.9% vs. 71.4%, P=0.21) from ADT initiation. No differences in secondary endpoints were observed. Conclusions ERG expression was not associated with risk of CRPC suggesting that ERG is not a candidate biomarker for predicting response to primary ADT in patients diagnosed with advanced and/or metastatic PCa. Prostate 75:1499-1509, 2015.

AB - Background Biomarkers predicting response to primary androgen deprivation therapy (ADT) and risk of castration-resistant prostate cancer (CRPC) is lacking. We aimed to analyse the predictive value of ERG expression for development of CRPC. Methods In total, 194 patients with advanced and/or metastatic prostate cancer (PCa) treated with first-line castration-based ADT were included. ERG protein expression was analysed in diagnostic specimens using immunohistochemistry (anti-ERG, EPR3864). Time to CRPC was compared between ERG subgroups using multiple cause-specific Cox regression stratified on ERG-status. Risk reclassification and time-dependent area under the ROC curves were used to assess the discriminative ability of ERG-status. Time to PSA-nadir, proportion achieving PSA-nadir ≤0.2ng/ml, and risk of PCa-specific death were secondary endpoints. Results Median follow-up was 6.8 years (IQR: 4.9-7.3). In total, 105 patients (54.1%) were ERG-positive and 89 (45.9%) were ERG-negative. No difference in risk of CRPC was observed between ERG subgroups (P=0.51). Median time to CRPC was 3.9 years (95%CI: 3.2-5.1) and 4.5 years (95%CI: 2.3-not reached) in the ERG-positive and ERG-negative group, respectively. Compared to a model omitting ERG-status, the ERG-stratified model showed comparable AUC values 1 year (77.6% vs. 78.0%, P=0.82), 2 years (71.7% vs. 71.8%, P=0.85), 5 years (68.5% vs. 69.9%, P=0.32), and 8 years (67.9% vs. 71.4%, P=0.21) from ADT initiation. No differences in secondary endpoints were observed. Conclusions ERG expression was not associated with risk of CRPC suggesting that ERG is not a candidate biomarker for predicting response to primary ADT in patients diagnosed with advanced and/or metastatic PCa. Prostate 75:1499-1509, 2015.

U2 - 10.1002/pros.23026

DO - 10.1002/pros.23026

M3 - Journal article

C2 - 26053696

SN - 0270-4137

VL - 75

SP - 1499

EP - 1509

JO - The Prostate

JF - The Prostate

IS - 14

ER -