title: 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.
abstract: 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 ≤0.2 ng/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.
authors.affiliation: Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kasper D
authors.initials: KD
authors.lastname: Berg
authors.affiliation: Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Røder
authors.affiliation: Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Frederik B
authors.initials: FB
authors.lastname: Thomsen
authors.affiliation: Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ben
authors.initials: B
authors.lastname: Vainer
authors.affiliation: Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Gerds
authors.affiliation: Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Brasso
authors.affiliation: Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Iversen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood* / Q000175:diagnosis*; D012189:Retrospective Studies; D015534:Trans-Activators / Q000096:biosynthesis*; D000071230:Transcriptional Regulator ERG; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D014408:Biomarkers, Tumor; C072312:ERG protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D007987:Gonadotropin-Releasing Hormone
keywords: ERG expression; TMPRSS2-ERG; androgen deprivation therapy; castration-resistant prostate cancer; endocrine therapy; predictive biomarker; prostate cancer