title: Evaluation of urinary prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG score changes when starting androgen-deprivation therapy with triptorelin 6-month formulation in patients with locally advanced and metastatic prostate cancer.
abstract: OBJECTIVE
  To assess prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG scores in patients with advanced and metastatic prostate cancer at baseline and after 6 months of treatment with triptorelin 22.5 mg, and analyse these scores in patient-groups defined by different disease characteristics.
  
  
  METHODS
  The Triptocare study was a prospective, open-label, multicentre, single-arm, Phase III study of triptorelin 22.5 mg in men with locally advanced or metastatic prostate cancer, who were naïve to androgen-deprivation therapy (ADT). The primary objective was to model the urinary PCA3 change at 6 months, according to baseline variables. Other outcome measures included urinary PCA3 and TMPRSS2-ERG scores and statuses, and serum testosterone and prostate-specific antigen (PSA) levels at baseline and at 1, 3 and 6 months after initiation of ADT. Safety was assessed by recording adverse events and changes in laboratory parameters.
  
  
  RESULTS
  The intent-to-treat population comprised 322 patients; 39 (12.1%) had non-assessable PCA3 scores at baseline, and 109/322 (33.9%), 215/313 (68.7%) and 232/298 (77.9%) had non-assessable PCA3 scores at 1, 3 and 6 months, respectively. Baseline Gleason score was the only variable associated with non-assessability of PCA3 score at 6 months (P = 0.017) - the hazard of having a non-assessable PCA3 score at 6 months was 1.824-fold higher (95% confidence interval 1.186-2.805) in patients with a Gleason score ≥8 vs those with a Gleason score ≤6. The median PCA3 scores at baseline were significantly higher in patients aged ≥65 years vs those aged <65 years and in patients with a serum PSA level <100 ng/mL vs those with serum PSA level of >200 ng/mL. The median PCA3 score was significantly lower in patients with metastasis than in patients with no metastasis or unknown metastasis status. TMPRSS2-ERG scores ≥35 were considered positive (n = 149 [51.6%]). Age, presence of metastasis, PSA level and Gleason score at baseline were not associated with a significant difference in the proportion of TMPRSS2-ERG-positive scores. The median serum PSA levels decreased from 45.5 ng/mL at baseline to 1.2 ng/mL after 6 months, and as expected, >90% of patients achieved castrate levels of testosterone (<50 ng/dL) at 1, 3, and 6 months during triptorelin treatment. The safety profile reported from this study is consistent with the known safety profile of triptorelin.
  
  
  CONCLUSIONS
  These data from the Triptocare study suggest that urinary PCA3 or TMPRSS2-ERG score are not reliable markers of cancer stage in advanced prostate cancer. Urinary PCA3 and TMPRSS2-ERG scores do not appear to be useful in assessing response to ADT in advanced prostate cancer, with most patients having non-assessable scores after 6 months of treatment.
authors.affiliation: Urology Unit, Infanta Sofía University Hospital, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Piñeiro
authors.forename: Jack A
authors.initials: JA
authors.lastname: Schalken
authors.forename: Patrick
authors.initials: P
authors.lastname: Cabri
authors.forename: Pascal
authors.initials: P
authors.lastname: Maisonobe
authors.forename: Alexandre
authors.initials: A
authors.lastname: de la Taille
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000652:urine*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000652:urine*; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013739:Testosterone / Q000097:blood; D017329:Triptorelin Pamoate / Q000627:therapeutic use*
chemical_list: D000951:Antigens, Neoplasm; D018931:Antineoplastic Agents, Hormonal; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; C479341:prostate cancer antigen 3, human; D017329:Triptorelin Pamoate; D013739:Testosterone; D017430:Prostate-Specific Antigen
keywords: GnRH agonist; PCA3; TMPRSS2-ERG; advanced prostate cancer; disease severity