title: Prognostic and predictive value of intact and cleaved forms of the urokinase plasminogen activator receptor in metastatic prostate cancer.
abstract: BACKGROUND
  The purpose of this study was to investigate the prognostic value of different forms of the urokinase receptor, uPAR, in serum from prostate cancer (PC) patients.
  
  
  METHODS
  The uPAR forms were measured in samples from 131 metastatic PC patients. These constituted a subset of patients included in a randomized clinical trial of treatment with total androgen blockade (TAB) versus polyestradiol phosphate (PEP). Pre-treatment serum levels of intact uPAR (uPAR(I-III)), intact plus cleaved uPAR (uPAR(I-III) + uPAR(II-III)) and domain I (uPAR(I)) were measured using time-resolved fluorescence immunoassays (TR-FIAs).
  
  
  RESULTS
  High serum levels of each of the uPAR forms were significantly associated with short overall survival (OS). The prognostic impact was strongest in the TAB treated patients with all uPAR forms being statistically significant. In multivariate analysis, uPAR(I-III) + uPAR(II-III) was an independent prognostic factor in TAB treated patients (HR = 5.2, 95% confidence interval (CI): 2.5-10.6, P < 0.0001) but not in PEP treated patients (P = 0.40). In the entire study population, OS was similar in the two treatment groups. The survival analysis showed significant interactions between treatment modality and the level of either uPAR(I-III) or uPAR(I-III) + uPAR(II-III). High levels of uPAR(I-III) + uPAR(II-III) were found to be predictive of effect of PEP versus TAB treatment. Patients with uPAR(I-III) + uPAR(II-III) levels above the median had significantly longer OS (median difference 11.3 months), if treated with PEP rather than with TAB (HR = 1.8, 95% CI:1.1-3.1, P = 0.03).
  
  
  CONCLUSIONS
  uPAR forms are significantly associated with OS. High uPAR(I-III) + uPAR(II-III) predicts longer OS in patients treated with PEP compared to TAB. uPAR forms are promising prognostic and predictive markers in PC.
authors: The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark. c_elberling@hotmail.com
authors: Charlotte E
authors: CE
authors: Almasi
authors: Klaus
authors: K
authors: Brasso
authors: Peter
authors: P
authors: Iversen
authors: Helle
authors: H
authors: Pappot
authors: Gunilla
authors: G
authors: Høyer-Hansen
authors: Keld
authors: K
authors: Danø
authors: Ib J
authors: IJ
authors: Christensen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000097:blood* / Q000000981:diagnostic imaging / Q000401:mortality / Q000556:secondary; D002277:Carcinoma / Q000097:blood* / Q000401:mortality / Q000556:secondary; D004958:Estradiol / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology; D011859:Radiography; D016032:Randomized Controlled Trials as Topic; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D055293:Receptors, Urokinase Plasminogen Activator; D004958:Estradiol; C008958:polyestradiol phosphate