Prognostic and predictive value of intact and cleaved forms of the urokinase plasminogen activator receptor in metastatic prostate cancer

• Published in: The Prostate Vol. 71; no. 8; pp. 899 - 907
• Main Authors: Almasi, Charlotte E., Brasso, Klaus, Iversen, Peter, Pappot, Helle, Høyer-Hansen, Gunilla, Danø, Keld, Christensen, Ib J.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.06.2011; Wiley-Liss
• Subjects: Aged; Aged, 80 and over; Androgen Antagonists - therapeutic use; Biological and medical sciences; Bone Neoplasms - blood; Bone Neoplasms - diagnostic imaging; Bone Neoplasms - mortality; Bone Neoplasms - secondary; Carcinoma - blood; Carcinoma - mortality; Carcinoma - secondary; Estradiol - analogs & derivatives; Estradiol - therapeutic use; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; prediction; Prognosis; prostate cancer; Prostatic Neoplasms - blood; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; Radiography; Randomized Controlled Trials as Topic; Receptors, Urokinase Plasminogen Activator - blood; Retrospective Studies; time-resolved fluorescence immunoassays; Treatment Outcome; Tumors; Tumors of the urinary system; uPAR; Urinary tract. Prostate gland; Andrology; Nephrology; u-Plasminogen activator; Prognosis; Prostate disease; Fluorescence; Metastasis; time-resolved fluorescence immunoassays; Immunological method; Predictive value; Advanced stage; uPAR; Male genital diseases; Biological receptor; Urinary system disease; Serine endopeptidases; Enzyme; Gynecology; Prediction; Malignant tumor; Peptidases; Time resolution; Hydrolases; Metastatic; Predictive factor; Prostate cancer; Cancer
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.21306

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. PATIENTS AND 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). CONCLUSION 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. Prostate 71:899–907, 2011. © 2010 Wiley‐Liss, Inc.