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

TY - JOUR

T1 - Prognostic and predictive value of intact and cleaved forms of the urokinase plasminogen activator receptor in metastatic prostate cancer

AU - Almasi, Charlotte E

AU - Brasso, Klaus

AU - Iversen, Peter

AU - Pappot, Helle

AU - Høyer-Hansen, Gunilla

AU - Danø, Keld

AU - Christensen, Ib J

N1 - Copyright © 2010 Wiley-Liss, Inc.

PY - 2011/6/1

Y1 - 2011/6/1

N2 - 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 inTABtreated 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. 2011.

AB - 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 inTABtreated 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. 2011.

KW - Aged

KW - Aged, 80 and over

KW - Androgen Antagonists

KW - Bone Neoplasms

KW - Carcinoma

KW - Estradiol

KW - Humans

KW - Male

KW - Middle Aged

KW - Prognosis

KW - Prostatic Neoplasms

KW - Randomized Controlled Trials as Topic

KW - Receptors, Urokinase Plasminogen Activator

KW - Retrospective Studies

KW - Treatment Outcome

U2 - 10.1002/pros.21306

DO - 10.1002/pros.21306

M3 - Journal article

C2 - 21456072

SN - 0270-4137

VL - 71

SP - 899

EP - 907

JO - The Prostate. Supplement

JF - The Prostate. Supplement

IS - 8

ER -