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Association of the Circulating Levels of the Urokinase System of Plasminogen Activation With the Presence of Prostate Cancer and Invasion, Progression, and Metastasis

Shahrokh F. Shariat, Claus G. Roehrborn, John D. McConnell, Sangtae Park, Nina Alam, Thomas M. Wheeler, Kevin M. Slawin

From the Departments of Urology and Pathology, University of Texas Southwestern Medical Center, Dallas; and Baylor Prostate Center, Scott Department of Urology and Department of Pathology, Baylor College of Medicine, Houston, TX

Address reprint requests to Shahrokh F. Shariat, MD, Department of Urology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9110; e-mail: Shahrokh.Shariat{at}UTSouthwestern.edu

Purpose: To assess whether preoperative plasma levels of urokinase-type plasminogen activator (uPA) and its soluble receptor (uPAR) would predict cancer of the prostate (CaP) presence, stage, and prognosis.

Patients and Methods: Plasma levels of uPA and uPAR were measured in patients who underwent radical prostatectomy for clinically localized CaP (preoperative, n = 429; postoperative, n = 76), 44 healthy men, 19 patients with metastases to regional lymph nodes, and 10 patients with bone metastases.

Results: uPA and uPAR levels were significantly elevated in patients with CaP compared with healthy men and significantly declined after prostate removal. In CaP patients, uPA and uPAR levels both increased significantly from patients with nonmetastatic CaP to patients with lymph node metastases to patients with skeletal metastases. On univariate analysis, preoperative uPA and uPAR levels were significantly elevated in patients with extracapsular extension, seminal vesicle involvement, higher prostatectomy Gleason sum, lymph node invasion, lymphovascular invasion, perineural invasion, and higher tumor volume. Higher preoperative uPAR was associated with biochemical progression in univariate analysis. Conversely, higher preoperative uPA was independently associated with biochemical progression in preoperative or postoperative multivariate models. In patients with biochemical progression, preoperative uPA and uPAR were both significantly associated with shorter postprogression total serum prostate-specific antigen doubling times, failure to respond to salvage local radiation therapy, and/or development of distant metastasis.

Conclusion: Elevation of plasma uPA and uPAR levels in CaP patients seems to be partly caused by local release from the prostate. Plasma levels of uPA and uPAR are associated with features of biologically aggressive CaP, disease progression after radical prostatectomy, and metastasis.

Supported by the Austrian Program for Advanced Research and Technology.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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