Free PSA isoforms and intact and cleaved forms of urokinase plasminogen activator receptor in serum improve selection of patients for prostate cancer biopsy Journal Article

  

Authors:	Steuber, T.; Vickers, A.; Haese, A.; Kattan, M. W.; Eastham, J. A.; Scardino, P. T.; Huland, H.; Lilja, H.
Article Title:	Free PSA isoforms and intact and cleaved forms of urokinase plasminogen activator receptor in serum improve selection of patients for prostate cancer biopsy
Abstract:	Clinicians currently use simple cut-points, such as serum prostate-specific antigen (PSA) ≥4 ng/ml, to decide whether to recommend further work-up for prostate cancer (PCa). As an alternative strategy, we evaluated multivariable models giving probabilities of a PCa diagnosis based on PSA and several circulating novel biomarkers. We measured total PSA, free PSA (fPSA), fPSA subfractions (single-chain fPSA-I and multichain fPSA-N), total human glandular kallikrein 2 (hK2) and full-length and cleaved forms of soluble urokinase plasminogen activator receptor (suPAR) in pro-treatment serum from 355 men referred for prostate biopsy. Age and total PSA were combined in a "base" regression model to pre-dict biopsy outcome. We then compared this base model to models supplemented by various combinations of circulating markers, using concordance index (AUC) to measure diagnostic discrimination. PCa prediction was significantly enhanced by models supplemented by measurements of suPAR fragments and fPSA isoforms. Addition of these markers improved bootstrap-corrected AUC from 0.611 for a cut-point and 0.706 for the base model to 0.754 for the full model (p = 0.005). This improved diagnostic accuracy was also seen in subanalysis of patients with PSA 2-9.99 ng/ml and normal findings on DRE (0.652 vs. 0.715, p = 0.039). In this setting, hK2 did not add diagnostic information. Measurements of individual forms of suPAR and PSA isoforms contributed significantly to discrimination of men with PCa from those with no evidence of malignancy. © 2007 Wiley-Liss, Inc.
Keywords:	adult; controlled study; aged; middle aged; major clinical study; patient selection; cancer staging; cancer diagnosis; neoplasm staging; biological marker; prostate specific antigen; tumor markers, biological; tumor marker; biopsy; prostate cancer; gleason score; prostate-specific antigen; prostatic neoplasms; blood sampling; prostate biopsy; area under curve; multivariate analysis; statistical model; serum; receptors, cell surface; urokinase receptor; tissue kallikreins; nicked psa; circulating biomarkers; human glandular kallikrein 2; multivariable models; prostate cancer diagnosis
Journal Title:	International Journal of Cancer
Volume:	120
Issue:	7
ISSN:	0020-7136
Publisher:	John Wiley & Sons
Date Published:	2007-04-01
Start Page:	1499
End Page:	1504
Language:	English
DOI:	10.1002/ijc.22427
PUBMED:	17205511
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-33847617415&partnerID=40&md5=6e448e0defa76347592b4dfb21035eff
Notes:	--- - "Cited By (since 1996): 24" - "Export Date: 17 November 2011" - "CODEN: IJCNA" - "Source: Scopus"

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