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

Steuber, Thomas; Vickers, Andrew; Haese, Alexander; Kattan, Michael W.; Eastham, James A.; Scardino, Peter T.; Huland, Hartwig and Lilja, Hans LU (2007) In International Journal of Cancer 120(7). p.1499-1504
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 pretreatment serum from 355 men referred for prostate biopsy. Age and total PSA were combined in a "base" regression model to predict biopsy outcome. We then compared this... (More)
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 pretreatment serum from 355 men referred for prostate biopsy. Age and total PSA were combined in a "base" regression model to predict 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. (c) 2007 Wiley-Liss, Inc. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
human glandular, kallikrein 2, circulating biomarkers, multivariable models, nicked PSA, prostate cancer diagnosis, prostate-specific antigen
in
International Journal of Cancer
volume
120
issue
7
pages
1499 - 1504
publisher
John Wiley & Sons
external identifiers
  • wos:000244610700016
  • scopus:33847617415
ISSN
0020-7136
DOI
10.1002/ijc.22427
language
English
LU publication?
yes
id
7e30f2eb-69dc-4a88-89a7-d8beb51b20a7 (old id 672681)
date added to LUP
2007-12-20 12:10:57
date last changed
2017-10-08 03:29:21
@article{7e30f2eb-69dc-4a88-89a7-d8beb51b20a7,
  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 pretreatment serum from 355 men referred for prostate biopsy. Age and total PSA were combined in a "base" regression model to predict 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. (c) 2007 Wiley-Liss, Inc.},
  author       = {Steuber, Thomas and Vickers, Andrew and Haese, Alexander and Kattan, Michael W. and Eastham, James A. and Scardino, Peter T. and Huland, Hartwig and Lilja, Hans},
  issn         = {0020-7136},
  keyword      = {human glandular,kallikrein 2,circulating biomarkers,multivariable models,nicked PSA,prostate cancer diagnosis,prostate-specific antigen},
  language     = {eng},
  number       = {7},
  pages        = {1499--1504},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Free PSA isoforms and intact and cleaved forms of urokinase plasminogen activator receptor in serum improve selection of patients for prostate cancer biopsy},
  url          = {http://dx.doi.org/10.1002/ijc.22427},
  volume       = {120},
  year         = {2007},
}