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Predictive Value of Four Kallikrein Markers for Pathologically Insignificant Compared With Aggressive Prostate Cancer in Radical Prostatectomy Specimens: Results From the European Randomized Study of Screening for Prostate Cancer Section Rotterdam

Carlsson, Sigrid; Maschino, Alexandra; Schroder, Fritz; Bangma, Chris; Steyerberg, Ewout W.; van der Kwast, Theo; van Leenders, Geert; Vickers, Andrew; Lilja, Hans LU and Roobol, Monique J. (2013) In European Urology 64(5). p.693-699
Abstract
Background: Treatment decisions can be difficult in men with low-risk prostate cancer (PCa). Objective: To evaluate the ability of a panel of four kallikrein markers in blood-total prostate-specific antigen (PSA), free PSA, intact PSA, and kallikrein-related peptidase 2-to distinguish between pathologically insignificant and aggressive disease on pathologic examination of radical prostatectomy (RP) specimens as well as to calculate the number of avoidable surgeries. Design, setting, and participants: The cohort comprised 392 screened men participating in rounds 1 and 2 of the Rotterdam arm of the European Randomized Study of Screening for Prostate Cancer. Patients were diagnosed with PCa because of an elevated PSA >= 3.0 ng/ml and were... (More)
Background: Treatment decisions can be difficult in men with low-risk prostate cancer (PCa). Objective: To evaluate the ability of a panel of four kallikrein markers in blood-total prostate-specific antigen (PSA), free PSA, intact PSA, and kallikrein-related peptidase 2-to distinguish between pathologically insignificant and aggressive disease on pathologic examination of radical prostatectomy (RP) specimens as well as to calculate the number of avoidable surgeries. Design, setting, and participants: The cohort comprised 392 screened men participating in rounds 1 and 2 of the Rotterdam arm of the European Randomized Study of Screening for Prostate Cancer. Patients were diagnosed with PCa because of an elevated PSA >= 3.0 ng/ml and were treated with RP between 1994 and 2004. Outcome measurements and statistical analysis: We calculated the accuracy (area under the curve [AUC]) of statistical models to predict pathologically aggressive PCa (pT3-T4, extracapsular extension, tumor volume >0.5 cm(3), or any Gleason grade >= 4) based on clinical predictors (age, stage, PSA, biopsy findings) with and without levels of four kallikrein markers in blood. Results and limitations: A total of 261 patients (67%) had significant disease on pathologic evaluation of the RP specimen. While the clinical model had good accuracy in predicting aggressive disease, reflected in a corrected AUC of 0.81, the four kallikrein markers enhanced the base model, with an AUC of 0.84 (p < 0.0005). The model retained its ability in patients with low-risk and very-low-risk disease and in comparison with the Steyerberg nomogram, a published prediction model. Clinical application of the model incorporating the kallikrein markers would reduce rates of surgery by 135 of 1000 patients overall and 110 of 334 patients with pathologically insignificant disease. A limitation of the present study is that clinicians may be hesitant to make recommendations against active treatment on the basis of a statistical model. Conclusions: Our study provided proof of principle that predictions based on levels of four kallikrein markers in blood distinguish between pathologically insignificant and aggressive disease after RP with good accuracy. In the future, clinical use of the model could potentially reduce rates of immediate unnecessary active treatment. (c) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Prostate-specific antigen/blood, Prostatic neoplasms, Mass screening, Radical prostatectomy, Kallikrein-related peptidases
in
European Urology
volume
64
issue
5
pages
693 - 699
publisher
Elsevier
external identifiers
  • wos:000325478100006
  • scopus:84885434644
ISSN
1873-7560
DOI
10.1016/j.eururo.2013.04.040
language
English
LU publication?
yes
id
77e18bb8-492e-453d-8c01-4bde6e7fe655 (old id 4160286)
date added to LUP
2013-12-06 12:23:15
date last changed
2019-05-26 04:04:03
@article{77e18bb8-492e-453d-8c01-4bde6e7fe655,
  abstract     = {Background: Treatment decisions can be difficult in men with low-risk prostate cancer (PCa). Objective: To evaluate the ability of a panel of four kallikrein markers in blood-total prostate-specific antigen (PSA), free PSA, intact PSA, and kallikrein-related peptidase 2-to distinguish between pathologically insignificant and aggressive disease on pathologic examination of radical prostatectomy (RP) specimens as well as to calculate the number of avoidable surgeries. Design, setting, and participants: The cohort comprised 392 screened men participating in rounds 1 and 2 of the Rotterdam arm of the European Randomized Study of Screening for Prostate Cancer. Patients were diagnosed with PCa because of an elevated PSA &gt;= 3.0 ng/ml and were treated with RP between 1994 and 2004. Outcome measurements and statistical analysis: We calculated the accuracy (area under the curve [AUC]) of statistical models to predict pathologically aggressive PCa (pT3-T4, extracapsular extension, tumor volume &gt;0.5 cm(3), or any Gleason grade &gt;= 4) based on clinical predictors (age, stage, PSA, biopsy findings) with and without levels of four kallikrein markers in blood. Results and limitations: A total of 261 patients (67%) had significant disease on pathologic evaluation of the RP specimen. While the clinical model had good accuracy in predicting aggressive disease, reflected in a corrected AUC of 0.81, the four kallikrein markers enhanced the base model, with an AUC of 0.84 (p &lt; 0.0005). The model retained its ability in patients with low-risk and very-low-risk disease and in comparison with the Steyerberg nomogram, a published prediction model. Clinical application of the model incorporating the kallikrein markers would reduce rates of surgery by 135 of 1000 patients overall and 110 of 334 patients with pathologically insignificant disease. A limitation of the present study is that clinicians may be hesitant to make recommendations against active treatment on the basis of a statistical model. Conclusions: Our study provided proof of principle that predictions based on levels of four kallikrein markers in blood distinguish between pathologically insignificant and aggressive disease after RP with good accuracy. In the future, clinical use of the model could potentially reduce rates of immediate unnecessary active treatment. (c) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.},
  author       = {Carlsson, Sigrid and Maschino, Alexandra and Schroder, Fritz and Bangma, Chris and Steyerberg, Ewout W. and van der Kwast, Theo and van Leenders, Geert and Vickers, Andrew and Lilja, Hans and Roobol, Monique J.},
  issn         = {1873-7560},
  keyword      = {Prostate-specific antigen/blood,Prostatic neoplasms,Mass screening,Radical prostatectomy,Kallikrein-related peptidases},
  language     = {eng},
  number       = {5},
  pages        = {693--699},
  publisher    = {Elsevier},
  series       = {European Urology},
  title        = {Predictive Value of Four Kallikrein Markers for Pathologically Insignificant Compared With Aggressive Prostate Cancer in Radical Prostatectomy Specimens: Results From the European Randomized Study of Screening for Prostate Cancer Section Rotterdam},
  url          = {http://dx.doi.org/10.1016/j.eururo.2013.04.040},
  volume       = {64},
  year         = {2013},
}