Articles

Prostate Cancer

Prostate Cancer Gene 3 (PCA3): Development and Internal Validation of a Novel Biopsy Nomogram

By: Felix K. Chuna 1 lowast , Alexandre de la Taillec, Hendrik van Poppeld, Michael Marbergere, Arnulf Stenzlf, Peter F.A. Muldersg, Hartwig Hulandb, Clement-Claude Abbouc, Alexander B. Stillebroerg, Martijn P.M.Q. van Gilsg, Jack A. Schalkeng, Yves Fradeth, Leonard S. Marksi, William Ellisj, Alan W. Partink and Alexander Haeseb 1 lowastlowast

European Urology, Volume 56 Issue 1, October 2009, Pages 659-668

Published online: 01 October 2009

Keywords: Prostate biopsy, Prostate cancer gene 3, Biomarker, Prostate cancer, Nomogram, Risk assessment

Abstract Full Text Full Text PDF (1,3 MB)

Abstract

Background

Urinary prostate cancer gene 3 (PCA3) represents a promising novel marker of prostate cancer detection.

Objective

To test whether urinary PCA3 assay improves prostate cancer (PCa) risk assessment and to construct a decision-making aid in a multi-institutional cohort with pre–prostate biopsy data.

Design, setting, and participants

PCA3 assay cut-off threshold analyses were followed by logistic regression models which used established predictors to assess PCa-risk at biopsy in a large multi-institutional data set of 809 men at risk of harboring PCa.

Measurements

Regression coefficients were used to construct four sets of nomograms. Predictive accuracy (PA) estimates of biopsy outcome predictions were quantified using the area under the curve of the receiver operator characteristic analysis in models with and without PCA3. Bootstrap resamples were used for internal validation and to reduce overfit bias. The extent of overestimation or underestimation of the observed PCa rate at biopsy was explored graphically using nonparametric loss-calibration plots. Differences in PA were tested using the Mantel-Haenszel test. Finally, nomogram-derived probability cut-offs were tested to assess the ability to identify patients with or without PCa.

Results and limitations

PCA3 was identified as a statistically independent risk factor of PCa at biopsy. Addition of a PCA3 assay improved bootstrap-corrected multivariate PA of the base model between 2% and 5%. The highest increment in PA resulted from a PCA3 assay cut-off threshold of 17, where a 5% gain in PA (from 0.68 to 0.73, p=0.04) was recorded. Nomogram probability–derived risk cut-off analyses further corroborate the superiority of the PCA3 nomogram over the base model.

Conclusions

PCA3 fulfills the criteria for a novel marker capable of increasing PA of multivariate biopsy models. This novel PCA3-based nomogram better identifies men at risk of harboring PCa and assists in deciding whether further evaluation is necessary.

Take Home Message

Prostate cancer gene 3 (PCA3) represents a novel marker that is capable of increasing the accuracy of multivariable biopsy models. We suggest the use of our PCA3-based nomogram, which better identifies people at risk of harboring prostate cancer, to assist clinicians in deciding whether further evaluation is necessary.

Keywords: Prostate biopsy, Prostate cancer gene 3, Biomarker, Prostate cancer, Nomogram, Risk assessment.

Footnotes

a Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany

b Martini Clinic, Prostate Cancer Center, University Hospital Eppendorf, Hamburg, Germany

c Hopital Henri Mondor, Créteil, France

d Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium

e University of Vienna, Vienna, Austria

f Uniklinikum Tübingen, Tübingen, Germany

g Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

h Department of Urology, Universite Laval, Quebec City, Quebec, Canada

i Urological Sciences Research Foundation, Culver City, CA, USA

j University of Washington Medical Center, Seattle, WA, USA

k Department of Urology, Johns Hopkins University Medical Institution, Baltimore, MD, USA

lowast Corresponding author. Department of Urology, University Hospital Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

lowastlowast Co-corresponding author. Martini Clinic, Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

1 Both authors contributed equally to the manuscript.

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