BACKGROUND:Urinary prostate cancer antigen 3 (PCA3) assay in combination with established clinical risk factors improves the identification of men at risk of harboring prostate cancer (PCa) at initial biopsy (IBX).
OBJECTIVE:To develop and validate internally the first IBX-specific PCA3-based nomogram that allows an individual assessment of a man's risk of harboring any PCa and high-grade PCa (HGPCa).
DESIGN, SETTING, AND PARTICIPANTS:Clinical and biopsy data including urinary PCA3 score of 692 referred IBX men at risk of PCa were collected within two prospective multi-institutional studies.
INTERVENTION:IBX (≥10 biopsy cores) with standard risk factor assessment including prebiopsy urinary PCA3 measurement.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:PCA3 assay cut-off thresholds were investigated. Regression coefficients of logistic risk factor analyses were used to construct specific sets of PCA3-based nomograms to predict any PCa and HGPCa at IBX. Accuracy estimates for the presence of any PCa and HGPCa were quantified using area under the curve of the receiver operator characteristic analysis and compared with a clinical model. Bootstrap resamples were used for internal validation. Decision curve analyses quantified the clinical net benefit related to the novel PCA3-based IBX nomogram versus the clinical model.
RESULTS AND LIMITATIONS:Any PCa and HGPCa were diagnosed in 46% (n=318) and 20% (n=137), respectively. Age, prostate-specific antigen, digital rectal examination, prostate volume, and PCA3 were independent predictors of PCa at IBX (all p< 0.001). The PCA3-based IBX nomograms significantly outperformed the clinical models without PCA3 (all p< 0.001). Accuracy was increased by 4.5-7.1% related to PCA3 inclusion. When applying nomogram-derived PCa probability thresholds ≤ 30%, only a few patients with HGPCa (≤ 2%) will be missed while avoiding up to 55% of unnecessary biopsies. External validation of the PCA3-based IBX-specific nomogram is warranted.
CONCLUSIONS: The internally validated PCA3-based IBX-specific nomogram outperforms a clinical prediction model without PCA3 for the prediction of any PCa, leading to the avoidance of unnecessary biopsies while missing only a few cases of HGPCa. Our findings support the concepts of a combination of novel markers with established clinical risk factors and the superiority of decision tools that are specific to a clinical scenario.
Written by:
Hansen J, Auprich M, Ahyai SA, de la Taille A, van Poppel H, Marberger M, Stenzl A, Mulders PF, Huland H, Fisch M, Abbou CC, Schalken JA, Fradet Y, Marks LS, Ellis W, Partin AW, Pummer K, Graefen M, Haese A, Walz J, Briganti A, Shariat SF, Chun FK. Are you the author?
Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Martini Clinic Prostate Cancer Center, University Hospital Eppendorf, Hamburg, Germany.
Reference: Eur Urol. 2012 Jul 20. Epub ahead of print.
doi: 10.1016/j.eururo.2012.07.030
PubMed Abstract
PMID: 22854248
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