Initial prostate biopsy: Development and internal validation of a biopsy-specific nomogram based on the prostate cancer antigen 3 assay

Jens Hansen, Marco Auprich, Sascha A. Ahyai, Alexandre De La Taille, Hendrik Van Poppel, Michael Marberger, Arnulf Stenzl, Peter F A Mulders, Hartwig Huland, Margit Fisch, Clement Claude Abbou, Jack A. Schalken, Yves Fradet, Leonard S. Marks, William Ellis, Alan W. Partin, Karl Pummer, Markus Graefen, Alexander Haese, Jochen WalzAlberto Briganti, Shahrokh F. Shariat, Felix K. Chun

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)201-209
Number of pages9
JournalEuropean Urology
Volume63
Issue number2
DOIs
Publication statusPublished - Feb 2013

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Nomograms
Prostate
Prostatic Neoplasms
Biopsy
Antigens
Prostate-Specific Antigen

Keywords

  • Biomarker
  • Decision curve analysis
  • Initial prostate biopsy
  • Internal validation
  • Nomogram
  • Prostate cancer
  • Prostate cancer antigen 3

ASJC Scopus subject areas

  • Urology

Cite this

Hansen, J., Auprich, M., Ahyai, S. A., De La Taille, A., Van Poppel, H., Marberger, M., ... Chun, F. K. (2013). Initial prostate biopsy: Development and internal validation of a biopsy-specific nomogram based on the prostate cancer antigen 3 assay. European Urology, 63(2), 201-209. https://doi.org/10.1016/j.eururo.2012.07.030

Initial prostate biopsy : Development and internal validation of a biopsy-specific nomogram based on the prostate cancer antigen 3 assay. / Hansen, Jens; Auprich, Marco; Ahyai, Sascha A.; De La Taille, Alexandre; Van Poppel, Hendrik; Marberger, Michael; Stenzl, Arnulf; Mulders, Peter F A; Huland, Hartwig; Fisch, Margit; Abbou, Clement Claude; Schalken, Jack A.; Fradet, Yves; Marks, Leonard S.; Ellis, William; Partin, Alan W.; Pummer, Karl; Graefen, Markus; Haese, Alexander; Walz, Jochen; Briganti, Alberto; Shariat, Shahrokh F.; Chun, Felix K.

In: European Urology, Vol. 63, No. 2, 02.2013, p. 201-209.

Research output: Contribution to journalArticle

Hansen, J, Auprich, M, Ahyai, SA, De La Taille, A, Van Poppel, H, Marberger, M, Stenzl, A, Mulders, PFA, 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 2013, 'Initial prostate biopsy: Development and internal validation of a biopsy-specific nomogram based on the prostate cancer antigen 3 assay', European Urology, vol. 63, no. 2, pp. 201-209. https://doi.org/10.1016/j.eururo.2012.07.030
Hansen, Jens ; Auprich, Marco ; Ahyai, Sascha A. ; De La Taille, Alexandre ; Van Poppel, Hendrik ; Marberger, Michael ; Stenzl, Arnulf ; Mulders, Peter F A ; Huland, Hartwig ; Fisch, Margit ; Abbou, Clement Claude ; Schalken, Jack A. ; Fradet, Yves ; Marks, Leonard S. ; Ellis, William ; Partin, Alan W. ; Pummer, Karl ; Graefen, Markus ; Haese, Alexander ; Walz, Jochen ; Briganti, Alberto ; Shariat, Shahrokh F. ; Chun, Felix K. / Initial prostate biopsy : Development and internal validation of a biopsy-specific nomogram based on the prostate cancer antigen 3 assay. In: European Urology. 2013 ; Vol. 63, No. 2. pp. 201-209.
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abstract = "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.",
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T1 - Initial prostate biopsy

T2 - Development and internal validation of a biopsy-specific nomogram based on the prostate cancer antigen 3 assay

AU - Hansen, Jens

AU - Auprich, Marco

AU - Ahyai, Sascha A.

AU - De La Taille, Alexandre

AU - Van Poppel, Hendrik

AU - Marberger, Michael

AU - Stenzl, Arnulf

AU - Mulders, Peter F A

AU - Huland, Hartwig

AU - Fisch, Margit

AU - Abbou, Clement Claude

AU - Schalken, Jack A.

AU - Fradet, Yves

AU - Marks, Leonard S.

AU - Ellis, William

AU - Partin, Alan W.

AU - Pummer, Karl

AU - Graefen, Markus

AU - Haese, Alexander

AU - Walz, Jochen

AU - Briganti, Alberto

AU - Shariat, Shahrokh F.

AU - Chun, Felix K.

PY - 2013/2

Y1 - 2013/2

N2 - 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.

AB - 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.

KW - Biomarker

KW - Decision curve analysis

KW - Initial prostate biopsy

KW - Internal validation

KW - Nomogram

KW - Prostate cancer

KW - Prostate cancer antigen 3

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