Clinical validation of an epigenetic assay to predict negative histopathological results in repeat prostate biopsies

Alan Wayne Partin, Leander Van Neste, Eric A. Klein, Leonard S. Marks, Jason R. Gee, Dean A. Troyer, Kimberly Rieger-Christ, J. Stephen Jones, Cristina Magi-Galluzzi, Leslie A. Mangold, Bruce Trock, Raymond S. Lance, Joseph W. Bigley, Wim Van Criekinge, Jonathan Ira Epstein

Research output: Contribution to journalArticle

Abstract

Purpose The DOCUMENT multicenter trial in the United States validated the performance of an epigenetic test as an independent predictor of prostate cancer risk to guide decision making for repeat biopsy. Confirming an increased negative predictive value could help avoid unnecessary repeat biopsies. Materials and Methods We evaluated the archived, cancer negative prostate biopsy core tissue samples of 350 subjects from a total of 5 urological centers in the United States. All subjects underwent repeat biopsy within 24 months with a negative (controls) or positive (cases) histopathological result. Centralized blinded pathology evaluation of the 2 biopsy series was performed in all available subjects from each site. Biopsies were epigenetically profiled for GSTP1, APC and RASSF1 relative to the ACTB reference gene using quantitative methylation specific polymerase chain reaction. Predetermined analytical marker cutoffs were used to determine assay performance. Multivariate logistic regression was used to evaluate all risk factors. Results The epigenetic assay resulted in a negative predictive value of 88% (95% CI 85-91). In multivariate models correcting for age, prostate specific antigen, digital rectal examination, first biopsy histopathological characteristics and race the test proved to be the most significant independent predictor of patient outcome (OR 2.69, 95% CI 1.60-4.51). Conclusions The DOCUMENT study validated that the epigenetic assay was a significant, independent predictor of prostate cancer detection in a repeat biopsy collected an average of 13 months after an initial negative result. Due to its 88% negative predictive value adding this epigenetic assay to other known risk factors may help decrease unnecessary repeat prostate biopsies.

Original languageEnglish (US)
Pages (from-to)1081-1087
Number of pages7
JournalJournal of Urology
Volume192
Issue number4
DOIs
StatePublished - Oct 1 2014

Fingerprint

Epigenomics
Prostate
Biopsy
Prostatic Neoplasms
Digital Rectal Examination
Prostate-Specific Antigen
Methylation
Multicenter Studies
Decision Making
Logistic Models
Pathology
Polymerase Chain Reaction
Genes

Keywords

  • biopsy
  • epigenomics
  • methylation
  • prostate
  • prostatic neoplasms

ASJC Scopus subject areas

  • Urology
  • Medicine(all)

Cite this

Clinical validation of an epigenetic assay to predict negative histopathological results in repeat prostate biopsies. / Partin, Alan Wayne; Van Neste, Leander; Klein, Eric A.; Marks, Leonard S.; Gee, Jason R.; Troyer, Dean A.; Rieger-Christ, Kimberly; Jones, J. Stephen; Magi-Galluzzi, Cristina; Mangold, Leslie A.; Trock, Bruce; Lance, Raymond S.; Bigley, Joseph W.; Van Criekinge, Wim; Epstein, Jonathan Ira.

In: Journal of Urology, Vol. 192, No. 4, 01.10.2014, p. 1081-1087.

Research output: Contribution to journalArticle

Partin, AW, Van Neste, L, Klein, EA, Marks, LS, Gee, JR, Troyer, DA, Rieger-Christ, K, Jones, JS, Magi-Galluzzi, C, Mangold, LA, Trock, B, Lance, RS, Bigley, JW, Van Criekinge, W & Epstein, JI 2014, 'Clinical validation of an epigenetic assay to predict negative histopathological results in repeat prostate biopsies', Journal of Urology, vol. 192, no. 4, pp. 1081-1087. https://doi.org/10.1016/j.juro.2014.04.013
Partin, Alan Wayne ; Van Neste, Leander ; Klein, Eric A. ; Marks, Leonard S. ; Gee, Jason R. ; Troyer, Dean A. ; Rieger-Christ, Kimberly ; Jones, J. Stephen ; Magi-Galluzzi, Cristina ; Mangold, Leslie A. ; Trock, Bruce ; Lance, Raymond S. ; Bigley, Joseph W. ; Van Criekinge, Wim ; Epstein, Jonathan Ira. / Clinical validation of an epigenetic assay to predict negative histopathological results in repeat prostate biopsies. In: Journal of Urology. 2014 ; Vol. 192, No. 4. pp. 1081-1087.
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abstract = "Purpose The DOCUMENT multicenter trial in the United States validated the performance of an epigenetic test as an independent predictor of prostate cancer risk to guide decision making for repeat biopsy. Confirming an increased negative predictive value could help avoid unnecessary repeat biopsies. Materials and Methods We evaluated the archived, cancer negative prostate biopsy core tissue samples of 350 subjects from a total of 5 urological centers in the United States. All subjects underwent repeat biopsy within 24 months with a negative (controls) or positive (cases) histopathological result. Centralized blinded pathology evaluation of the 2 biopsy series was performed in all available subjects from each site. Biopsies were epigenetically profiled for GSTP1, APC and RASSF1 relative to the ACTB reference gene using quantitative methylation specific polymerase chain reaction. Predetermined analytical marker cutoffs were used to determine assay performance. Multivariate logistic regression was used to evaluate all risk factors. Results The epigenetic assay resulted in a negative predictive value of 88{\%} (95{\%} CI 85-91). In multivariate models correcting for age, prostate specific antigen, digital rectal examination, first biopsy histopathological characteristics and race the test proved to be the most significant independent predictor of patient outcome (OR 2.69, 95{\%} CI 1.60-4.51). Conclusions The DOCUMENT study validated that the epigenetic assay was a significant, independent predictor of prostate cancer detection in a repeat biopsy collected an average of 13 months after an initial negative result. Due to its 88{\%} negative predictive value adding this epigenetic assay to other known risk factors may help decrease unnecessary repeat prostate biopsies.",
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AU - Gee, Jason R.

AU - Troyer, Dean A.

AU - Rieger-Christ, Kimberly

AU - Jones, J. Stephen

AU - Magi-Galluzzi, Cristina

AU - Mangold, Leslie A.

AU - Trock, Bruce

AU - Lance, Raymond S.

AU - Bigley, Joseph W.

AU - Van Criekinge, Wim

AU - Epstein, Jonathan Ira

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N2 - Purpose The DOCUMENT multicenter trial in the United States validated the performance of an epigenetic test as an independent predictor of prostate cancer risk to guide decision making for repeat biopsy. Confirming an increased negative predictive value could help avoid unnecessary repeat biopsies. Materials and Methods We evaluated the archived, cancer negative prostate biopsy core tissue samples of 350 subjects from a total of 5 urological centers in the United States. All subjects underwent repeat biopsy within 24 months with a negative (controls) or positive (cases) histopathological result. Centralized blinded pathology evaluation of the 2 biopsy series was performed in all available subjects from each site. Biopsies were epigenetically profiled for GSTP1, APC and RASSF1 relative to the ACTB reference gene using quantitative methylation specific polymerase chain reaction. Predetermined analytical marker cutoffs were used to determine assay performance. Multivariate logistic regression was used to evaluate all risk factors. Results The epigenetic assay resulted in a negative predictive value of 88% (95% CI 85-91). In multivariate models correcting for age, prostate specific antigen, digital rectal examination, first biopsy histopathological characteristics and race the test proved to be the most significant independent predictor of patient outcome (OR 2.69, 95% CI 1.60-4.51). Conclusions The DOCUMENT study validated that the epigenetic assay was a significant, independent predictor of prostate cancer detection in a repeat biopsy collected an average of 13 months after an initial negative result. Due to its 88% negative predictive value adding this epigenetic assay to other known risk factors may help decrease unnecessary repeat prostate biopsies.

AB - Purpose The DOCUMENT multicenter trial in the United States validated the performance of an epigenetic test as an independent predictor of prostate cancer risk to guide decision making for repeat biopsy. Confirming an increased negative predictive value could help avoid unnecessary repeat biopsies. Materials and Methods We evaluated the archived, cancer negative prostate biopsy core tissue samples of 350 subjects from a total of 5 urological centers in the United States. All subjects underwent repeat biopsy within 24 months with a negative (controls) or positive (cases) histopathological result. Centralized blinded pathology evaluation of the 2 biopsy series was performed in all available subjects from each site. Biopsies were epigenetically profiled for GSTP1, APC and RASSF1 relative to the ACTB reference gene using quantitative methylation specific polymerase chain reaction. Predetermined analytical marker cutoffs were used to determine assay performance. Multivariate logistic regression was used to evaluate all risk factors. Results The epigenetic assay resulted in a negative predictive value of 88% (95% CI 85-91). In multivariate models correcting for age, prostate specific antigen, digital rectal examination, first biopsy histopathological characteristics and race the test proved to be the most significant independent predictor of patient outcome (OR 2.69, 95% CI 1.60-4.51). Conclusions The DOCUMENT study validated that the epigenetic assay was a significant, independent predictor of prostate cancer detection in a repeat biopsy collected an average of 13 months after an initial negative result. Due to its 88% negative predictive value adding this epigenetic assay to other known risk factors may help decrease unnecessary repeat prostate biopsies.

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