2158 COMBINING TMPRSS2:ERG AND PCA3 IN POST-DRE URINE WITH SERUM PSA TO IDENTIFY PROSTATE BIOPSY CANDIDATES: DEVELOPMENT AND VERIFICATION OF A CLINICALLY PRACTICAL ALGORITHM (2010)

You have accessJournal of UrologyProstate Cancer: Detection and Screening V1 Apr 20102158 COMBINING TMPRSS2:ERG AND PCA3 IN POST-DRE URINE WITH SERUM PSA TO IDENTIFY PROSTATE BIOPSY CANDIDATES: DEVELOPMENT AND VERIFICATION OF A CLINICALLY PRACTICAL ALGORITHM Scott Tomlins, Martin Sanda, Simpa Salami, Bharathi Laxman, Meredith Regan, Javed Siddiqui, David Rickman, Douglas Scherr, Mark Rubin, John Wei, and Arul Chinnaiyan Scott TomlinsScott Tomlins Ann Arbor, MI , Martin SandaMartin Sanda Boston, MA , Simpa SalamiSimpa Salami Boston, MA , Bharathi LaxmanBharathi Laxman Ann Arbor, MI , Meredith ReganMeredith Regan Boston, MA , Javed SiddiquiJaved Siddiqui Ann Arbor, MI , David RickmanDavid Rickman New York, NY , Douglas ScherrDouglas Scherr New York, NY , Mark RubinMark Rubin New York, NY , John WeiJohn Wei Ann Arbor, MI , and Arul ChinnaiyanArul Chinnaiyan Ann Arbor, MI View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.2260AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To develop a clinically useful algorithm combining serum PSA with TMPRSS2:ERG fusion (T-erg) and PCA3 detected in urine collected after DRE to predict prostate cancer on subsequent biopsy. METHODS Serum PSA and post-DRE urine was collected before prostate biopsy in a prospective multicenter EDRN cohort (N=353). In a pilot cohort (N=48) PCA3 and T-erg fusion were detected by RT-PCR of urine sediment; their performance in predicting prostate cancer was evaluated and a multivariable algorithm to predict prostate cancer was developed by logistic regression. Performance of the multiplex algorithm was verified in 305 men with T-erg and PCA3 measured by GenProbe Transcription Mediated Amplification (TMA) of post DRE whole urine. RESULTS In the pilot cohort PCA3 had the highest sensitivity (93%) in predicting prostate cancer diagnosis and T-erg had the highest specificity (87%). Combining serum PSA with urine PCA3 and T-erg in a multivariate algorithm optimized for clinical utility improved cancer prediction (model AUC = 0.88; at 80% sensitivity, specificity = 90%) over PSA alone (AUC = 0.72). The algorithm recommends biopsy if either T-erg or PCA3 is positive when PSA < 10ng/ml, and whenever PSA > 10ng/ml. Performance of this algorithm was tested in 305 subjects by TMA whole urine assay for T-erg and PCA3; 299 were informative and 45% had prostate cancer. The clinical algorithm based on PSA, T-erg and PCA3 combined (AUC = 0.75) performed better than for PSA alone (AUC = 0.59) in predicting prostate cancer diagnosis (p<0.05, Figure). At sensitivity = 82%, the multiplex algorithm specificity was 60%, compared to 23% specificity for PSA alone (corresponding to PSA = 3.5 ng/ml). Use of the model algorithm would have avoided unnecessary biopsy in 32% of men in the validation cohort. CONCLUSIONS A clinically practical algorithm that recommends biopsy for all patients with PSA >10ng/ml, while restricting biopsy among those with PSA <10ng/ml to men who have either T-erg or PCA3 present in post-DRE urine, outperformed PSA in predicting prostate cancer. This algorithm would eliminate nearly than one third of prostate biopsies without substantive compromise of cancer detection. Prospective multi-center validation is warranted. *MS, JW & AC share senior authorship © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e839 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.Metrics Author Information Scott Tomlins Ann Arbor, MI More articles by this author Martin Sanda Boston, MA More articles by this author Simpa Salami Boston, MA More articles by this author Bharathi Laxman Ann Arbor, MI More articles by this author Meredith Regan Boston, MA More articles by this author Javed Siddiqui Ann Arbor, MI More articles by this author David Rickman New York, NY More articles by this author Douglas Scherr New York, NY More articles by this author Mark Rubin New York, NY More articles by this author John Wei Ann Arbor, MI More articles by this author Arul Chinnaiyan Ann Arbor, MI More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...