1738 IMPROVED PREDICTION OF PROSTATE BIOPSY OUTCOME BY INCORPORATING TMPRSS2:ERG AND OTHER RISK FACTORS INTO A LOGISTIC REGRESSION MODEL

Abstract

You have accessJournal of UrologyProstate Cancer: Detection and Screening I1 Apr 20101738 IMPROVED PREDICTION OF PROSTATE BIOPSY OUTCOME BY INCORPORATING TMPRSS2:ERG AND OTHER RISK FACTORS INTO A LOGISTIC REGRESSION MODEL James Amberson, John Day, James Cochran, William Harper, William Johnston, Naveen Kella, Isaac Koziol, George Patsias, and Thomas Williams James AmbersonJames Amberson Stratford, CT More articles by this author , John DayJohn Day San Diego, CA More articles by this author , James CochranJames Cochran Dallas, TX More articles by this author , William HarperWilliam Harper Columbus, GA More articles by this author , William JohnstonWilliam Johnston Hyannis, MA More articles by this author , Naveen KellaNaveen Kella San Antonio, TX More articles by this author , Isaac KoziolIsaac Koziol Richmond, VA More articles by this author , George PatsiasGeorge Patsias Wellington, FL More articles by this author , and Thomas WilliamsThomas Williams Sarasota, FL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1586AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The need exists for prostate cancer (PCa) markers with greater diagnostic accuracy. Although serum prostate specific antigen (sPSA) has high sensitivity for predicting prostate biopsy (PB) outcome, it has poor specificity leading to >60% negative biopsies. In this study, we evaluated the performance of a prototype quantitative TMPRSS2:ERG (T2:ERG) gene fusion urine assay for predicting PB outcome alone and in combination with other markers and risk factors. METHODS Patients referred for PB because of abnormal DRE or elevated sPSA were enrolled in a prospective clinical study at 7 community-based urology clinics located throughout the United States. Post-DRE first-catch urine specimens were collected from 471 subjects, who then had PB performed (minimum 12 cores). T2:ERG mRNA copies in samples were quantified using a transcription-mediated amplification assay and normalized to PSA mRNA copies. The prototype T2:ERG urine assay detects the gene fusion mRNA isoform TMPRSS2 exon 1 to ERG exon 4. Logistic regression (LR) analysis was used to determine the best combination of risk factors and biomarkers for predicting PB outcome. RESULTS In this study, 98% (463/471) of specimens yielded sufficient RNA for T2:ERG analysis. PCA3, sPSA and fPSA results were obtained for 453 subjects, and the positive PB rate was 44% (199/453). The T2:ERG urine assay showed high specificity (87%) and a sensitivity of 39% using a cutoff of 32. Combining T2:ERG with PCA3, sPSA, %fPSA, age, prostate volume, family history, race, DRE result and prior prostate biopsy in a cross-validated LR analysis led to significantly improved diagnostic accuracy (AUC=0.754, 95% CI=0.749-0.758) for predicting PB outcome. The complete model without T2:ERG had an AUC of 0.715 (95% CI=0.710-0.720). CONCLUSIONS In a prospective multi-center study, the T2:ERG urine assay demonstrated high specificity for predicting biopsy outcome; sensitivity was similar to the prevalence of T2:ERG gene fusions in prostate tumors. These data suggest that further improvement in diagnostic accuracy could be achieved using a nomogram that combines T2:ERG with other markers and risk factors for prostate cancer. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e671-e672 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information James Amberson Stratford, CT More articles by this author John Day San Diego, CA More articles by this author James Cochran Dallas, TX More articles by this author William Harper Columbus, GA More articles by this author William Johnston Hyannis, MA More articles by this author Naveen Kella San Antonio, TX More articles by this author Isaac Koziol Richmond, VA More articles by this author George Patsias Wellington, FL More articles by this author Thomas Williams Sarasota, FL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...