title: A Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate Cancer at Initial Biopsy.
abstract: OBJECTIVE
  Overdiagnosis and overtreatment of indolent prostate cancer (PCA) is a serious health issue in most developed countries. There is an unmet clinical need for noninvasive, easy to administer, diagnostic assays to help assess whether a prostate biopsy is warranted.
  
  
  OBJECTIVE
  To determine the performance of a novel urine exosome gene expression assay (the ExoDx Prostate IntelliScore urine exosome assay) plus standard of care (SOC) (ie, prostate-specific antigen [PSA] level, age, race, and family history) vs SOC alone for discriminating between Gleason score (GS)7 and GS6 and benign disease on initial biopsy.
  
  
  METHODS
  In training, using reverse-transcriptase polymerase chain reaction (PCR), we compared the urine exosome gene expression assay with biopsy outcomes in 499 patients with prostate-specific antigen (PSA) levels of 2 to 20 ng/mL. The derived prognostic score was then validated in 1064 patients from 22 community practice and academic urology clinic sites in the United States. Eligible participants included PCA-free men, 50 years or older, scheduled for an initial or repeated prostate needle biopsy due to suspicious digital rectal examination (DRE) findings and/or PSA levels (limit range, 2.0-20.0 ng/mL).
  
  
  METHODS
  Evaluate the assay using the area under receiver operating characteristic curve (AUC) in discrimination of GS7 or greater from GS6 and benign disease on initial biopsy.
  
  
  RESULTS
  In 255 men in the training target population (median age 62 years and median PSA level 5.0 ng/mL, and initial biopsy), the urine exosome gene expression assay plus SOC was associated with improved discrimination between GS7 or greater and GS6 and benign disease: AUC 0.77 (95% CI, 0.71-0.83) vs SOC AUC 0.66 (95% CI, 0.58-0.72) (P < .001). Independent validation in 519 patients' urine exosome gene expression assay plus SOC AUC 0.73 (95% CI, 0.68-0.77) was superior to SOC AUC 0.63 (95% CI, 0.58-0.68) (P < .001). Using a predefined cut point, 138 of 519 (27%) biopsies would have been avoided, missing only 5% of patients with dominant pattern 4 high-risk GS7 disease.
  
  
  CONCLUSIONS
  This urine exosome gene expression assay is a noninvasive, urinary 3-gene expression assay that discriminates high-grade (≥GS7) from low-grade (GS6) cancer and benign disease. In this study, the urine exosome gene expression assay was associated with improved identification of patients with higher-grade prostate cancer among men with elevated PSA levels and could reduce the total number of unnecessary biopsies.
authors.affiliation: Department of Urology, Columbia University, New York, New York.
authors.forename: James
authors.initials: J
authors.lastname: McKiernan
authors.affiliation: Department of Pathology, Icahn School of Medicine at Mt Sinai, New York, New York.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Donovan
authors.affiliation: Exosome Diagnostics, Cambridge, Massachusetts.
authors.forename: Vince
authors.initials: V
authors.lastname: O'Neill
authors.affiliation: Exosome Diagnostics, Cambridge, Massachusetts.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bentink
authors.affiliation: Exosome Diagnostics, Cambridge, Massachusetts.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Noerholm
authors.affiliation: Exosome Diagnostics, Cambridge, Massachusetts.
authors.forename: Susan
authors.initials: S
authors.lastname: Belzer
authors.affiliation: Exosome Diagnostics, Cambridge, Massachusetts.
authors.forename: Johan
authors.initials: J
authors.lastname: Skog
authors.affiliation: Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Kattan
authors.affiliation: Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Alan
authors.initials: A
authors.lastname: Partin
authors.affiliation: Division of Urologic Surgery, Washington University, St Louis, Missouri.
authors.forename: Gerald
authors.initials: G
authors.lastname: Andriole
authors.affiliation: Delaware Valley Urology, Voorhees, New Jersey.
authors.forename: Gordon
authors.initials: G
authors.lastname: Brown
authors.affiliation: Division of Urologic Surgery, University of Michigan, Ann Arbor.
authors.forename: John T
authors.initials: JT
authors.lastname: Wei
authors.affiliation: The Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Thompson
authors.affiliation: Department of Urology, University of California-San Francisco, San Francisco.
authors.forename: Peter
authors.initials: P
authors.lastname: Carroll
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000652:urine*; D001706:Biopsy; D055354:Exosomes / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000652:urine; D011467:Prostate / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D017430:Prostate-Specific Antigen