title: Diagnostic performance of PCA3 to detect prostate cancer in men with increased prostate specific antigen: a prospective study of 1,962 cases.
abstract: OBJECTIVE
  The detection of prostate cancer relies primarily on abnormal digital rectal examination or increased serum prostate specific antigen concentration. However, low positive predictive values result in many men with increased prostate specific antigen and/or suspicious digital rectal examination having a negative biopsy. We investigated the value of the PCA3 (prostate cancer gene 3) urine test in predicting the likelihood of diagnosis of cancer before biopsy.
  
  
  METHODS
  We performed a prospective, community based clinical trial to evaluate PCA3 score before any biopsy. This trial was conducted at 50 urology practices in the United States. Samples were obtained from 1,962 men with increased serum prostate specific antigen (greater than 2.5 ng/ml) and/or abnormal digital rectal examination before transrectal prostate needle biopsy. Study samples (urinary PCA3 and biopsies) were processed and analyzed by a central laboratory. Sensitivity-specificity analyses were conducted.
  
  
  RESULTS
  A total of 1,913 urine samples (97.5%) were adequate for PCA3 testing. Of 802 cases diagnosed with prostate cancer 222 had high grade prostatic intraepithelial neoplasia or atypical small acinar proliferation and were suspicious for cancer, whereas 889 cases were benign. The traditional PCA3 cutoff of 35 reduced the number of false-positives from 1,089 to 249, a 77.1% reduction. However, false-negatives (missed cancers) increased significantly from 17 to 413, an increase of more than 2,300%. Lowering the PCA3 cutoff to 10 reduced the number of false-positives 35.4% and false-negatives only increased 5.6%.
  
  
  CONCLUSIONS
  Urinary PCA3 testing in conjunction with prostate specific antigen has the potential to significantly decrease the number of unnecessary prostate biopsies.
authors.affiliation: University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, USA. david.crawford@ucdenver.edu
authors.forename: E David
authors.initials: ED
authors.lastname: Crawford
authors.forename: Kyle O
authors.initials: KO
authors.lastname: Rove
authors.forename: Edouard J
authors.initials: EJ
authors.lastname: Trabulsi
authors.forename: Junqi
authors.initials: J
authors.lastname: Qian
authors.forename: Krystyna P
authors.initials: KP
authors.lastname: Drewnowska
authors.forename: Jed C
authors.initials: JC
authors.lastname: Kaminetsky
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Huisman
authors.forename: Mark L
authors.initials: ML
authors.lastname: Bilowus
authors.forename: Sheldon J
authors.initials: SJ
authors.lastname: Freedman
authors.forename: W Lloyd
authors.initials: WL
authors.lastname: Glover
authors.forename: David G
authors.initials: DG
authors.lastname: Bostwick
mesh_terms: D000951:Antigens, Neoplasm / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000652:urine*
chemical_list: D000951:Antigens, Neoplasm; C479341:prostate cancer antigen 3, human; D017430:Prostate-Specific Antigen