title: A prospective, multicenter, National Cancer Institute Early Detection Research Network study of [-2]proPSA: improving prostate cancer detection and correlating with cancer aggressiveness.
abstract: BACKGROUND
  The free prostate-specific antigen (PSA) isoform, [-2]proPSA, has been shown to be associated with prostate cancer. The study objective was to characterize the clinical utility of serum [-2]proPSA for prostate cancer detection and assess its association with aggressive disease.
  
  
  METHODS
  From among 669 subjects in a prospective prostate cancer detection study at four National Cancer Institute Early Detection Research Network clinical validation centers, 566 were eligible. Serum PSA, free PSA, and [-2]proPSA were measured (Beckman Coulter Access 2 Analyzer).
  
  
  RESULTS
  Two hundred and forty-five (43%) of the 566 participants had prostate cancer on biopsy. At 70% specificity, the sensitivity of %[-2]proPSA ([-2]proPSA/fPSA) was 54% [95% confidence interval (CI), 48-61%; null hypothesis, 40%]. Including %[-2]proPSA in a multivariate prediction model incorporating PSA and %fPSA improved the performance (P<0.01). In the 2 to 4 ng/mL PSA range, %[-2]proPSA outperformed %fPSA (receiver operator characteristic-areas under the curve, 0.73 versus 0.61; P=0.01). At 80% sensitivity, %[-2]proPSA had significantly higher specificity (51.6%; 95% CI, 41.2-61.8%) than PSA (29.9%; 95% CI, 21.0-40.0%) and %fPSA (28.9%; 95% CI, 20.1-39.0%). In the 2 to 10 ng/mL PSA range, a multivariate model had significant improvement (area under the curve, 0.76) over individual PSA forms (P<0.01 to <0.0001). At 80% sensitivity, the specificity of %[-2]proPSA (44.9%; 95% CI, 38.4-51.5%) was significantly higher than PSA (30.8%; 95% CI, 24.9-37.1%) and relatively higher than %fPSA (34.6%; 95% CI, 28.5-41.4%). %[-2]proPSA increased with increasing Gleason score (P<0.001) and was higher in aggressive cancers (P=0.03).
  
  
  CONCLUSIONS
  In this prospective study, %[-2]proPSA showed potential clinical utility for improving prostate cancer detection and was related to the risk of aggressive disease.
  
  
  CONCLUSIONS
  The addition of %[-2]proPSA could affect the early detection of prostate cancer.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, 600 North Wolfe Street, Meyer B-125, Baltimore, MD 21287, USA. lsokoll@jhmi.edu
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Sokoll
authors.forename: Martin G
authors.initials: MG
authors.lastname: Sanda
authors.forename: Ziding
authors.initials: Z
authors.lastname: Feng
authors.forename: Jacob
authors.initials: J
authors.lastname: Kagan
authors.forename: Isaac A
authors.initials: IA
authors.lastname: Mizrahi
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Broyles
authors.forename: Alan W
authors.initials: AW
authors.lastname: Partin
authors.forename: Sudhir
authors.initials: S
authors.lastname: Srivastava
authors.forename: Ian M
authors.initials: IM
authors.lastname: Thompson
authors.forename: John T
authors.initials: JT
authors.lastname: Wei
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Chan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D008297:Male; D008875:Middle Aged; D054547:National Cancer Institute (U.S.); D009367:Neoplasm Staging; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D012372:ROC Curve; D014481:United States
chemical_list: D017430:Prostate-Specific Antigen
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