title: Proenzyme psa for the early detection of prostate cancer in the 2.5-4.0 ng/ml total psa range: preliminary analysis.
abstract: OBJECTIVE
  To determine the clinical utility of using proenzyme prostate-specific antigen (pPSA) for early detection of prostate cancer in the 2.5 to 4.0 ng/mL total PSA range. pPSA, the precursor form of PSA that contains a 7 amino acid leader peptide, and truncated forms such as [-2]pPSA and [-4]pPSA can be measured in serum by research immunoassay.
  
  
  METHODS
  Archival serum from 119 men (noncancer, 88; cancer, 31), obtained before biopsy and in the total PSA range of 2.5 to 4.0 ng/mL, were assayed for total PSA, free PSA (fPSA), and pPSA. pPSA was defined as the sum of the [-2], [-4], and [-7] forms, and the percent pPSA (%pPSA) was defined as pPSA/fPSA.
  
  
  RESULTS
  pPSA averaged 4.6% +/- 0.4% (SEM) of total PSA and 39.3% +/- 3.5% of fPSA. PSA and %fPSA values were similar between the noncancer and cancer groups, and %pPSA tended to be higher in the cancer group (50.1% +/- 4.4%) compared with the noncancer group (35.5% +/- 6.7%; P = 0.07). Using receiver operating characteristic analysis to assess clinical utility, the area under the curve for %pPSA was 0.688 compared with 0.567 for %fPSA. At a fixed sensitivity of 75%, the specificity was significantly greater for %pPSA at 59% compared with %fPSA at 33% (P <0.0001).
  
  
  CONCLUSIONS
  In the 2.5 to 4.0 ng/mL total PSA range, 75% of cancers can potentially be detected with 59% of unnecessary biopsies being spared using %pPSA; use of %fPSA would result in sparing only 33% of unnecessary biopsies. A large prospective clinical trial is needed to confirm these preliminary findings.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Sokoll
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Chan
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Mikolajczyk
authors.forename: Harry G
authors.initials: HG
authors.lastname: Rittenhouse
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Evans
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Linton
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Mangold
authors.forename: Phaedre
authors.initials: P
authors.lastname: Mohr
authors.forename: Georg
authors.initials: G
authors.lastname: Bartsch
authors.forename: Helmut
authors.initials: H
authors.lastname: Klocker
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Horninger
authors.forename: Alan W
authors.initials: AW
authors.lastname: Partin
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D003937:Diagnosis, Differential; D004792:Enzyme Precursors / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010173:Palpation; D017430:Prostate-Specific Antigen / Q000097:blood*; D011470:Prostatic Hyperplasia / Q000097:blood / Q000175:diagnosis; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis; D012372:ROC Curve; D011863:Radioimmunoassay / Q000706:statistics & numerical data; D012680:Sensitivity and Specificity
chemical_list: D004792:Enzyme Precursors; D017430:Prostate-Specific Antigen