title: New insights into the diagnostic accuracy of complexed and total prostate specific antigen using discordance analysis characteristics.
abstract: OBJECTIVE
  Comparison of diagnostic performances of total and complexed prostate specific antigen (tPSA, cPSA) using ROC curve analysis resulted in controversial interpretations. To overcome the biases due to analysis of subgroups selected by concentration ranges of only 1 marker the novel approach named discordance analysis characteristics is presented.
  
  
  METHODS
  DAC method includes only patients who are discordantly categorized by the tests under investigation using cutoffs with identical sensitivity. Within those patients parameters describing diagnostic accuracy are calculated. The systematic nature of the results is confirmed by varying the cutoffs. DAC method is demonstrated considering the example of cPSA and tPSA data from 2 prostate cancer studies with a total of 1,624 patients (study A and B, of 283 and 565 with as well as 417 and 359 men without prostate cancer, respectively). PSA concentrations were measured using the Bayer assays.
  
  
  RESULTS
  The DAC method proved that cPSA outperformed tPSA regarding the criteria diagnostic specificity and positive predictive value. Among discordantly tested patients cPSA detected patients with an about 2-fold higher risk to have prostate cancer and with a 3.6 to 5.5-fold better specificity than tPSA. Using cPSA instead of tPSA more than 10% of unnecessary biopsies could be avoided in the tPSA range of 3 to 5 ng/ml.
  
  
  CONCLUSIONS
  The superior diagnostic performance of cPSA in comparison with tPSA warrants the recommendation to use cPSA as initial test in prostate cancer diagnostics. The DAC method is generally recommended to replace comparative ROC analyses of subgroups to evaluate the diagnostic usefulness of markers.
authors.affiliation: Department of Urology, University Hospital Charité, Berlin, Bayer Vital GmbH, Leverkusen, and ACOMED Statistics, Leipzig, Germany. klaus.jung@charite.de
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
authors.forename: Michael
authors.initials: M
authors.lastname: Lein
authors.forename: Hermann
authors.initials: H
authors.lastname: Butz
authors.forename: Carsten
authors.initials: C
authors.lastname: Stephan
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Loening
authors.forename: Thomas
authors.initials: T
authors.lastname: Keller
mesh_terms: D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis*; D015203:Reproducibility of Results
chemical_list: D017430:Prostate-Specific Antigen