title: Biological variation of total prostate-specific antigen: a survey of published estimates and consequences for clinical practice.
abstract: BACKGROUND
  The objectives of this study were to determine whether a single result for total prostate-specific antigen (tPSA) can be used confidently to guide the need for prostate biopsy and by how much serial tPSA measurements must differ to be significant. tPSA measurements include both analytical and biological components of variation. The European Group on Tumor Markers conducted a literature survey to determine both the magnitude and impact of biological variation on single, the mean of replicate, and serial tPSA measurements.
  
  
  METHODS
  The survey yielded 27 studies addressing the topic, and estimates for the biological variation of tPSA could be derived from 12 of these studies.
  
  
  RESULTS
  The mean biological variation was 20% in the concentration range 0.1-20 microg/L for men over 50 years. The biological variation means that the one-sided 95% confidence interval (CI) of the dispersion for a single tPSA result is approximately 33%. Three replicate samples with one analysis on each narrow the one-sided 95% CI for the mean concentration to approximately 20% and facilitate decisions on prostate biopsy. During monitoring of serial measurements, the change needed for significance is approximately 50% (P <0.05).
  
  
  CONCLUSIONS
  The biological variation of tPSA has implications for screening, diagnosis, and monitoring. Single measurements may not be sufficiently precise for screening and diagnosis. Replicate samples and calculation of the mean concentration may improve precision by reducing the dispersion. Monitoring of tPSA requires an estimate of either the change needed for significance or, alternatively, of the significance of the change.
authors.affiliation: Department of Clinical Biochemistry, Hillerød Hospital, Hillerød, Denmark. geso@fa.dk
authors.forename: György
authors.initials: G
authors.lastname: Sölétormos
authors.forename: Axel
authors.initials: A
authors.lastname: Semjonow
authors.forename: Paul E C
authors.initials: PE
authors.lastname: Sibley
authors.forename: Rolf
authors.initials: R
authors.lastname: Lamerz
authors.forename: Per Hyltoft
authors.initials: PH
authors.lastname: Petersen
authors.forename: Walter
authors.initials: W
authors.lastname: Albrecht
authors.forename: Peter
authors.initials: P
authors.lastname: Bialk
authors.forename: Massimo
authors.initials: M
authors.lastname: Gion
authors.forename: Frank
authors.initials: F
authors.lastname: Junker
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Schmid
authors.forename: Hein
authors.initials: H
authors.lastname: Van Poppel
mesh_terms: D002940:Circadian Rhythm; D006801:Humans; D008297:Male; D008403:Mass Screening; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000175:diagnosis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D017430:Prostate-Specific Antigen