Biological variation of total prostate-specific antigen: a survey of published estimates and consequences for clinical practice.
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.
Sölétormos
György
G
Department of Clinical Biochemistry, Hillerød Hospital, Hillerød, Denmark. geso@fa.dk
Semjonow
Axel
A
Sibley
Paul E C
PE
Lamerz
Rolf
R
Petersen
Per Hyltoft
PH
Albrecht
Walter
W
Bialk
Peter
P
Gion
Massimo
M
Junker
Frank
F
Schmid
Hans-Peter
HP
Van Poppel
Hein
H
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
D017430:Prostate-Specific Antigen