Biological variation of prostate specific antigen levels in serum: An evaluation of day-to-day physiological fluctuations in a well-defined cohort of 24 patients

Purpose: We evaluated the daily biological variation of serum prostate specific antigen (PSA) concentrations to determine the critical difference required between 2 consecutive PSA measurements that would indicate a significant elevation. Materials and Methods: A total of 24 men, grouped according to clinical diagnosis and PSA, underwent phlebotomy for 10 consecutive weekdays. Duplicate serum samples were measured using 3 separate lots of Tandem-E dagger and IMx double dagger PSA assays. The biological variation was calculated and the 2 PSA assay systems were compared. The critical difference was examined to determine the percent elevation necessary to indicate (with 95% confidence) that PSA had increased beyond what would be expected from biological and analytical variation. Results: The biological variation, defined in terms of percent coefficient of variation, had a log-normal distribution with a geometric mean of 7.3% coefficient of variation and a 95th percentile value of 19.2% coefficient of variation using the Tandem-E PSA assay. Assuming an analytical variation of 5% coefficient of variation, the median critical difference was 20.5% and the 95th percentile critical difference was 45.8%. There was no significant difference between the 2 PSA assay systems in biological variation. However, PSA concentrations measured by the IMx assay were consistently lower compared to values measured by the Tandem-E assay. Conclusions: Characterizing the biological variation of serum PSA assists in evaluating the significance of changes in serial PSA measurements. The degree of biological variation differs among patients, such that an increase between 2 consecutive PSA levels that is less than 20 to 46% may be due to biological and analytical variation. These data influence interpretation of repeated measurements of serum PSA with time.