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 diffe rence required between 2 consecutive PSA measurements that would indic ate 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 us ing 3 separate lots of Tandem-E dagger and IMx double dagger PSA assay s. 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 analy tical variation. Results: The biological variation, defined in terms o f percent coefficient of variation, had a log-normal distribution with a geometric mean of 7.3% coefficient of variation and a 95th percenti le value of 19.2% coefficient of variation using the Tandem-E PSA assa y. Assuming an analytical variation of 5% coefficient of variation, th e median critical difference was 20.5% and the 95th percentile critica l difference was 45.8%. There was no significant difference between th e 2 PSA assay systems in biological variation. However, PSA concentrat ions measured by the IMx assay were consistently lower compared to val ues measured by the Tandem-E assay. Conclusions: Characterizing the bi ological variation of serum PSA assists in evaluating the significance of changes in serial PSA measurements. The degree of biological varia tion differs among patients, such that an increase between 2 consecuti ve 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.