VARIATION OF FREE AND TOTAL PROSTATE-SPECIFIC ANTIGEN LEVELS - THE EFFECT ON THE PERCENT FREE TOTAL PROSTATE-SPECIFIC ANTIGEN/

Objective.-Recent studies have shown that calculations of the percent free/total prostate-specific antigen (PSA) improves the specificity of PSA testing. Characterizing the variability of free PSA and total PSA is necessary to evaluate the utility of an isolated free/total PSA me asurement. We investigated the total variation of free and total PSA l evels to determine how the percent free/total PSA was affected. Design .-Serum was obtained from nine urological patients on 5 different days over a 2-week period. Free and total PSA levels were measured on the day of collection. The total variation expressed in terms of percent c oefficient of variation (%CV) was calculated, and the biological varia tion was derived taking analytical variation into consideration. Setti ng.-Patients were from Seattle (Wash) Urological Associates, and sampl es were processed at the Dynacare Laboratory of Pathology, Seattle, Wa sh. Patients.-Nine men (aged 48 to 69 years) were evaluated; three had been diagnosed with prostate cancer, three with benign prostatic hype rplasia, one with chronic prostatitis, one with high-grade prostatic i ntraepithelial neoplasia, and one was clinically normal. Main Outcome Measures.-Total variation for free, total, and percent free/total PSA. Results.-The average total variation was 13.9% CV, 7.5% CV, and 10.6% CV for free, total, and percent free/total PSA, respectively. Biologi cal variation was derived to be 13.0% CV, 5.6% CV, and 8.0% CV for fre e, total, and percent free/total PSA, respectively. Conclusions.-When applied, these results suggest that there are significant random chang es in the numerator and denominator of the free PSA-total PSA ratio th at could result in clinical misinterpretation. Clinicians must be awar e that free PSA and total PSA levels will fluctuate owing to nonpathol ogic variation.