Oncology Population-based Analysis of Normal Total PSA and Percentage of Free/Total PSA Values: Results From Screening Cohort Umberto Capitanio, Paul Perrotte, Laurent Zini, Nazareno Suardi, Elie Antebi, Vincent Cloutier, Claudio Jeldres, Shahrokh F. Shariat, Alain Duclos, Philippe Arjane, Fred Saad, Francesco Montorsi, and Pierre I. Karakiewicz OBJECTIVES To examine the distribution of total prostate-specific antigen (tPSA) and percentage of free/total PSA (%f/tPSA) values in patients undergoing prostate cancer screening in Canada. METHODS The data from 4 consecutive annual prostate cancer screening events held in Montreal, Canada were examined with respect to age, tPSA, and %f/tPSA in 3222 men. RESULTS Within the entire cohort, the median PSA level was 1.0 ng/mL and the median %f/tPSA was 26%. Using the interquartile range around the median, the upper bound for tPSA was situated at 1.9 ng/mL and the lower bound for %f/tPSA was at 19%. The 90th percentile for the median tPSA was 3.8, and the 10th percentile for the median %f/tPSA was 14. PSA and %f/tPSA showed a relation with age. The 75th percentile for the median tPSA level in the age category 40-49, 50-59, 60-69, and 70-79 years was 1.1, 1.4, 2.6, and 3.6 ng/mL, respectively. The 25th percentile for the median %f/tPSA level in the age category 40-49, 50-59, 60-69, and 70-79 years was 19, 21, 18 and 19 ng/mL, respectively. CONCLUSIONS Our results can guide clinicians regarding the population-based distribution of serum tPSA and %f/tPSA values. Those values can be used for the purpose of counseling, as well as in the informed consent process before prostate biopsy. UROLOGY 73: 1323–1327, 2009. © 2009 Elsevier Inc. C ontroversy persists regarding the definition of a “normal” total serum prostate-specific antigen (tPSA) level. 1-12 The Prostate Cancer Preven- tion Trial data have demonstrated that a large proportion of men with a tPSA level of 2.5 ng/mL harbor prostate cancer (PCa). 8 Several other investigators have also re- ported on “normal” serum tPSA values that were well below the previously accepted cutoff of 4 ng/mL. 3,5-9,13-16 For example, in the Prostate Cancer Prevention Trial, Thompson et al. 8 detected PCa in 15.2% of men whose tPSA level was 4.0 ng/mL. Even in the presence of very low tPSA values (0.1-1.0 ng/mL), 16.7% had PCa on biopsy. 8 Fang et al. 5 relied on the Baltimore Longitudinal Study of Aging, which spanned 3 decades of follow-up, to demonstrate that a baseline tPSA level greater than the median for the age group 40-49 years (0.6 ng/mL) and 50-59 years (l.71 ng/mL) increased the risk of PCa 3.6 and 3.5 times, respectively. Loeb et al. 13 showed that a baseline tPSA level between the age-adjusted (40-49 vs 50-59 vs 60 years) median tPSA value (0.7, 0.9, and 1.4 ng/mL, respectively) and 2.5 ng/mL represents a sig- nificant risk factor (P  .001) for developing PCa of any grade. 13 Men aged 40-49 and 50-59 years had, respec- tively, 14.6 and 7.6 times the risk of PCa than men with a baseline tPSA equal to or less than the median. 13 These data indicate that the normal values are well below the previously used cutoff of 4 ng/mL and that even a cutoff of 2.5 ng/mL might be too high. 8,13,14 Because of the lack of established “normal” definitions, we assessed the distribution of tPSA in a large screening cohort of healthy men with no diagnosis of PCa. More- over, using the established value of the percentage of free/total PSA (%f/tPSA) in several multivariate models predicting the presence of PCa at needle biopsy, 17-19 we also examined the distribution of %f/tPSA. MATERIAL AND METHODS Patient Population The study group consisted of 3222 men with no known PCa who had participated in 1 of 4 annual PCa screening events, the P. I. Karakiewicz is partially supported by the University of Montreal Heath Center Urology Associates, Fonds de la Recherche en Santé du Québec, the University of Montreal Department of Surgery and the University of Montreal Health Center (CHUM) Foundation. From the Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Quebec, Canada; Department of Urology, Vita-Salute University San Raffaele, Milan, Italy; and Department of Urology, University of Montreal, Montreal, Quebec, Canada Reprint requests: Pierre I. Karakiewicz, M.D., F.R.C.S.C., Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center (CHUM), 1058 Rue Street, Denis, Montreal H2X 3J4 QC, Canada. E-mail: pierre.karakiewicz@ umontreal.ca Submitted: July 23, 2008, accepted (with revisions): October 6, 2008 © 2009 Elsevier Inc. 0090-4295/09/$34.00 1323 All Rights Reserved doi:10.1016/j.urology.2008.10.026