IMPACT OF AGE ON COMPLEXED PSA LEVELS IN MEN WITH TOTAL PSA LEVELS OF UP TO 20 ng/mL ANDREAS P. BERGER, CAROL CHELI, RONALD LEVINE, HELMUT KLOCKER, GEORG BARTSCH, AND WOLFGANG HORNINGER ABSTRACT Objectives. To evaluate the relationship between age and complexed prostate-specific antigen (cPSA) in healthy white men with no evidence of prostatic disease and total PSA (tPSA) levels of 0 to 20 ng/mL. Methods. A total of 10,530 tests for cPSA and tPSA in men between 40 and 79 years old were performed at Innsbruck University, Austria, between 2001 and 2002. After excluding 263 patients because of follow-up biopsy findings indicating prostatic disease, 10,267 PSA tests were available for study. All serum samples were analyzed using the Bayer Immuno 1 cPSA and tPSA assays. cPSA and tPSA values were determined in subjects with tPSA levels between 0 and 20 ng/mL. The concentrations were calculated for the 50th, 90th, and 95th percentiles of four age groups (40 to 49, 50 to 59, 60 to 69, and 70 to 79 years). For statistical analysis, the Kruskal-Wallis test was used. The 95th percentile was defined as the upper limit of normal. Results. A total of 10,267 PSA tests were available for study. cPSA and tPSA levels correlated linearly and positively with age (P 0.001). Percent free PSA showed a significant increase with age (P 0.001), which may be attributed to the increase in prostate volume with advancing age. Conclusions. Both cPSA and tPSA levels were found to increase with age. The low tPSA and cPSA levels observed at the 95th percentile in men aged 40 to 59 years suggest that lower cutoff values should be used in place of the currently accepted tPSA level of 4 ng/mL. Lower cutoff values may help improve the detection of prostate cancer among otherwise healthy men. UROLOGY 62: 840–844, 2003. © 2003 Elsevier Inc. P rostate-specific antigen (PSA) is the most widely used serum tumor marker for both prostate cancer diagnosis and follow-up after treat- ment. However, this marker is not specific for pros- tate cancer but for prostatic tissue. The levels of this physiologic protease are known to be influ- enced by a number of exogenous and endogenous factors such as large prostate size, prostatitis, ure- thral instrumentation, and urinary tract infection, as well as prostatic ischemia and/or infarction. Conversely, PSA levels may be in the normal range despite the presence of prostate cancer, which makes PSA a less than perfect tumor marker for prostate malignancy. Because lowering the PSA threshold levels will increase the number of biop- sies, additional parameters are required to improve the selection of patients with potentially curable prostate cancer. Such parameters are of particular relevance in patients with a high benefit/risk ratio, because approximately 25% of men with PSA levels in the 4 to 10-ng/mL range will present with pros- tate cancer. 1 The usefulness of total PSA (tPSA) has been limited by its lack of specificity owing to PSA elevation attributable to benign disease. Recent studies have demonstrated that the specificity of complexed PSA (cPSA) is superior to that of tPSA, not only in the 4 to 10-ng/mL range, 1–3 but also in the low PSA range of 2 to 4 ng/mL. 4 However, in contrast, studies have been published that have suggested cPSA is equivalent to tPSA for the early detection of prostate cancer. 5,6 To optimize the detection rates of potentially curable prostate cancer, appropriate age-specific reference ranges for cPSA are essential. The aim of the present study was to evaluate the distribution of cPSA in a population of apparently healthy white men with no clinical evidence of prostate cancer to improve the specificity of PSA screening for prostate cancer and to investigate the From the Department of Urology, University of Innsbruck, Inns- bruck, Austria; and Bayer Corporation, Tarrytown, New York Reprint requests: Andreas P. Berger, M.D., Department of Urology, University of Innsbruck, Anichstrasse 35, Innsbruck A-6020, Austria Submitted: April 14, 2003, accepted (with revisions): June 10, 2003 ADULT UROLOGY © 2003 ELSEVIER INC. 0090-4295/03/$30.00 840 ALL RIGHTS RESERVED doi:10.1016/S0090-4295(03)00671-X