TOTAL AND TRANSITION ZONE PROSTATE VOLUME AND AGE: HOW DO THEY AFFECT THE UTILITY OF PSA-BASED DIAGNOSTIC PARAMETERS FOR EARLY PROSTATE CANCER DETECTION? BOB DJAVAN, ALEXANDRE R. ZLOTTA, MESUT REMZI, KEYWAN GHAWIDEL, BERND BURSA, STEPHAN HRUBY, ROSWITHA WOLFRAM, CLAUDE C. SCHULMAN, AND MICHAEL MARBERGER ABSTRACT Objectives. To define the role of total prostate (TP) volume, transition zone (TZ) volume, and age as determinants of the utility of prostate-specific antigen (PSA)-based diagnostic parameters for early detection of prostate cancer (PCa) in a prospective multicenter study. Methods. The study participants were 974 consecutive men with serum total PSA (tPSA) levels of 4 to 10 ng/mL who were referred for early PCa detection or lower urinary tract symptoms. All patients underwent prostate ultrasound examination and sextant biopsy with two additional TZ biopsies. In patients with negative initial biopsies, repeated biopsies were performed at 6 weeks. tPSA, the free/total PSA ratio (f/t PSA), PSA density of the TZ (PSA-TZ), PSA density (PSAD), and PSA velocity (PSAV) were determined and compared across TP volume strata of 30 cm 3 or less and greater than 30 cm 3 , TZ volume strata of 20 cm 3 or less and greater than 20 cm 3 , and various age groups to evaluate the need for volume and/or age-specific reference ranges. Results. PCa was found in 345 (35.4%) of 974 patients and benign prostatic tissue was found in 629 (64.6%) of 947 patients. Across TP volume strata, significantly higher values of tPSA (P 0.01), PSA-TZ, PSAD (P 0.001), and PSAV (P 0.05) and lower values of f/t PSA (P 0.001) were observed in patients with PCa than in those without PCa. Similar results were obtained with respect to TZ volume strata, except in the case of PSAV (P 0.05). tPSA, PSA-TZ, and PSAD were significantly higher (P 0.05) in patients with PCa than in those without PCa for all corresponding age ranges. In patients with PCa, f/t PSA was significantly lower (P 0.001) within the same age ranges. Within each group (PCa or benign), f/t PSA, PSAD, PSA-TZ, and PSAV values were unaffected by age strata. However, PSA parameters dependent on prostate volume (PSAD, PSA-TZ) were statistically lower (P 0.001) in prostates with a higher TP volume (greater than 30 cm 3 ) and TZ volume (greater than 20 cm 3 ); f/t PSA values were unaffected by TP and TZ volumes. Conclusions. f/t PSA and PSA-TZ were the most powerful parameters to differentiate between benign prostatic tissue and PCa. f/t PSA was the sole parameter unaffected by age and prostate volume. We believe new volume-specific cutpoints, as presented in the current study, should be employed when using PSAD and PSA-TZ for the early detection of PCa. UROLOGY 54: 846–852, 1999. © 1999, Elsevier Science Inc. S tandard assays of total serum prostate-specific antigen (tPSA) are currently a mainstay for monitoring disease progression and treating pa- tients with prostate cancer (PCa). Nevertheless, by themselves these measurements do not afford suf- ficient sensitivity and specificity for early detection or staging of PCa. In the PSA range of 4 to 10 ng/mL, one third of men can be diagnosed with PCa, with the remainder having benign disease. Consequently, in this PSA range, false-positive re- sults and unnecessary biopsies can be frequent. 1–5 One approach is the determination of the free/ total PSA ratio (f/t PSA). A lower f/t PSA has been observed in patients with PCa than in patients with benign prostatic hyperplasia (BPH). Two further From the Department of Urology, University of Vienna, Vienna, Austria; Department of Urology, University Clinics of Brussels, Brussels, Belgium; and Department of Oncology, University of Vienna, Vienna, Austria Reprint requests: Bob Djavan, M.D., Ph.D., Department of Urology, University of Vienna, Wa ¨ hringer Gu ¨ rtel 18-20, Vienna A-1090 Austria Submitted: April 2, 1999, accepted (with revisions): May 27, 1999 ADULT UROLOGY © 1999, ELSEVIER SCIENCE INC. 0090-4295/99/$20.00 846 ALL RIGHTS RESERVED PII S0090-4295(99)00329-5