4633 Background: The value of both PSA and DRE for prostate cancer detection have recently been called into question when examined in screening and prostatectomy series (NEJM 350:2239, J Urol 172:1297). The effectiveness of these parameters for detection of clinically significant cancer is not fully characterized. We studied their utility for the detection of aggressive prostate cancer (Gleason Score ≥ 7) in a referral population of men. Methods: Data were collected on 1,699 referred men with a serum PSA of ≤ 10 ng/ml who underwent a prostate biopsy (minimum 6 cores) between 1993 and 2004. Variables analyzed included: age, race, family history, DRE (normal vs. suspicious vs. cancer-likely) and PSA. Thirty percent of the data were randomly reserved for study validation. Logistic regression analysis was performed to estimate the odds ratio and the 95% confidence intervals. Results: Gleason grade ≥ 7 prostate cancer was detected in 157 subjects (9.2%). Using the model building data set (n = 1,184), independent predictors of Gleason ≥ 7 cancer were an elevated PSA and an abnormal DRE only (see table ). Based on these results, a clinically-applicable nomogram was constructed and using the independent validation set (n = 515). The area under the ROC was 0.70 for the model. Conclusions: Although the use of PSA and DRE have recently come under intense scrutiny, they independently predict the presence of aggressive prostate cancer in a contemporary referral population. Improvement in prostate-cancer survival associated with successful treatment of localized disease requires the successful early detection of aggressive prostate cancer. Our results demonstrate that PSA and DRE, currently recommended screening interventions by the ACS and AUA, remain useful for the detection of aggressive prostate cancer in the PSA era. [Table: see text] No significant financial relationships to disclose.