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The importance of screening for early-stage prostate cancer has been debated in the literature. However, there are well-established prognostic factors (Gleason score [GS], pretreatment prostate-specific antigen [PSA], and percent positive biopsy findings [%+Bx]) that predict biologically aggressive disease. These factors, together with a patient's age and general state of health, will permit physicians to project the effect of a prostate tumor over the patient's expected lifetime. This study was performed to determine the proportion of clinically significant prostate cancers diagnosed in a screened population.From 1991 through 2002, 977 patients with nonpalpable (T1c) prostate cancer were seen for evaluation and comprise the study group. Patients were classified according to pretreatment PSA level, GS, %+Bx, and age.Based on tumor characteristics alone, 130 patients were noted to be at high risk (GS = 8–10 or PSA level >20 ng/mL; or GS = 7 or PSA level >10-≤20 ng/mL and >50%+Bx), with a historical 4-year PSA control of 10% to 30% after definitive therapy. An additional 45 patients were at intermediate risk (GS = 7, PSA level >10-≤20 ng/mL, and 34%-50%+Bx), with a historical 4-year PSA control of 50% to 60% after definitive therapy. Additional patients were identified who had a cumulative anticipated prostate cancer mortality greater than 30% to 50% based on age and GS (GS = 7, age ≤70 years [n = 89]; GS = 6, age ≤65 years [n = 337]). The total at risk for clinically significant tumors was 601 (61.5%) of 977 patients.A significant proportion of patients with nonpalpable disease diagnosed as having prostate cancer by PSA screening have clinically significant cancers. This supports the continued use of PSA screening.