In a study population, can digital rectal examination (DRE), transrectal ultrasound (TRUS), and prostate specific antigen (PSA) (monoclonal) effectively detect the majority of clinically relevant cancer? If this is possible, the remaining patients could then be considered for chemopreventive protocols. The American Cancer Society/National Prostate Cancer Detection Project (ACS/NPCDP) had a cancer detection rate of 2.4% for its initial year utilizing PSA, DRE and TRUS. TRUS and PSA detected 73% more cancer than DRE alone. TRUS detected a greater percentage of cancers than DRE (85% vs. 64%). PSA was > or = 4 ng/ml for 66% of prostate cancer patients; 11% of cancer patients had PSA < 2 ng/ml. PSA decision levels based on gland volume detected a subgroup at the 95th percentile that had a nine-fold increased risk for cancer. In a separate study differentiating benign prostatic hypertrophy (BPH) and cancer, we found 0.12 +/- 0.13 ng/ml/gm for serum PSA (sPSA)/gm BPH. This study proved that predicted PSA (pPSA) = gland volume x 0.12; this equation also functioned at the 95th percentile for any individual patient. Individual patient assessment: 1. Entry level PSA = 2 ng/ml. 2. Those patients with PSA > 2 ng/ml have TRUS determination of gland volume (performed by technician). 3. pPSA = gland volume x 0.12. If sPSA > pPSA then: 4. (sPSA-pPSA)/2 = predicted volume (cc) of cancer; 5. 3 square root of volume of cancer = mean diameter (cm) of cancer. Thus, these results should detect the majority of clinically relevant cancer (> 0.5 cc). PSA combined with TRUS and DRE can identify high risk groups for cancer.