USE OF THE PERCENTAGE OF FREE PROSTATE-SPECIFIC ANTIGEN TO ENHANCE DIFFERENTIATION OF PROSTATE-CANCER FROM BENIGN PROSTATIC DISEASE - A PROSPECTIVE MULTICENTER CLINICAL-TRIAL

Context.-The percentage of free prostate-specific antigen (PSA) in ser um has been shown to enhance the specificity of PSA testing for prosta te cancer detection, but earlier studies provided only preliminary cut offs for clinical use. Objective.-To develop risk assessment guideline s and a cutoff value for defining abnormal percentage of free PSA in a population of men to whom the test would be applied. Design.-Prospect ive blinded study using the Tandem PSA and free PSA assays (Hybritech Inc, San Diego, Calif). Setting.-Seven nationwide university medical c enters. Participants.-A total of 773 men (379 with prostate cancer, 39 4 with benign prostatic disease) 50 to 75 years of age with a palpably benign prostate gland, PSA level of 4.0 to 10.0 ng/mL, and histologic ally confirmed diagnosis. Main Outcome Measures.-A percentage of free PSA cutoff that maintained 95% sensitivity for prostate cancer detecti on, and probability of cancer for individual patients. Results.-The pe rcentage of free PSA may be used in 2 ways: as a single cutoff tie, pe rform a biopsy for all patients at or below a cutoff of 25% free PSA) or as an individual patient risk assessment tie, base biopsy decisions on each patient's risk of cancer). The 25% free PSA cutoff detected 9 5% of cancers while avoiding 20% of unnecessary biopsies. The cancers associated with greater than 25% free PSA were more prevalent in older patients, and generally were less threatening in terms of tumor grade and volume. For individual patients, a lower percentage of free PSA w as associated with a higher risk of cancer (range, 8%-56%), In the mul tivariate model used, the percentage of free PSA was an independent pr edictor of prostate cancer (odds ratio [OR], 3.2; 95% confidence inter val [CI], 2.5-4.1; P<.001) and contributed significantly more than age (OR, 1.2; 95% CI, 0.92-1.55) or total PSA level (OR, 1.0; 95% CI, 0.9 2-1.11) in this cohort of subjects with total PSA values between 4.0 a nd 10.0 ng/mL. Conclusions.-Use of the percentage of free PSA can redu ce unnecessary biopsies in patients undergoing evaluation for prostate cancer, with a minimal loss in sensitivity in detecting cancer. A cut off of 25% or less free PSA is recommended for patients with PSA value s between 4.0 and 10.0 ng/mL and a palpably benign gland, regardless o f patient age or prostate size. To our knowledge, this study is the la rgest series to date evaluating the percentage of free PSA in a popula tion representative of patients in whom the test would be used in clin ical practice.