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A Prospective Multicenter Clinical Trial

William J. Catalona, MD; Alan W. Partin, MD, PhD; Kevin M. Slawin, MD; Michael K. Brawer, MD; Robert C. Flanigan, MD; Anup Patel, MD; Jerome P. Richie, MD; Jean B. deKernion, MD; Patrick C. Walsh, MD; Peter T. Scardino, MD; Paul H. Lange, MD; Eric N. P. Subong, MS; Robert E. Parson, MS; Gail H. Gasior, BA; Kathleen G. Loveland, BS; Paula C. Southwick, PhD

JAMA. 1998;279:1542-1547.

Context.— The percentage of free prostate-specific antigen (PSA) in serum has been shown to enhance the specificity of PSA testing for prostate cancer detection, but earlier studies provided only preliminary cutoffs for clinical use.

Objective.— To develop risk assessment guidelines and a cutoff value for defining abnormal percentage of free PSA in a population of men to whom the test would be applied.

Design.— Prospective blinded study using the Tandem PSA and free PSA assays (Hybritech Inc, San Diego, Calif).

Setting.— Seven nationwide university medical centers.

Participants.— A total of 773 men (379 with prostate cancer, 394 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 histologically confirmed diagnosis.

Main Outcome Measures.— A percentage of free PSA cutoff that maintained 95% sensitivity for prostate cancer detection, and probability of cancer for individual patients.

Results.— The percentage of free PSA may be used in 2 ways: as a single cutoff (ie, perform a biopsy for all patients at or below a cutoff of 25% free PSA) or as an individual patient risk assessment (ie, base biopsy decisions on each patient's risk of cancer). The 25% free PSA cutoff detected 95% 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 was associated with a higher risk of cancer (range, 8%-56%). In the multivariate model used, the percentage of free PSA was an independent predictor of prostate cancer (odds ratio [OR], 3.2; 95% confidence interval [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, 0.92-1.11) in this cohort of subjects with total PSA values between 4.0 and 10.0 ng/mL.

Conclusions.— Use of the percentage of free PSA can reduce unnecessary biopsies in patients undergoing evaluation for prostate cancer, with a minimal loss in sensitivity in detecting cancer. A cutoff of 25% or less free PSA is recommended for patients with PSA values between 4.0 and 10.0 ng/mL and a palpably benign gland, regardless of patient age or prostate size. To our knowledge, this study is the largest series to date evaluating the percentage of free PSA in a population representative of patients in whom the test would be used in clinical practice.

From the Division of Urologic Surgery, Washington University School of Medicine, St Louis, Mo (Dr Catalona); Department of Urology, The Johns Hopkins Hospital, Baltimore, Md (Drs Partin and Walsh and Mr Subong); Baylor College of Medicine, Houston, Tex (Drs Slawin and Scardino); University of Washington, Seattle (Drs Brawer and Lange); Loyola University Medical Center, Maywood, Ill (Dr Flanigan); School of Medicine, University of California at Los Angeles, (Drs Patel and deKernion); Harvard Program in Urology, Brigham and Women's Hospital, Boston, Mass (Dr Richie); Department of Research and Development, Hybritech Inc, San Diego, Calif (Mr Parson, Mss Gasior and Loveland, and Dr Southwick).

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