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William J. Catalona, MD; Deborah S. Smith, PhD; Robert L. Wolfert, PhD; Tang J. Wang, PhD; Harry G. Rittenhouse, PhD; Timothy L. Ratliff, PhD; Robert B. Nadler, MD

JAMA. 1995;274(15):1214-1220.

Abstract
Objective.
—To evaluate measurement of percentage of free prostate-specific antigen (PSA) in serum to improve the specificity of prostate cancer screening in men with serum PSA levels between 4.1 and 10.0 ng/mL.

Design.
—Retrospective, nonrandomized analysis using a research assay for measuring free PSA in frozen serum from men with a spectrum of prostate sizes and digital rectal examination results.

Setting.
—General community outpatient prostate cancer screening program at a university center.

Patients.
—One hundred thirteen men aged 50 years or older, 99% of whom were white, with serum PSA concentrations of 4.1 to 10.0 ng/mL, including 63 men with histologically confirmed benign prostatic hyperplasia, 30 with prostate cancer with an enlarged gland, and 20 with cancer with a normal-sized gland. All study volunteers had undergone prostatic ultrasonography and biopsy.

Main Outcome Measures.
—Percentage of free PSA in serum and percentage of free PSA cutoff that maintained at least 90% sensitivity for prostate cancer detection.

Results.
—Median percentage of free PSA was 9.2% in men with cancer and a normal-sized gland, 15.9% in men with cancer and an enlarged gland, and 18.8% in men with benign prostatic hyperplasia (P<.001). The percentage of free PSA cutoff was higher in men with an enlarged gland and in those with a palpably benign gland. In men with an enlarged, palpably benign gland, a free PSA cutoff of 23.4% or lower detected at least 90% of cancers and would have eliminated 31.3% of negative biopsies.

Conclusions.
—Measurement of percentage of free serum PSA improves specificity of prostate cancer screening in selected men with elevated total serum PSA levels and can reduce unnecessary prostate biopsies with minimal effects on the cancer detection rate; however, further studies are needed to define optimal cutoffs. Final evaluation of PSA screening also must consider the ability of current treatments to improve the prognosis of screen-detected prostate cancer.

(JAMA. 1995;274:1214-1220)

Author Affiliations
From the Division of Urologic Surgery, Department of Surgery, Washington University School of Medicine, St Louis, Mo (Drs Catalona, Smith, Ratliff, and Nadler), and Department of Research and Development, Hybritech Incorporated, San Diego, Calif (Drs Wolfert, Wang, and Rittenhouse).

Footnotes
Reprint requests to Division of Urologic Surgery, 4960 Children's PI, St Louis, MO 63110 (Dr Catalona).

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