Objectives. Measurement of the percentage of free prostate-specific antigen (%FPSA) in serum can improve the specificity of prostate cancer screening. We evaluated the ability of %FPSA to predict pathologic features of screen-detected clinically localized prostate cancer. Methods. We evaluated the correlation between %FPSA in serum before cancer diagnosis and the pathologic features of the cancers detected in 108 men with clinically localized prostate cancer who were treated with radical prostatectomy and for whom complete embedding of the radical prostatectomy specimen was performed. Ninety-seven men (90%) had a previous negative screening evaluation before prostate cancer was detected. Results. There was a negative correlation of %FPSA with penetration of cancer through the prostatic capsule, cancerous surgical margins, Gleason score, percentage of cancer in the gland, and tumor volume (r = -0.2 to -0.4). After controlling for other preoperative predictors, %FPSA predicted capsular penetration (adjusted odds ratio [OR] 1.6, 95% confidence interval [Cl] 1.1 to 2.4, for each 5% decrease in %FPSA) and cancer volume 0.5 cc or greater (adjusted OR 1.6, 95% Cl 1.1 to 2.3). Preoperative %FPSA also predicted possibly harmless cancer (OR 1.5, 95% Cl 1.1 to 2.2, for each 5% increase in %FPSA). Conclusions. In a select group of men for whom cancer was detected early via screening, a lower %FPSA in serum suggests a potentially more threatening cancer. This information may aid patients and clinicians in making more informed decisions about the management of prostate cancer, such as selecting patients for watchful waiting. However, more research is needed to determine the performance characteristics of %FPSA in clinical practice.
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