Introduction: As prostatic volume influences percent free prostate-specific antigen (PSA) in patients with prostate cancer, we evaluated whether percent free PSA density, which relates the serum percent free PSA to the volume of the prostate determined by transrectal ultrasound, could increase the specificity of cancer detection in men with normal digital rectal examinations and intermediate PSA levels. Materials and Methods: We prospectively evaluated 105 consecutive men with normal digital rectal examinations and serum PSA levels of 4.1–10.0 ng/ml. All patients underwent at least sextant prostate biopsies to establish the diagnosis. For detection of total and free PSA we used an Immulite free and total PSA assay. We compared PSA density, percent free PSA and percent free PSA density for their utility in cancer detection. Results: Overall, 20 of 105 patients (19%) had prostate cancer. The area under the curve (AUC) for percent free PSA density was 0.771, not significantly higher than the AUC of 0.75 for PSA density (p = 0.778), but significantly higher than the AUC of 0.604 for percent free PSA (p = 0.021). Of these three parameters, percent free PSA density yielded the highest specificity percentage (54.1%) at 95% sensitivity. Conclusions: Percent free PSA density is more specific than percent free PSA in distinguishing benign from malignant disease in men with a normal digital rectal examination and an intermediate PSA level. Further study is necessary to discover whether percent free PSA density is superior to percent free PSA or PSA density.

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