• In general, serum PSA levels increase due to physical changes to prostate architecture caused by trauma, infection, inflammation, prostate manipulation, benign prostatic hypertrophy (BPH) or malignancy.3,4 The sensitivity of PSA levels to these changes serves as the basis for the clinical use of the test. The PSA concentration in the serum of healthy men is a millionfold lower than that in seminal fluid. PSA in seminal fluid is predominantly free or uncomplexed. In serum, the majority of PSA is bound to inhibitors including 1-antichymotrypsin (ACT) and -2-macroglobulin (A2M). Measured total PSA consists of free and ACT-bound since PSA complexed to A2M is not immunologically detectable.

• Catalona and coworkers found that one in four patients with normal DRE and PSA levels between 4.0 and 10.0 ng/mL have prostate cancer. They recommended using a cutoff of 25% free PSA for this group of men to identify individuals with an increased risk of prostate cancer. They found that 95% of the men with cancer (as determined by biopsy) with normal DRE and total PSA between 4 and 10 ng/mL had percent free PSA 25%. Their study further indicated that 20% of men with benign disease (as determined by biopsy) with normal DRE and a total PSA between 4 and 10 ng/mL had percent free PSA greater than the 25% cutoff.

• Alternatively, percent free PSA may be used to determine the relative risk of prostate cancer in individual men.

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