Percent free prostate-specific antigen: Entering a new era in the detection of prostate cancer

The introduction of prostate-specific antigen (PSA) testing into clinical medicine in 1986 revolutionized the management of patients with prostate cancer, The major limitation of this tumor marker stems from its inability to provide a clear distinction between benign prostate disease and prostate cancer, especially in patients with upper limit of normal or slightly increased PSA values, Recent research has established that PSA exists in the serum in several molecular forms, Patients with benign prostatic hyperplasia have more of the free form, whereas those with prostate cancer have more of a complexed form (PSA covalently bound to alpha(1)-antichymotrypsin). Several investigations have now confirmed that determining percent free PSA (proportion of free PSA to total PSA) enhances the ability of PSA testing to distinguish between prostate cancer and benign prostatic hyperplasia. In addition, percent free PSA seems to have the greatest clinical significance in patients whose total PSA values range from 2.5 or 3.0 ng/mL (lower limit) to 10.0 ng/mL (upper limit), When the total PSA value is in the normal range (2.5 or 3.0 to 4.0 ng/mL), percent free PSA makes PSA a more sensitive test (increases cancer detection). When the total PSA level is minimally increased (4.1 to 10.0 ng/mL), percent free PSA makes PSA a more specific test (eliminates performance of unnecessary prostate biopsies), Although further work remains, it seems that percent free PSA can substantially improve the clinical utility of the PSA test for detecting early, curable prostate cancer.