Prostate-specific antigen: update 1997

Prostate-specific antigen (PSA) is the most important tumor marker for prostate cancer, although it is not a perfect marker as it is not cancer-specific. PSA, a member of the human kallikrein family, is present in two molecular forms in serum: free and complexed to protease inhibitors. PSA is now commonly measured on automated immunoassay systems employing monoclonal or polyclonal antibodies. Results from different assays can vary since some assays are not equimolar and react to the free and complexed forms differently. Utilization of the molecular forms of PSA is one approach to improve the sensitivity and specificity of the PSA assay. Patients with prostate cancer have a greater percentage of PSA bound to alpha1-antichymotripsin (ACT) than those without cancer. Measurement of the free to total PSA ratio in the diagnostic gray zone (usually 4-10 micrograms/liter of total PSA), where prostate cancer and benign prostatic hyperplasia (BPH) overlap, has been shown to eliminate between 16 and 79% of unnecessary biopsies. Free to total PSA cutoffs are influenced by the sensitivity and specificity values chosen, the reflex range for total PSA used, differences in free PSA assays, differences in populations studied, and factors such as total PSA concentrations, age, and prostate gland size. In addition to the molecular forms of PSA, age-specific reference ranges, rate of change of PSA concentrations (PSA velocity), ratio of serum PSA to prostate volume (PSA density), and neural network derived indices have been employed to improve the clinical utility of PSA measurements.