Clinical utility of measurements of free and total prostate-specific antigen (PSA): A review

BACKGROUND. Prostate-specific antigen (PSA) is a widely-used tumor marker to aid in the early detection of prostate cancer. PSA testing has appreciable false-positive and false-negative results, particularly in the 2.5-10.0 ng/ml range. Measurements of the percentage of nonprotein-bound (free) PSA in serum, which is lower in patients with prostate cancer, has been evaluated as a method for increasing the accuracy of PSA testing. METHODS. The literature on forms of PSA in serum, as it relates to issues of clinical utility for prostate cancer screening, was reviewed and summarized through May 1996. RESULTS. Measurements of the percentage of free PSA in serum increases the accuracy of PSA testing for prostate cancer in men whose total PSA levels are 2.5-10.0 ng/ml. Cutoffs for screening are affected by prostate volume and total PSA levels. One study also demonstrated a correlation between percentage of free PSA and pathologic features of cancer aggressiveness. CONCLUSIONS. Measurement of free PSA in serum has potential clinical utility for increasing the sensitivity and specificity of PSA screening. Insufficient data are available to establish cutoffs to be used in clinical practice. Cutoffs are affected by total PSA level and prostate volume. The prevalence rate of cancer in the screened population (age, race, previous biopsy history, etc.) will also influence screening cutoffs. Percentage of free PSA may also correlate with the potential aggressiveness of early-stage prostate cancer.