Prostate Cancer Screening (PDQ®): Screening - Health Professional Information [NCI] - Evidence of Benefit
Summary of First Four Prostate, Lung, Colorectal, and Ovarian Screening Roundsa continued...
A number of authors have considered whether complexed PSA or percent-free PSA in conjunction with total PSA can improve the latter's sensitivity. Of special interest is the gray zone of total PSA, the range from 2.5 ng/mL to 4.0 ng/mL. A meta-analysis of 18 studies addressed the added diagnostic benefit of percent-free PSA. There was no uniformity of cutoff among these studies. For cutoffs ranging from 8% to 25% (free/total), sensitivity/specificity ranged from about 45%/95% to 95%/15%.
Percent-free PSA may be related to biologic activity of the tumor. One study compared the percent-free PSA with the pathologic features of prostate cancer among 108 men with clinically localized disease who ultimately underwent radical prostatectomy. Lower percent-free PSA values were associated with higher risk of extracapsular disease and greater capsular volume. Similar findings were reported in another large series.
The third-generation (ultrasensitive) PSA test is an enzyme immunometric assay intended strictly (or solely) as an aid in the management of prostate cancer patients. The clinical usefulness of this assay as a diagnostic or screening test is unproven.[61,62]
Because larger prostates caused by increased amounts of transition-zone hyperplasia are known to be associated with higher serum PSA levels, reports have suggested indexing PSA to gland volume, using a measure known as PSA density. PSA density is defined as serum PSA divided by gland volume. Generally, ultrasound is used to measure gland volume. While early studies suggested that this measure may discriminate between patients with cancer and those with benign disease, subsequent evaluations have failed to confirm any clinically useful association.[64,65]
PSA density of the transition zone
PSA density of the transition zone (serum PSA divided by the volume of the transition zone) has been suggested to better adjust for benign sources of PSA. One study prospectively evaluated 559 men with PSA levels between 4.0 ng/mL and 10.0 ng/mL. A total of 217 of these men were ultimately found to have prostate cancer; of all PSA variants analyzed, percent-free PSA and PSA density of the transition zone were found to have the best predictive value (area under the receiver operator curve values of 0.78 and 0.83). Another study also found that PSA density of the transition zone had superior performance characteristics. In this study of 308 volunteers undergoing first-time screening, it was reported that the combination of percent-free PSA (<20%) and PSA density of the transition zone resulted in elimination of 54.2% of biopsies that ultimately proved to be benign.