Several
molecular forms of PSA are known to circulate in the blood. In most men, the majority
(60% to 90%) of circulating PSA is covalently bound to endogenous protease inhibitors.
Most clinical work investigating the use of the molecular forms of PSA for early detection
of prostate cancer has focused on the percentage of PSA found circulating in the free or
unbound form.
Numerous studies have shown that the percentage of free PSA is significantly lower in
men who have prostate cancer compared with men who do not. Recently, the US Food and
Drug Administration (FDA) approved the use of percent-free PSA for the early detection of
prostate cancer in men with PSA levels between 4 and 10 ng/mL. The multi-institution study
that characterized the clinical utility of this assay showed that a 25% free PSA cutoff
detected 95% of prostate cancers while avoiding 20% of unnecessary prostate biopsies.
Since its approval by the FDA, testing for percent-free PSA has gained widespread clinical
acceptance in the United States, specifically for patients with normal DREs who have
previously undergone prostate biopsy because they had a total PSA level within the
"diagnostic gray zone"(ie, between 4 and 10 ng/mL).
The 2004 NCCN prostate cancer screening guidelines recommend using free-PSA for man with a
worrisome PSA (4 - 10) where there is some reason to avoid the risk of a biopsy (e.g. if
the patients is on blood-thinners.) and they decsribe the following for free PSA: > 25%
no biopsy; if < 10% definite biopsy; if 10-25% discuss risks/benefits of biopsy (
