Prostate-specific antigen (PSA) is the only tumor marker
available which has been approved for use as a screening test
for cancer. It is highly specific for prostate tissue and may be
increased in prostate cancer, benign prostatic hyperplasia
(BPH) and prostatitis. Currently a cutoff of 4 ng/mL is used for
prostate cancer screening. PSA values >10 ng/mL are highly
predictive of cancer. Approximately one-third of patients with
PSA levels between 4-10 ng/mL will have prostate cancer
detectable by biopsy within one year.

There are several forms of PSA present in serum. Most of the
measurable PSA in serum is complexed with the protease
inhibitor alpha-1 antichymotrypsin (PSA-ACT). PSA is also
found in a free form, not complexed to a protease inhibitor. A
greater proportion of free PSA is found in patients with benign
conditions of the prostate than in patients with prostate cancer.
Determination of the percentage of each of the forms of
PSA may help to distinguish benign from malignant
conditions.


Percentage of Free PSA

The Free Prostate Specific Antigen Percentage test consists of
two assays that together allow
for the calculation of the free PSA percentage. The free PSA
and PSA-ACT assays are both enzyme immunoassays (EIA)
which are specific for each form of PSA in serum. The report will list
the concentration of each form and the percentage of free PSA.

The current tests for PSA which react with both free PSA and
PSA-ACT in the serum are not able to clearly distinguish BPH
from prostate cancer. This is especially true for the population
of men with PSA values between 4-10 ng/mL. Several methods
of improving the specificity of the PSA test have been
proposed, including PSA density, PSA velocity and
age-specific reference ranges. It is in the 4-10 ng/mL range
that determination of the forms of PSA may help to
distinguish those patients most likely to have cancer and
reduce the number of biopsies for the men most likely to
have BPH. The percentage of free PSA that is seen in cancer
patients is consistent across age groups, therefore, age-related
reference ranges are not necessary.

Men with prostate cancer have a lower proportion of free PSA
than men with benign conditions. As reported by Catalona et
al., a cutoff of <13.7% in men with a normal sized prostate
gland detected 90% of the cancers. Use of a higher cutoff
(<20.5%) was necessary to detect 90% of the cancers in men
with an enlarged prostate. Cuts-offs depend upon the technology used.