Clinical Evaluation of the PCA3 Assay in Men Requiring a Repeat Biopsy

The 2 most common methods used for prostate cancer screening are the DRE and
tests to measure total serum PSA (serum PSA test). The use of the serum PSA
test has resulted in the earlier diagnosis of prostate cancer compared to other
methods, such as the DRE. Traditionally, a biopsy is performed when the serum
PSA value is greater than 4.0 ng/mL. However, an increasing number of
physicians use a cutoff value of 2.5 ng/mL to determine if a biopsy is needed;
this cutoff is often used for younger men. Although the number of unnecessary
biopsies increases by lowering the cutoff value, the number of organconfined
cancers increases, which improves patient outcomes. Although the serum PSA test
is sensitive for detecting prostate cancer, the majority (>60%) of men with
elevated serum PSA levels will be negative for cancer because serum PSA levels
can be elevated in men with noncancerous prostate disease, such as benign
prostatic hyperplasia (BPH) or prostatitis. Patient management is unclear for
men who continue to have elevated serum PSA levels after having a negative
biopsy result because a negative biopsy result is inconclusive for the absence
of cancer. Approximately 20% of men with serum PSA levels of 4.0 ng/mL or
greater will have a positive biopsy result at follow-up due to a missed cancer
diagnosis during the previous biopsy (ie, false negative biopsy result) or due
to the development of cancer over time. However, since most men with elevated
serum PSA levels will be negative for cancer at follow-up, tests with better
specificity are needed to help guide repeat biopsy decisions and to reduce
unnecessary procedures and anxiety. PCA3 has shown promise as a diagnostic tool
in prostate cancer, particularly because PCA3 has a higher specificity than the
serum PSA test.

To determine the performance characteristics (specificity, sensitivity, and
positive and negative predictive values) of the PCA3 Assay using prostate
biopsy as the reference method in men who are scheduled for a repeat prostate
biopsy after a previous negative prostate biopsy.

A nonpivotal, prospective, multi-center clinical study will be conducted. Male
subjects who are scheduled for a repeat prostate biopsy after a previous
negative prostate biopsy will be enrolled. Once enrolled into the study, blood
and urine specimens will be collected. Blood will be tested with assays that
measure total serum PSA (serum PSA test) and free serum PSA (free PSA test). A
first-catch urine sample will be collected following a special, standardized
DRE performed by an experienced medical practitioner. The urine sample will be
processed and tested with the PCA3 Assay. Biopsies will be performed by an
experienced medical practitioner per the site*s normal procedure. Biopsy
specimens will be evaluated by pathologists at the clinical site. PCA3 Assay
results will be compared to biopsy results to determine the assay*s performance
characteristics (specificity, sensitivity, positive and negative predictive
values).

One single bloodsample (3.5 mL) will be collected from each subject. This is a
lot less than the amount of blood that is drawn at a blood donation.
Subsequently, each subject will undergo a special, standardized DRE, instead of
a normal DRE. Therafter, a first-catch urine sample will be collected. The
special, standardized DRE is harmless and is regarded as 'well tolerable'. The
extent of the burden associated with participation therefore is minimal.