US Pharm. 2013;38(1):HS-6-HS-8.
Prostate cancer is a heterogeneous
disease that is often slow growing. However, if the cancer is advanced
or left untreated in the early stages, the cancer cells may metastasize
from the prostate to other parts of the body, particularly the bones
and lymph nodes.1 The symptoms of prostate cancer closely
resemble benign prostatic hyperplasia. These symptoms include frequent
urination, nocturia (increased urination at night), difficulty starting
and maintaining a steady stream of urine, hematuria (blood in the
urine), and dysuria (painful urination). Approximately one-third of
patients diagnosed with prostate cancer have one or more such symptoms,
while two-thirds have no symptoms.2
According to the American Cancer Society
(ACS), prostate cancer is the second most common type of cancer found
in American men and the second leading cause of cancer death in men.3
One in every 6 men will be diagnosed with prostate cancer during their
lifetime, and 1 in 36 will die from the disease. This year, more than
241,700 new cases of prostate cancer will be diagnosed.4 Studies demonstrate that African Americans are at a higher risk of developing prostate cancer.5
Once men reach age 50 years, most
physicians will order a prostate-specific antigen (PSA) level and a
digital rectal examination (DRE). However, in men who are at a higher
risk, screenings should begin at the age of 45.5
Traditionally, DRE has been recommended for the detection of prostate
cancer because of low cost, ease of performance, and safety. Though the
specificity of the DRE is ≥85%, its use as a single screening method
has minimal effect on the prevention of the disease. As such, the
combination of DRE and PSA is a better method in detecting prostate
cancer than DRE alone.5
Since the institution of serum PSA as a
screening method, much effort has been expended to optimize early
detection of prostate cancer. The normal range of PSA is ≤4 ng/mL. If
the PSA level is between 4 and 10 ng/mL, further testing involving
invasive procedures may be needed to distinguish benign prostatic
hyperplasia from prostate cancer.5 Although PSA levels
conventionally have a greater specificity for prostate enlargement than
cancer detection, each year in the United States more than one million
men undergo biopsies as a result of PSA elevations, and most of these
biopsies are negative. Additionally, repeat biopsies are ordered in
approximately 30% of patients who are suspected of having prostate
cancer.4 Controversy still exists regarding whether to repeat a prostate biopsy in patients with a previous negative biopsy.
Repeat Biopsy Concerns
Unnecessary repeat biopsies are an area of concern due to a high rate of complications and associated costs.6
Patients who undergo repeat biopsies are subject to serious
complications such as septicemia, urinary infections, bladder
perforation, reduced sexual activity, and severe pain.7
Moreover, research has demonstrated that men who undergo prostate
biopsy experience a moderate or higher level of pain and report pain
scores of 5 or more on a 0 to 10 scale.8
As of late, the PCA3 gene has proven to be a vital marker in the detection of prostate cancer.9
The PCA3 gene produces a noncoding RNA that is only expressed in human
prostate tissue and overexpressed in 95% of prostate cancer cells.10,11
Due to prostate-specific expression, PCA3 RNA is very useful as a tumor
marker and has been proven to be more accurate than traditional PSA
testing in patients who have undergone one or more previous negative
On February 13, 2012, the FDA approved
the PROGENSA PCA3 [prostate cancer gene 3] Assay—the first molecular
test to assist in determining whether a repeat biopsy is required when
used with other clinical information and laboratory data.12
The PROGENSA PCA3 Assay is approved for use in men who have had
previous negative prostate biopsies. The assay is not indicated for use
in men who have evidence of atypical small acinar proliferation on
their last biopsy.13 The PROGENSA PCA3 Assay should be
employed using the first-void urine. Once the first-void urine is
collected, a portion of the urine sample is transferred to a tube
containing urine transport medium, encouraging the lysis and
stabilization of RNA. Instructions for use are found in TABLE 1.14
Candidates for the PCA3 assay are men who have experienced one or more
previous negative biopsies and who are being considered for repeat
biopsy by a urologist.15
test utilizes the PCA3 score that is derived from the ratio of PCA3 RNA
to PSA RNA and provides the degree of probability a prostate biopsy
will result in prostate cancer. The score may range from less than 5 to
greater than 100. A PCA3 score of less than 25 is associated with a
decreased likelihood of a positive biopsy. Though the PCA3 score does
not rule out cancer, when used in conjunction with PSA, DRE, age, and
prostate size, it allows a better estimate to be made regarding the
risk of biopsy-detectable prostate cancer.16
clinical trial was conducted to show whether the PCA3 Assay was helpful
in determining prostate cancer. Inclusion criteria consisted of men
over the age of 50 years, who had one or more previous negative
biopsies and were recommended for a repeat biopsy.17 The
study excluded patients with a history of prostate cancer and patients
taking medications that might influence PSA levels. Drugs that affect
PSA levels are found in TABLE 2.
The pivotal clinical study was a
prospective, multicenter trial from 14 community-based urology clinics.
Data collected included patient age, DRE result, race, family history,
serum PSA level, and number of previous negative biopsies (TABLE 3).17
In the study, there were a total of 495 eligible patients; however, 466
patients had a valid PCA3 score and available biopsy results. Of those
patients the median age was 67 years; 77% had no family history of
prostate cancer, while 102/466 patients had a positive repeat biopsy
during the study. When testing the specificity, precision, and
sensitivity of the product, tests were conducted using female urine as
a control. The authors concluded that the test was helpful in making
informed decisions about repeat biopsies for patients. Importantly, the
negative predictive value was 90%, meaning that a PCA3 score <25
correctly predicted a negative repeat biopsy 90% of the time.17
Men should discuss with their clinician
the benefits and risks associated with prostate screenings and the need
for repeat biopsies. Once a decision has been made to move forward with
screenings, the PROGENSA PCA3 Assay is a practical choice because it
helps to minimize associated risks. More information about the PCA3
Assay may be found at www.gen-probe.com/
1. Prostate cancer introduction. Health
Accessed October 28, 2012.
2. Miller DC, Hafez KS, Stewart A, et
al. Prostate carcinoma presentation, diagnosis, and staging: an update
from the National Cancer Data Base. Cancer. 2003;98(6):1169-1178.
3. What are the key statistics about
Accessed October 31, 2012.
4. Kader K. Genetic test may reduce need
for repeat biopsy for prostate cancer.
http://health.ucsd.edu/news/releases/Pages/2012-07-17-genetic-test-may-predict-prostate-cancer.aspx. Accessed October 30, 2012.
5. DiPiro JT. Pharmacotherapy: A Pathophysiologic Approach. New York, NY: McGraw-Hill Medical; 2011.
6. Busby JE. Determining variables for
repeat prostate biopsy. Nature Publishing Group.
www.nature.com/pcan/journal/v7/n2/full/4500708a.html. Accessed October
7. Diaz G. Prostate biopsy: 18 reasons to avoid it. www.drgdiaz.com/prostate/prostatebiopsy.shtml. Accessed October 29, 2012.
8. Mayo Clinic. What causes men pain in
prostate biopsy and best method to alleviate it. Medical News Today.
MediLexicon International. www.medicalnewstoday.com/releases/52060.php.
Accessed October 25, 2012.
9. Urological Sciences Research
Foundation. PCA3: a genetic marker of prostate cancer.
www.usrf.org/news/PCA3/PCA3.html. Accessed October 30, 2012.
10. FDA approves PCA3 gene test to aid
decisions about repeat prostate biopsies.
http://labtestsonline.org/news/120323pca3. Accessed October 25, 2012.
11. PCA3 utility. PCA3.org. www.pca3.org/pro/pca3/pca3-utility-0. Accessed October 29, 2012.
12. FDA. Medical devices. PROGENSA® PCA3 Assay. www.fda.gov/MedicalDevices/
Devices/ucm294907.htm. Accessed October 21, 2012.
13. Hologic-Genprobe. www.gen-probe.com. Accessed October 21, 2012.
14. Physician Brochure for the PROGENSA
PCA3 Assay. Gen-Probe. www.gen-probe.com/pdfs/pi/L692-MKT.pdf. Accessed
October 26, 2012.
15. PCA3 Assay, prostate biopsies,
PROGENSA, prostate cancer urine test, repeat prostate biopsies,
urine-based molecular test, positive biopsy, negative biopsy, prostate
cancer diagnosis, cancerous prostate tissue, PCA3, urology, atypical
small acinar proliferation, ASAP.
www.gen-probe.com/products-services/progensa-pca3. Accessed October 24,
16. PCA3 score. www.windsorurology.co.uk/Clinical_Information/PCA3_score.aspx. Accessed October 26, 2012.
17. PROGENSA PCA3 Assay for in Vitro
Diagnostic Use. Gen-Probe.
www.gen-probe.com/pdfs/pi/502083-EN-RevB.pdf. Accessed October 28, 2012.
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