A remarkable increase in the incidence of prostate cancer was observed in the United
States in the 1990s. This observation can be attributed to the widespread use of PSA
testing. From 1984 to 1994, the use of PSA testing for diagnostic purposes increased
dramatically and the percent of cancers diagnosed due to PSA increased from 5.1% to
60.6% over this period of time. More importantly, the vast majority of these cancers
were diagnosed at an early stage when most treatment options are available to the
patient. Additionally, most of these cancers diagnosed with PSA are clinically
Prostate specific antigen (PSA) is a protein that is almost exclusively produced by the
prostate gland. This unique attribute has allowed medical professionals to utilize it for
the detection of prostate cancer which is the most common cancer men will be
diagnosed with in their lifetime and the second most common cause of cancer death.
In 2004, there was an estimated 230,000 men diagnosed with prostate cancer and over
30,000 deaths from this disease. Large population screening studies have shown
that the best way to increase the detection of prostate cancer while it is still at a curable
stage is to use PSA as an initial screening test.
Prior to the discovery of PSA, physicians almost exclusively relied on digital rectal
examination (DRE) for diagnosing prostate cancer. Many men presented at that time
with advanced or incurable disease. Over the last ten years we have seen a significant
drop in the incidence of patients presenting with metastatic disease and this has been
linked directly to the widespresd use of PSA. DRE alone will miss up to 45% of cancers
while PSA alone will only miss 18% of cancers in one large multicenter screening
study. Thus, utilizing PSA with DRE for screening will improve cancer detection to 81%
over DRE alone giving us an overall detection rate of 82%.
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The normal level for PSA is less than 4 ng/ml. There are multiple reasons why your
PSA can become elevated. Enlargement of the prostate gland (BPH), infection, prostate
cancer, recent ejaculation, placement of a urinary catheter, prostate biopsy or
instrumentation of the urinary system can all cause elevation of your PSA. Contrary to
popular belief, DRE does not cause your PSA to become elevated to any clinically
The percentage of elevated PSA in the range of 4-10 ng/ml that is attributed to prostate
cancer is only 31.5%. This number rises to greater than 50% when we only consider
those patients with a PSA above 10 ng/ml. This means that the majority of cases of an
elevated PSA can be attributed to benign causes, mainly BPH. This is why we need to
biopsy many men who will never have prostate cancer to better detect this subset of
men with the disease. However, the advantage of this established biopsy criteria is that
88% of cancers that are diagnosed with a PSA less than 10 ng/ml will have disease
confined to the prostate.
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The American Urological Association (AUA) has established guidelines for prostate
cancer screening. Every man who is 50 years old should undergo prostate cancer
screening with a PSA and DRE on an annual basis. If the patient is African-American or
has a first degree relative diagnosed at an early age with prostate cancer, then they
should start screening at the age of 40. This can be performed by the patientís primary
care physician or an urologist. Screening should continue until the age of 72 or as long
as the patient has a greater than 10 year life expectancy. The rationale for this has
been that prostate cancer is a slow growing cancer and that only younger patients or
those with a greater than 10 year life expectancy will benefit from treatment. Patients
who have undergone a prior vasectomy are NOT at any increased risk of developing
prostate cancer and therefore should only follow the above guidelines.
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There are a variety of commercially available PSA screening tests available. These
tests use 4.0 ng/ml as a cutoff for a normal value. The sensitivity of these tests starts at
0.1 ng/ml. Most men with a prostate will have a PSA somewhere in this range. A
ďsuper sensitiveĒ PSA test is also available and can detect changes in PSA at a much
lower level, however, this test is only useful after radical prostatectomy to detect early
recurrences. A total PSA test is the only test currently recommended for screening for
prostate cancer. However, because an elevated PSA between 4-10 ng/ml is only
predictive of cancer in approximately 30% of patients, a more precise way of looking at
PSA is needed. Urologists have developed several useful ways to make PSA more
helpful for detecting cancer.
PSA velocity is a useful measurement for differentiating benign from malignant
elevations of PSA. Three measurements, over a two year period obtained from the
same lab can be used to determine PSA velocity. A rise of greater than 0.75 ng/ml/year
is suggestive of cancer while lower rises suggest benign disease.
Another useful way of evaluating PSA is by using age-specific reference values. By
lowering the threshold for younger men and raising it for older ones to account for
natural enlargement of the prostate, we can eliminate unnecessary biopsies. PSA
normally increases by 4% per ml of prostate tissue as it enlarges with aging. Applying
age specific references makes the test more sensitive for younger patients and more
specific for older ones. For a man 40-49 years a value of 0-2.5, 50-59 years a value 0-
3.5, 60-69 years a value of 0-4.5 and for 70-79 years a value of 0-6.5 ng/ml is
Although not considered a primary screening test for prostate cancer, a percent free
PSA (fPSA) has become a very useful test when considering whether to biopsy a
patient with an elevated PSA in the 4-10 ng/ml range. A percent fraction of fPSA less
than 25% has been shown to correlate with prostate cancer better than total PSA. It has
been shown that we can improve the specificity of PSA in this range, reducing the
number of unnecessary biopsies by 20% while still mainting a 95% sensitivity for
prostate cancer detection. However, the utility of fPSA in the less than 4.0 ng/ml
range has not been shown to be helpful and until more conclusive evidence presents
this practice should be discouraged.
There are several other cancer detection markers on the horizon that may prove to be
beneficial for decreasing the number of unnecessary biopsies while still maintaining
the same degree of sensitivity for detecting prostate cancer. However, most of these
tests are still experimental or awaiting approval for the screening of prostate
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We now know from the recent Prostate Cancer Prevention Trial (PCPT) that
approximately 25% of men with a PSA in the range 2.1-4.0 ng/ml will be found to have
prostate cancer. Twenty one percent of these cancers are considered high grade
supporting the fact that these are clinically significant tumors. Another study found that
14% of men with an abnormal DRE and a PSA 2.5-4.0 ng/ml had prostate cancer,
supporting the idea that men with really low PSAs can still have cancer. Based on this
information some urologists are justifying proceeding with prostate biopsy when the
PSA is above 2.5 ng/ml.
Another scenario in which a biopsy is warranted with a low PSA is in the patient taking a
5-alpha-reductase inhibitor (finasteride, dutasteride) for prostate enlargement. These
medicines are well known for artificially lowering a manís PSA by 50% after taking the
medicine for 6 months. Therefore a man on one of these medicines with a PSA of 3.0
should really be considered as having a PSA of 6.0 and referred for biopsy.
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There is very little preparation prior to obtaining a PSA test. Patients should refrain from
ejaculation for at least a 24 hour period. PSA tests should be avoided in the setting of
acute infection of the urine or prostate as this may lead to a false positive result.
Urinalysis should be obtained prior to performing a PSA test if infection is suspected.
Testing should wait until the infection has been adequately treated with antibiotics.
PSA testing should be avoided in the setting of an indwelling urethral catheter or within
6 weeks of an episode of acute urinary retention.
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The level of PSA found in the manís blood is one of the most reliable predictors of
whether or not there is prostate cancer. A physician can utilize PSA in different ways to
screen for this disease and decide with the patient when is the appropriate time for
prostate biopsy. Once the diagnosis of prostate cancer is made, PSA can help the
physician guide patients to the most appropriate therapy and coupled with the
pathologic grade from the biopsy, offer the patient a prognosis. After treatment, PSA is
essential for monitoring the effectiveness of therapy and surveillance for recurrence.
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1. Jemal, A., et al., Cancer statistics, 2004. CA Cancer J Clin, 2004. 54(1): p. 8-29.
2. Bartsch, G., et al., Prostate cancer mortality after introduction of prostate-specific
antigen mass screening in the Federal State of Tyrol, Austria. Urology, 2001. 58(3): p.
3. Catalona, W.J., et al., Comparison of digital rectal examination and serum prostate
specific antigen in the early detection of prostate cancer: results of a multicenter clinical
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4. Effect of digital rectal examination on serum prostate-specific antigen in a primary
care setting. The Internal Medicine Clinic Research Consortium. Arch Intern Med, 1995.
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5. Andriole, G.L., et al., Prostate Cancer Screening in the Prostate, Lung, Colorectal
and Ovarian (PLCO) Cancer Screening Trial: findings from the initial screening round of
a randomized trial. J Natl Cancer Inst, 2005. 97(6): p. 433-8.
6. Cox, B., et al., Vasectomy and risk of prostate cancer. Jama, 2002. 287(23): p.
7. Oesterling, J.E., et al., Serum prostate-specific antigen in a community-based
population of healthy men. Establishment of age-specific reference ranges. Jama,
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8. Catalona, W.J., et al., Use of the percentage of free prostate-specific antigen to
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specific antigen level or =4.0 ng per milliliter. N Engl J Med, 2004. 350(22): p. 2239-46.
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