Guide toYour

PSA Test
Special

Report
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Special
Report

Guide to Your PSA Test

Table of Contents

Getting a PSA Test for Prostate Cancer...................................................... 1

PSA Testing: Benefits and Caveats......................................................... 1

What Should You Do?............................................................................. 2

Improving PSA Accuracy........................................................................ 2

Beyond the PSA Test......................................................................................... 3

PSA Problems......................................................................................... 3

New Risk Prediction Tools..................................................................... 4

New Biomarkers..................................................................................... 4

More Expert Health Advice from Johns Hopkins.......................................... 6

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Getting a PSA Test for Prostate Cancer

he prostate-specific antigen (PSA) test

measures an enzyme produced almost
exclusively by the glandular cells of the
prostate. It is secreted during ejaculation into
the prostatic ducts that empty into the urethra.
A blood test to measure levels of PSA was first
approved by the U.S. Food and Drug Administration (FDA) in 1986 as a way to determine
whether prostate cancer had been treated
successfully and to monitor for its recurrence.
Today, however, PSA tests are FDA approved
for prostate cancer detection and are widely
used to screen men for the disease.
PSA Testing: Benefits and Caveats
Clinical studies, including a randomized trial known as the European
Study of Screening for Prostate Cancer (ESRPC), have shown that PSA
testing saves lives by detecting and
treating prostate cancer earlier. In
the most recent results from this trial,
prostate cancer deaths were reduced
by approximately 40 percent among
men who were screened with the PSA
test compared with those who were not
screened. This reduction in prostate
cancer deaths is similar to the decline
in prostate cancer deaths seen in the
United States since the onset of widespread PSA testing in the late 1980s.
Clinical studies to date have demonstrated the following benefits of PSA
testing:
1. An elevated PSA is the single best
predictor of the presence of prostate
cancer.

2. PSA testing detects prostate cancer about

five to 10 years earlier than digital rectal
exams.
3. Most cancers detected with PSA testing are
curable.
4. Regularly scheduled PSA testing virtually
eliminates the diagnosis of advanced prostate
cancer.
5. A baseline PSA prior to age 50 can help predict the risk of prostate cancer up to 25 years
later.
Because some of the cancers detected by
PSA screening are so small or slow growing that
they might never become life threatening, the
tradeoff of routine screening is the over diagnosis
seminal
vesicle

bladder

penis

urethra

rectum

prostate

testicle

ejaculatory
duct

Normal Male Anatomy

The prostate is a gland the size and shape of a crab apple that surrounds the upper portion
of the male urethra. Its main function is to produce part of the fluid that makes up semen.

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of non-life-threatening cancers for which treatment is not necessary. This occurs more often in
older men, who have less to gain from screening
because of a shorter life expectancy.
Another drawback of PSA testing is that most
men with an elevated PSA do not have prostate
cancer. Instead, prostate enlargement (BPH) or
inflammation is to blame. Men should discuss
both the benefits and limitations of PSA testing with their physician before having their PSA
levels measured in order to avoid unnecessary
diagnostic tests and treatments, as well as undue
anxiety.
There is no PSA level below which physicians
can reassure a man that he does not have prostate cancer. Therefore, it is not possible to define
a normal level. In men in their 40s or men
without prostate enlargement, PSA levels above
2.5 ng/mL can signal trouble. For older men,
levels above 3 to 4 ng/mL usually indicate the
need for a prostate biopsy. Most experts agree
that PSA should be used in conjunction with
other information (for example, family history,
race and age) to assess the overall likelihood that
prostate cancer is present after a discussion with
the patient about the benefits and risks.
What Should You Do?
The American Cancer Society and the American Urological Association recommend that
PSA testing and digital rectal exam (DRE) be
offered beginning at age 50. Men at increased
risk for prostate cancerblack men and men
with a family history of prostate cancershould
be offered PSA and DRE beginning at age 40
or 45. Previously, both organizations recommended annual testing for men who chose to be
screened. However, the American Cancer Society now recommends screening every two years
for men with a PSA level below 2.5 ng/mL.
The U.S. Preventive Services Task Force, an
organization that makes recommendations about

periodic health examinations) recommends that

men age 75 and older not undergo screening for
prostate cancer and contends that the current
evidence is insufficient to assess the balance of
benefits and harms of prostate cancer screening
in men younger than age 75.
One recent study found that testing all men
at age 40, age 45 and then every other year after
age 50 might be a better strategy, saving more
lives and being less expensive than other screening schedules. Other studies have concluded
that men age 50 and older who have PSA levels
below 2 ng/mL do not need to be tested every
year. However, the testing schedule should be
more frequent if a mans PSA is rising but has
not reached a threshold level where a biopsy
would be recommended.
Improving PSA Accuracy
Several factors may affect the results of a PSA
test. For example, some studies show that ejaculation one or two days before a PSA test may
increase PSA levels in the blood. Consequently,
men should abstain from sex for 72 hours prior
to a PSA test.
Digital rectal exams and biopsies of the prostate may also affect PSA levels, although the
increase in PSA caused by a digital rectal exam
is not believed to be significant enough to produce a false-positive test result in most men. A
prostate biopsy, however, may elevate PSA levels
for as long as four weeks.
Other prostate problems (such as BPH or
prostatitis) also can inflate PSA levels, and
5-alpha-reductase inhibitors for BPH treatment
(Proscar and Avodart) can lower PSA levels by
about 50 percent. When men who are taking
5-alpha-reductase inhibitors have a PSA test,
this drug-related reduction in PSA level must be
taken into account to avoid misinterpretation of
the test result.

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Beyond the PSA Test

New strategies to help doctors and patients make
more informed treatment decisions

f you have just had a prostate-specific

antigen (PSA) screening test, the words
Your PSA level is 4, are not particularly
welcome. In general, the higher the PSA, the
greater the likelihood cancer is present. So,
a score of 4 ng/mL is likely to sound warning bells for your doctor to order a biopsy, the
results of which are used to help confirm or
rule out the presence of cancer. And, if cancer
is identified, the biopsy results are also used
to help decide whether immediate or delayed
treatment is the best course of action.
Today, however, a number of prostate cancer
experts argue that a PSA level of 4 is not the
best cut-off point for triggering a biopsy. But
given recent evidence showing that most cancers identified by PSA screening are not life
threatening, it might surprise you to learn that
the new threshold is even lower.
Whats more, a growing number of doctors
are questioning the value of using any single
PSA value for all men. Instead, they consider
the PSA result as just one of many pieces of
information that can be used to help determine a mans risk of having prostate cancer
that needs treatment.
PSA Problems
Experts worry that a PSA screening cutoff of 4
ng/mL is not sufficiently sensitive. The term

sensitivity describes how good a test is at not

missing people who have a conditionin this
case, prostate cancer. This is referred to as a
false negative.
In the Prostate Cancer Prevention Trial, for
example, 7 percent of men who had a PSA level
of below 0.5 ng/mL had cancer, and about
12 percent of those cancers were high-grade,
aggressive tumors with the potential to become
life threatening; among men with a PSA of 3.1
to 4 ng/mL, 27 percent had cancer, and 25
percent of those were high grade.
As a result of findings from this and other
studies, many doctors now recommend lowering the threshold for a standard biopsy from
4 ng/mL to 2.6 ng/mL to pick up some of
the men who were missed by using the higher
threshold.
Of course, while lowering the threshold allows
for the identification of more men with prostate
cancer, it also means that even more men who
dont have cancer or who have non-life-threatening disease will be flagged. Those with cancer
may be subjected to medical procedures they
may not need, especially if they are older and
have other medical problemsa concern that
has prompted doctors to rethink their advice
about who needs regular screening.
There also is the tests specificity to consider.
This term refers to how good a test is at not

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accidentally labeling people who dont have a
condition, such as prostate cancer, as having
it. This is referred to as a false-positive result.
Many factors, such as benign prostatic hyperplasia (BPH), prostatic inflammation or even
an ejaculation within 72 hours of a PSA test,
can cause a false-positive result.
One answer to these dilemmas may be to
combine the PSA test results with additional
information from other sources to more accurately diagnose prostate cancer and predict the
risk of disease progression.
New Risk Prediction Tools
One method of predicting risk that is gaining
popularity is the use of nomograms. A nomogram considers multiple weighted factors to calculate risk. For example, a nomogram that was
developed using information from the Prostate
Cancer Prevention Trial attempts to determine
your risk of having biopsy-detectable prostate
cancer based on information about your race,
age, PSA level, family history of prostate cancer, digital rectal examination (DRE) results,
whether youve had a biopsy in the past and
whether you take finasteride (Proscar).
Other nomograms that have been developed
can calculate outcomes such as the chances
that your disease will not progress if you choose
a particular treatment or the probability of survival if you have a radical prostatectomy.
Its important to realize that the information
obtained from a nomogram is simply a prediction based on population data, much like the
insurance industry predicts longevity based on
age, medical history and other factors. While
such information can help patients in making
decisions, its not a guarantee of a particular
outcome nor is it a substitute for your doctors
clinical judgment.

New Biomarkers
Biomarkers are substances like PSA that can
be measured in blood, urine or other body fluids and used to detect or monitor a disease.
Researchers are investigating a number of
potential biomarkers that, in the future, may
improve upon the PSA tests ability to detect
prostate cancer and identify potentially lifethreatening tumors. Two promising biomarkers are PCA3 and gene fusions.
PCA3. PCA3 is a test that measures a gene
that is overexpressed (60 to 100 times greater)
in prostate cancer cells versus noncancerous
cells. Cells shed by the prostate containing the
PCA3 gene are detectable in the urine.
Researchers report that the lower the level of
PCA3 in the urine, the less likely prostate cancer is present. Because PCA3 is not produced
or is produced only minimally by noncancerous cells, the presence of conditions like BPH
or infection is less likely to produce falsely elevated PCA3 levels.
PCA3 testing is most reliable when done in
conjunction with a DRE. Researchers report
that when performed after a DRE, the results
from PCA3 testing are valid in 98 percent of
the cases. If the test is performed without a
DRE, validity drops to 80 percent.
Rather than replacing PSA screening,
researchers believe that the PCA3 test may help
identify or rule out cancer in men with elevated
PSA levels but no cancer on the initial biopsy.
In addition, some evidence suggests that the
test may be useful in helping to identify men
who are appropriate candidates for active surveillance. Currently, in the United States PCA3
testing is available only through clinical trials.
Gene Fusions. A gene fusion is a hybrid
gene formed from two previously separated
genes. Scientists have discovered that many
prostate cancer patients have gene fusions

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involving the ERG and TMPRSS2 genes that

create a new gene that is thought to promote
the development of prostate cancerand, possibly, a more aggressive form of the disease.
Gene fusions are now being detected in urine
and have promise as new biomarkers for prostate cancer. More research is needed, however,
before this method of testing moves into the
mainstream.

In the Meantime
Regular PSA screening still plays a valuable
role for many men. If your doctor recommends
regular screening, keep track of your PSA levels and monitor the trends over time. This can
help you and your doctor identify trouble signs
in the earliest stages. A sign that prostate cancer may be present is a continuously rising PSA
even if your absolute PSA score is in the normal range.

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Rely on Expert Health Advice From Johns Hopkins
Consistently ranked Americas #1 Hospital by U.S. News & World Report
N

EW

The Johns Hopkins White Papers

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Prostate Disorders
H. Ballentine Carter, M.D.

T h e Ye a rs L aTe s T r e s e a rc h
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The first prostate cancer

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This all-in-one comprehensive guide explains everything you need to know about your prostatewhat it is, what it does, and what problems can develop, such as prostatitis, benign
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Proven methods to boost bone strength
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The Johns Hopkins Prostate Disorders Bulletin

Written by Dr. Jacek L. Mostwin and his esteemed colleagues at the

world-renowned James Buchanan Brady Urological Institute, the Johns
Hopkins Prostate Disorders Bulletin is an indispensable quarterly journal
for men with prostate cancer. It also covers other prostate health problems, including benign prostatic hyperplasia (BPH) and prostatitis, and related concerns such
as overactive bladder and erectile dysfunction. With in-depth reports from leading experts and
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Choosing The RighT TReaTmenT FoR PRosTaTe CanCeR

Choosing the
Right
Treatment for

Prostate
Cancer

Choosing the Right Treatment for Prostate Cancer

This comprehensive report is a must-read for any man recently diagnosed

with prostate cancer who is looking for answers to pressing questions about treatment
options. Written by specialists at Americas #1 urology center, it takes you step-by-step
through the decision-making process to help you make informed choices. Our experts explain:
proactive surveillance, also known as expectant management ... nerve-sparing radical prostatectomy . . . radiation therapy, including EBRT, 3DCRT, IMRT, IGT and brachytherapy.

Advanced Prostate Cancer Treatments: Know Your

Options When Your Cancer Comes Back

For anyone who has had a recurrence of prostate cancer, this 113-page
report features detailed discussions with leading experts at Johns Hopkins on the treatment options currently available. You will learn about established therapies
as well as new approaches being developed at Johns Hopkins and at other important medical
centers. These treatments include gene therapy to stop the advance of the disease, monoclonal antibodies that zap cancer cells throughout the body, and a variety of chemotherapy
agents such as Taxotere and angiogenesis inhibitors (drugs that choke off the blood supply
to tumors).

Advanced
Prostate
Cancer
Treatments

Know Your Options When Your

Cancer Comes Back

For more information, or to order, go to:

JohnsHopkinsHealthAlerts.com/bookstore
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The information contained in this Special Report is not intended as a substitute for the
advice of a physician. Readers who suspect they may have specific medical problems
should consult a physician about any suggestions made.
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