What is the
prostate-specific antigen (PSA) test?
Prostate-specific antigen (PSA) is a protein produced by the cells of the
prostate gland. The PSA test measures the level of PSA in the blood. The doctor
takes a blood sample, and the amount of PSA is measured in a laboratory. Because
PSA is produced by the body and can be used to detect disease, it is sometimes
called a biological marker or tumor marker.
It is normal for men to have low levels of PSA in their blood; however, prostate
cancer or benign (not cancerous) conditions can increase PSA levels. As men age,
both benign prostate conditions and prostate cancer become more frequent. The
most common benign prostate conditions are prostatitis (inflammation of the
prostate) and benign prostatic hyperplasia (BPH) (enlargement of the prostate).
There is no evidence that prostatitis or BPH causes cancer, but it is possible
for a man to have one or both of these conditions and to develop prostate cancer
as well.
PSA levels alone do not give doctors enough information to distinguish between
benign prostate conditions and cancer. However, the doctor will take the result
of the PSA test into account when deciding whether to check further for signs of
prostate cancer.
Why is the PSA test performed?
The U.S. Food and Drug Administration (FDA) has approved the PSA test along with
a digital rectal exam (DRE) to help detect prostate cancer in men age 50 and
older. During a DRE, a doctor inserts a gloved finger into the rectum and feels
the prostate gland through the rectal wall to check for bumps or abnormal areas.
Doctors often use the PSA test and DRE as prostate cancer screening tests;
together, these tests can help doctors detect prostate cancer in men who have no
symptoms of the disease.
The FDA has also approved the PSA test to monitor patients with a history of
prostate cancer to see if the cancer has recurred (come back). If the PSA level
begins to rise, it may be the first sign of recurrence. Such a biochemical
relapse typically precedes clinical relapse by months or years. However, a
single elevated PSA level in a patient with a history of prostate cancer does
not always mean the cancer has come back. A man who has been treated for
prostate cancer should discuss an elevated PSA level with his doctor. The doctor
may recommend repeating the PSA test or performing other tests to check for
evidence of recurrence. The doctor may look for a trend of rising PSAs over time
rather than a single elevated PSA.
It is important to note that a man who is receiving hormone therapy for prostate
cancer may have a low PSA reading during, or immediately after, treatment. The
low level may not be a true measure of PSA activity in the man’s body. Men
receiving hormone therapy should talk with their doctor, who may advise them to
wait a few months after hormone treatment before having a PSA test.
For whom might a PSA screening test be
recommended?
Doctors’ recommendations for screening vary. Some encourage yearly screening for
men over age 50, and some advise men who are at a higher risk for prostate
cancer to begin screening at age 40 or 45. Others caution against routine
screening, while still others counsel men about the risks and benefits on an
individual basis and encourage men to make personal decisions about screening.
Currently, Medicare provides coverage for an annual PSA test for all men age 50
and older.
Several risk factors increase a man’s chances of developing prostate cancer.
These factors may be taken into consideration when a doctor recommends
screening. Age is the most common risk factor, with nearly 65 percent of
prostate cancer cases occurring in men age 65 and older (1). Other risk factors
for prostate cancer include family history, race, and possibly diet. Men who
have a father or brother with prostate cancer have a greater chance of
developing prostate cancer. African American men have the highest rate of
prostate cancer, while Asian and Native American men have the lowest rates. In
addition, there is some evidence that a diet higher in fat, especially animal
fat, may increase the risk of prostate cancer.
How are PSA test results reported?
PSA test results report the level of PSA detected in the blood. The test results
are usually reported as nanograms of PSA per milliliter (ng/mL) of blood. In the
past, most doctors considered PSA values below 4.0 ng/mL as normal. However,
recent research found prostate cancer in men with PSA levels below 4.0 ng/mL
(2). Many doctors are now using the following ranges with some variation:
* 0 to 2.5 ng/mL is low.
* 2.6 to 10 ng/mL is slightly to moderately elevated.
* 10 to 19.9 ng/mL is moderately elevated.
* 20 ng/mL or more is significantly elevated.
There is no specific normal or abnormal PSA level. The higher a man’s PSA level,
the more likely it is that cancer is present. But because various factors (such
as age) can cause PSA levels to fluctuate, one abnormal PSA test does not
necessarily indicate a need for other diagnostic tests. When PSA levels continue
to rise over time, other tests may be needed.
It should be noted that it is common for normal PSA ranges to vary somewhat from
laboratory to laboratory.
What if the screening test results show
an elevated PSA level?
A man should discuss elevated PSA test results with his doctor. There can be
different reasons for an elevated PSA level, including prostate cancer, benign
prostate enlargement, inflammation, infection, age, and race.
If no other symptoms suggest cancer, the doctor may recommend repeating DRE and
PSA tests regularly to watch for any changes. If a man’s PSA levels have been
increasing or if a suspicious lump is detected during the DRE, the doctor may
recommend other tests to determine if there is cancer or another problem in the
prostate. A urine test may be used to detect a urinary tract infection or blood
in the urine. The doctor may recommend imaging tests, such as ultrasound (a test
in which high-frequency sound waves are used to obtain images of the kidneys and
bladder), x-rays, or cystoscopy (a procedure in which a doctor looks into the
urethra and bladder through a thin, lighted tube). Medicine or surgery may be
recommended if the problem is BPH or an infection.
If cancer is suspected, a biopsy is needed to determine if cancer is present in
the prostate. During a biopsy, samples of prostate tissue are removed, usually
with a needle, and viewed under a microscope. The doctor may use ultrasound to
view the prostate during the biopsy, but ultrasound cannot be used alone to tell
if cancer is present
# What if the test results show a rising PSA level after treatment for prostate
cancer?
A man should discuss rising PSA test levels with his doctor. Doctors consider a
number of factors before recommending further treatment. Additional treatment
based on a single PSA test result is often not recommended. Rather, a rising
trend in PSA test results over a period of time combined with other findings,
such as an abnormal DRE, positive prostate biopsy results, or abnormal CT
(computed tomography) scan results, may lead to a recommendation for further
treatment.
According to the National Comprehensive Cancer Network (NCCN) Clinical Practice
Guidelines in Oncology for Prostate Cancer (3), additional treatment may be
indicated based on the following PSA test results:
* For men who have been in the watchful waiting phase—PSA levels have doubled in
fewer than 3 years or PSA velocity (change in PSA levels over time) is greater
than 0.75 ng/mL, in addition to a prostate biopsy showing evidence of worsening
cancer (3).
* For men who have had a radical prostatectomy (removal of the prostate gland)—PSA
does not fall to undetectable levels after surgery or a detectable PSA (> 0.3 ng/mL)
that increases on two or more subsequent measurements after having undetectable
levels (3).
* For men who have had other initial therapy, such as radiation therapy and/or
hormonal therapy—PSA levels have risen three consecutive times at least 3 months
apart after having reached an undetectable or very low level (3).
Please note that these are general guidelines. Prostate cancer is a complex
disease and many variables need to be considered by each patient and his doctor.
What are some of the limitations of the PSA test?
* Detection does not always mean saving lives: When used in screening, the PSA
test can detect small tumors. However, finding a small tumor does not
necessarily reduce a man’s chance of dying from prostate cancer. PSA testing may
identify very slow-growing tumors that are unlikely to threaten a man’s life.
Also, PSA testing may not help a man with a fast-growing or aggressive cancer
that has already spread to other parts of his body before being detected.
* False positive tests: False positive test results (also called false
positives) occur when the PSA level is elevated but no cancer is actually
present. False positives may lead to additional medical procedures that have
potential risks and significant financial costs and can create anxiety for the
patient and his family. Most men with an elevated PSA test turn out not to have
cancer; only 25 to 30 percent of men who have a biopsy due to elevated PSA
levels actually have prostate cancer (4).
* False negative tests: False negative test results (also called false
negatives) occur when the PSA level is in the normal range even though prostate
cancer is actually present. Most prostate cancers are slow-growing and may exist
for decades before they are large enough to cause symptoms. Subsequent PSA tests
may indicate a problem before the disease progresses significantly.
Why is the PSA test controversial in screening?
Using the PSA test to screen men for prostate cancer is controversial because it
is not yet known if this test actually saves lives. Moreover, it is not clear if
the benefits of PSA screening outweigh the risks of follow-up diagnostic tests
and cancer treatments. For example, the PSA test may detect small cancers that
would never become life threatening. This situation, called overdiagnosis, puts
men at risk for complications from unnecessary treatment such as surgery or
radiation.
The procedure used to diagnose prostate cancer (prostate biopsy) may cause side
effects, including bleeding and infection. Prostate cancer treatment may cause
incontinence (inability to control urine flow) and erectile dysfunction
(erections inadequate for intercourse). For these reasons, it is important that
the benefits and risks of diagnostic procedures and treatment be taken into
account when considering whether to undertake prostate cancer screening.
What research is being done to validate
and improve the PSA test?
The benefits of screening for prostate cancer are still being studied. The
National Cancer Institute (NCI), a component of the National Institutes of
Health, is currently conducting the Prostate, Lung, Colorectal, and Ovarian
Cancer Screening Trial, or PLCO trial, to determine if certain screening tests
reduce the number of deaths from these cancers. The DRE and PSA are being
studied to determine whether yearly screening to detect prostate cancer will
decrease a man’s chance of dying from prostate cancer. Full results from this
study are expected in several years.
Scientists also are researching ways to distinguish between cancerous and benign
conditions, and between slow-growing cancers and fast-growing, potentially
lethal cancers. Some of the methods being studied are:
* PSA velocity: PSA velocity is the change in PSA levels over time. A sharp rise
in the PSA level raises the suspicion of cancer and may indicate a fast growing
cancer. A 2006 study found that men who had a PSA velocity above 0.35 ng/mL per
year had a higher relative risk of dying from prostate cancer than men who had a
PSA velocity less than 0.35 ng/mL per year (5). More studies are needed to
determine if high PSA velocity more accurately detects prostate cancer early.
* Age-adjusted PSA: Age is an important factor in increasing PSA levels. For
this reason, some doctors use age-adjusted PSA levels to determine when
diagnostic tests are needed. When age-adjusted PSA levels are used, a different
PSA level is defined as normal for each 10-year age group. Doctors who use this
method generally suggest that men younger than age 50 should have a PSA level
below 2.4 ng/mL, while a PSA level up to 6.5 ng/mL would be considered normal
for men in their 70s. Doctors do not agree about the accuracy and usefulness of
age-adjusted PSA levels.
* PSA density: PSA density considers the relationship of the PSA level to the
size of the prostate. In other words, an elevated PSA might not arouse suspicion
if a man has a very enlarged prostate. The use of PSA density to interpret PSA
results is controversial because cancer might be overlooked in a man with an
enlarged prostate.
* Free versus attached PSA: PSA circulates in the blood in two forms: free or
attached to a protein molecule. The free PSA test is more often used for men who
have higher PSA values. Free PSA may help tell what kind of prostate problem a
man has. With benign prostate conditions (such as BPH), there is more free PSA,
while cancer produces more of the attached form. If a man’s attached PSA is high
but his free PSA is not, the presence of cancer is more likely. In this case,
more testing, such as prostate biopsy, may be done. Researchers are exploring
different ways to measure PSA and to compare these measurements to determine if
cancer is present.
* Alteration of PSA cutoff level: Some researchers have suggested lowering the
cutoff levels that determine if a PSA measurement is normal or elevated. For
example, a number of studies have used cutoff levels of 2.5 or 3.0 ng/mL (rather
than 4.0 ng/mL). In such studies, PSA measurements above 2.5 or 3.0 ng/mL are
considered elevated. Researchers hope that using these lower cutoff levels will
increase the chance of detecting prostate cancer; however, this method may also
increase overdiagnosis and false positive test results and lead to unnecessary
medical procedures.
* Protein patterns: Scientists are also studying a test that can rapidly analyze
the patterns of various proteins in the blood. Researchers hope that this
technique can determine if a biopsy is necessary when a person has a slightly
elevated PSA level or an abnormal DRE.
For additional information about prostate cancer, contact the NCI’s Cancer
Information Service
