What is the PSA test?
antigen, or PSA, is a protein produced by cells of the prostate gland. The PSA
test measures the level of PSA in a man’s blood. For this test, a blood sample
is sent to a laboratory for analysis. The results are usually reported as
nanograms of PSA per milliliter(ng/mL) of blood.
The blood level of PSA
is often elevated in men with prostate cancer, and the PSA test was originally
approved by the FDA in 1986 to monitor the progression of prostate cancer in
men who had already been diagnosed with the disease. In 1994, the FDA approved
the use of the PSA test in conjunction with a digital rectal exam (DRE) to test asymptomatic men for prostate cancer. Men who report
prostate symptoms often undergo PSA testing (along with a DRE) to help doctors
determine the nature of the problem.
In addition to
prostate cancer, a number of benign (not cancerous) conditions can cause a
man’s PSA level to rise. The most frequent benign prostate conditions that
cause an elevation in PSA level are prostatitis (inflammation of the prostate)
and benign prostatic hyperplasia (BPH) (enlargement of the prostate). There is
no evidence that prostatitis or BPH leads to prostate cancer, but it is
possible for a man to have one or both of these conditions and to develop
prostate cancer as well.
Is the PSA test recommended for
prostate cancer screening?
Until recently, many
doctors and professional organizations encouraged yearly PSA screening for men
beginning at age 50. Some organizations recommended that men who are at higher
risk of prostate cancer, including African American men and men whose father or
brother had prostate cancer, begin screening at age 40 or 45. However, as more
has been learned about both the benefits and harms of prostate cancer screening
(see Questions 5 and 6), a number of organizations have begun to caution
against routine population screening. Although some organizations continue to
recommend PSA screening, there is widespread agreement that any man who is
considering getting tested should first be informed in detail about the
potential harms and benefits.
What is a normal PSA test
There is no specific
normal or abnormal level of PSA in the blood. In the past, most doctors
considered PSA levels of 4.0 ng/mL and lower as normal. Therefore, if a man had
a PSA level above 4.0 ng/mL, doctors would often recommend a prostate biopsy to determine whether prostate cancer was
However, more recent
studies have shown that some men with PSA levels below 4.0 ng/mL have prostate
cancer and that many men with higher levels do not have prostate cancer (1). In addition, various factors can cause a
man’s PSA level to fluctuate. For example, a man’s PSA level often rises if he
has prostatitis or a urinary tract infection. Prostate biopsies and prostate
surgery also increase PSA level. Conversely, some drugs—including finasteride and dutasteride, which
are used to treat BPH—lower a man’s PSA level. PSA level may also
vary somewhat across testing laboratories.
factor is that studies to establish the normal range of PSA levels have been
conducted primarily in populations of white men. Although expert opinions vary,
there is no clear consensus regarding the optimal PSA threshold for
recommending a prostate biopsy for men of any racial or ethnic group.
In general, however,
the higher a man’s PSA level, the more likely it is that he has prostate
cancer. Moreover, continuous rise in a man’s PSA level over time may also be a
sign of prostate cancer.
What if a screening test shows
an elevated PSA level?
If a man who has no
symptoms of prostate cancer chooses to undergo prostate cancer screening and is
found to have an elevated PSA level, the doctor may recommend another PSA test
to confirm the original finding. If the PSA level is still high, the doctor may
recommend that the man continue with PSA tests and DREs at regular intervals to
watch for any changes over time.
If a man’s PSA level
continues to rise or if a suspicious lump is detected during a DRE, the doctor
may recommend additional tests to determine the nature of the problem. A urine
test may be recommended to check for a urinary tract infection. The doctor may
also recommend imaging tests, such as a transrectal ultrasound, x-rays, or cystoscopy.
If prostate cancer is
suspected, the doctor will recommend a prostate biopsy. During this procedure,
multiple samples of prostate tissue are collected by inserting hollow needles
into the prostate and then withdrawing them. Most often, the needles are
inserted through the wall of the rectum (transrectal biopsy);
however, the needles may also be inserted through the skin between the scrotum
and the anus (transperineal biopsy).
A pathologist then examines the collected tissue under a microscope. The doctor may use ultrasound to view the
prostate during the biopsy, but ultrasound cannot be used alone to diagnose
What are some of the
limitations and potential harms of the PSA test for prostate cancer
cancer early may not reduce the chance of dying from prostate cancer. When used in screening, the PSA test can help
detect small tumors that do not cause symptoms. Finding a small tumor, however,
may not necessarily reduce a man’s chance of dying from prostate cancer. Some
tumors found through PSA testing grow so slowly that they are unlikely to
threaten a man’s life. Detecting tumors that are not life threatening is called
“overdiagnosis,” and treating these tumors is called “overtreatment.”
men unnecessarily to the potential complications and harmful side effects of treatments for early prostate cancer,
including surgery and radiation therapy. The side effects of these treatments
include urinary incontinence (inability to control urine flow), problems with bowel function, erectile dysfunction (loss of erections, or having erections that are inadequate for
sexual intercourse), and infection.
In addition, finding
cancer early may not help a man who has a fast-growing or aggressive tumor that
may have spread to other parts of the body before being detected.
The PSA test may give
false-positive or false-negative results. A false-positive test result occurs when a man’s PSA level is
elevated but no cancer is actually present. A false-positive test result may
create anxiety for a man and his family and lead to
additional medical procedures, such as a prostate biopsy, that can be harmful.
Possible side effects of biopsies include serious infections, pain, and
Most men with an
elevated PSA level turn out not to have prostate cancer; only about 25 percent
of men who have a prostate biopsy due to an elevated PSA level actually have
prostate cancer (2).
A false-negative test
result occurs when a man’s PSA level is low even though he actually has
prostate cancer. False-negative test results may give a man, his family, and
his doctor false assurance that he does not have cancer, when he may in fact
have a cancer that requires treatment.
What research has been done to
study prostate cancer screening?
Several randomized trials of prostate cancer screening have been
carried out. One of the largest is the Prostate, Lung, Colorectal, and Ovarian
(PLCO) Cancer Screening Trial, which NCI conducted to determine whether certain
screening tests can help reduce the numbers of deaths from several common
cancers. In the prostate portion of the trial, the PSA test and DRE were
evaluated for their ability to decrease a man’s chances of dying from prostate
The PLCO investigators
found that men who underwent annual prostate cancer screening had a higher incidence of prostate cancer than men in the control group but the same rate of deaths from the disease (3). Overall, the results suggest that many men
were treated for prostate cancers that would not have been detected in their
lifetime without screening. Consequently, these men were exposed unnecessarily
to the potential harms of treatment.
A second large trial,
the European Randomized Study of Screening for Prostate Cancer (ERSPC),
compared prostate cancer deaths in men randomly assigned to PSA-based screening
or no screening. As in the PLCO, men in ERSPC who were screened for prostate
cancer had a higher incidence of the disease than control men. In contrast to
the PLCO, however, men who were screened had a lower rate of death from
prostate cancer (4).
The United States
Preventive Services Task Force has analyzed the data from the PLCO, ERSPC, and
other trials and estimated that, for every 1,000 men ages 55 to 69 years who
are screened every 1 to 4 years for a decade (5):
o 0 to 1 death from
prostate cancer would be avoided.
o 100 to 120 men would
have a false-positive test
result that leads to a
biopsy, and about one-third of the men who get a biopsy would experience at
least moderately bothersome symptoms from the biopsy.
o 110 men would be
diagnosed with prostate cancer. About 50 of these men would have a complication
from treatment, including erectile dysfunction in 29 men, urinary incontinencein 18 men, serious cardiovascular events in 2
men, deep vein thrombosis or pulmonaryembolism in 1 man, and death due to the treatment in
less than 1 man.
How is the PSA test used in men
who have been treated for prostate cancer?
The PSA test is used
to monitor patients who have a history of prostate cancer to see if their
cancer has recurred (come back). If a man’s PSA level begins to rise after
prostate cancer treatment, it may be the first sign of a recurrence. Such a “biochemical relapse” typically appears months or years before
other clinical signs and symptoms of prostate cancer recurrence.
However, a single
elevated PSA measurement in a patient who has a history of prostate cancer does
not always mean that 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 a recurrence. The doctor may look for a trend of rising PSA
level over time rather than a single elevated PSA level.
What does an increase in PSA
level mean for a man who has been treated for prostate cancer?
If a man’s PSA level
rises after prostate cancer treatment, his doctor will consider a number of
factors before recommending further treatment. Additional treatment based on a
single PSA test is not recommended. Instead, a rising trend in PSA level over
time in combination with other findings, such as an abnormal result on imaging
tests, may lead a man’s doctor to recommend further treatment.
How are researchers trying to
improve the PSA test?
investigating ways to improve the PSA test to give doctors the ability to
better distinguish cancerous from benign conditions and slow-growing cancers from
fast-growing, potentially lethal cancers. Some of the methods being studied
o Free versus total PSA. The amount of PSA in the blood that is
“free” (not bound to other proteins) divided by the total amount of PSA (free
plus bound). Some evidence suggests that a lower proportion of free PSA may be
associated with more aggressive cancer.
o PSA density of the
transition zone. The blood level of
PSA divided by the volume of the transition zone of the prostate. The
transition zone is the interior part of the prostate that surrounds the urethra. Some evidence suggests that this measure may
be more accurate at detecting prostate cancer than the standard PSA test.
o Age-specific PSA
reference ranges. Because a man’s PSA
level tends to increase with age, it has been suggested that the use of
age-specific PSA reference ranges may increase the accuracy of PSA tests.
However, age-specific reference ranges have not been generally favored because
their use may delay the detection of prostate cancer in many men.
o PSA velocity and PSA
doubling time. PSA velocity is the
rate of change in a man’s PSA level over time, expressed as ng/mL per year. PSA
doubling time is the period of time over which a man’s PSA level doubles. Some
evidence suggests that the rate of increase in a man’s PSA level may be helpful
in predicting whether he has prostate cancer.
o Pro-PSA. Pro-PSA refers to several different inactive
precursors of PSA. There is some evidence that pro-PSA is more strongly
associated with prostate cancer than with BPH. One recently approved test combines
measurement of a form of pro-PSA called [-2]proPSA with measurements of PSA and
free PSA. The resulting “prostate health index” can be used to help a man with
a PSA level of between 4 and 10 ng/mL decide whether he should have a biopsy.