Prostate Specific Antigen (PSA)
When you have symptoms suggestive of prostate cancer such as difficult, painful, and/or frequent urination; may also be ordered during and at regular intervals after prostate cancer treatment; in asymptomatic men, after a discussion with your healthcare practitioner about the benefits and harms of screening (For specific details, see prostate cancer screening for Adults and Adults 50 and Up).
A blood sample drawn from a vein
Avoid ejaculation for 24 hours before sample collection as it has been associated with elevated PSA levels; avoid rigorous physical activity like bike riding; certain medications and herbal supplements can also affect PSA levels so be sure to tell your healthcare practitioner about any of these you are currently taking; the sample should be collected prior to your healthcare practitioner performing a digital rectal exam (DRE) and prior to (or several weeks after) a prostate biopsy as both of these can elevate PSA levels.
Prostate specific antigen (PSA) is a protein produced primarily by cells in the prostate, a small gland in males that encircles the urethra and produces a fluid that makes up part of semen. Most of the PSA that the prostate produces is released into this fluid, but small amounts of it are also released into the blood. PSA exists in two main forms in the blood: complexed (cPSA, bound to other proteins) and free (fPSA, not bound). The most frequently used PSA test is the total PSA, which measures the sum of cPSA and fPSA in the blood.
The PSA test may be used as a tumor marker to screen for and to monitor prostate cancer. The goal of screening is to detect prostate cancer while it is still confined to the prostate. However, most experts agree that screening should be done on asymptomatic men only after thorough discussions with their healthcare practitioners on the benefits and risks and after informed decisions are made to undergo screening. Elevated blood levels of PSA are associated with prostate cancer, but they may also be seen with inflammation of the prostate (prostatitis) and benign prostatic hyperplasia (BPH). PSA levels tend to increase in all men as they age, and men of African American heritage may have levels that are higher than other men, even at earlier ages.
PSA is not diagnostic of cancer. The gold standard for identifying prostate cancer is the prostate biopsy, collecting small samples of prostate tissue and identifying abnormal cells under the microscope. An elevated PSA may be followed by a biopsy, which has risk of complications such as pain, fever, blood in the urine, or urinary tract infection. (Read the article on Anatomic Pathology for more information on biopsies.) The total PSA test and digital rectal exam (DRE) are used together to help determine the need for a prostate biopsy.
Once the presence of prostate cancer is confirmed by biopsy, another decision must be made with regard to treatment. Prostate cancer is relatively common in men as they age and many, if not most, of the tumors are very slow-growing. While prostate cancer is the number two cause of cancer death in men, the slow-growing type is an uncommon cause of death and may never cause symptoms. A pathologist may be able to help differentiate between slow-growing cases and cancers that are likely to grow aggressively and spread to other parts of the body (metastasize).
Over-diagnosis and over-treatment of prostate cancer are issues with which health practitioners are currently grappling. In some cases, the treatment can be worse than the cancer, with the potential for causing significant side effects such as incontinence and erectile dysfunction. The PSA test and DRE cannot, in general, predict the course of a person's disease. The free PSA test is sometimes used to help determine if a biopsy should be done when the total PSA is only slightly elevated.
How is the test used?
The PSA test and digital rectal exam (DRE) may be used to screen both asymptomatic and symptomatic men for prostate cancer. PSA exists in two forms in the blood: free (fPSA, not bound) and complexed (cPSA, bound to other proteins). Lab tests can measure fPSA or total PSA (cPSA plus fPSA).
Most organizations, including the U.S. Preventive Services Task Force, the American Cancer Society, and the American Urological Association, recommend that men discuss the advantages and disadvantages of PSA-based screening for prostate cancer with their healthcare practitioner before making an informed decision about whether to be screened or not.
The total PSA test can be elevated temporarily for a variety of reasons. If an initial PSA is elevated, another PSA test may be done a few weeks after the first to determine if the PSA is still elevated. If the repeat test is elevated, a healthcare practitioner may recommend that a series of PSA tests be done over time to determine whether the level goes down, stays elevated at about the same level, or continues to increase. In cases where the cancer appears to be slow-growing, the healthcare practitioner and patient may decide to monitor its progress rather than pursue immediate treatment (called "watchful waiting" or "active surveillance").
If the DRE is normal but the PSA is moderately elevated, a free PSA test may be used to look at the ratio of free to total PSA. This can help to distinguish between prostate cancer and other non-cancer causes of elevated PSA.
If prostate cancer is diagnosed, the total PSA test may be used as a monitoring tool to help determine the effectiveness of treatment. It may also be ordered at regular intervals after treatment to detect recurrence of the cancer.
When is it ordered?
For men who wish to be screened for prostate cancer, the American Cancer Society recommends that healthy men of average risk and at least a 10-year expectancy consider waiting to get tested until age 50, while the American Urological Association recommends screening for men between the ages of 55 and 69 with no routine screening after age 70 or for any man with less than a 10- to 15-year life expectancy.
For those at high risk, such as African American men and men with a family history of the disease, the recommendation is to consider beginning testing at age 40 or 45. (See Screening Tests for Adults (30-49): Prostate cancer and Screening Tests for Adults (50 and Up): Prostate cancer for details on screening recommendations.)
The total PSA test and digital rectal exam (DRE) may also be ordered when you have symptoms that could be due to prostate cancer, such as difficult, painful, and/or frequent urination, back pain, and/or pelvic pain.
If a total PSA level is elevated, a healthcare practitioner may order a repeat test a few weeks later to determine whether the PSA concentrations have returned to normal.
A free PSA test is primarily ordered when you have a moderately elevated total PSA. The results give your healthcare practitioner additional information about whether you have increased risk of having prostate cancer and help with the decision of whether to biopsy the prostate.
The total PSA may be ordered at regular intervals during treatment of prostate cancer or during "watchful waiting" or "active surveillance" of prostate cancer.
What does the test result mean?
PSA test results can be interpreted a number of different ways and there may be differences in cutoff values between different laboratories.
- Many experts consider a PSA level less than 4.0 ng/ml (nanograms per milliliter of blood) to mean that it is unlikely that you have prostate cancer. However, some feel that this level should be lowered to 2.5 ng/ml in order to detect more cases of prostate cancer. Yet, others argue that this would lead to more over-diagnosing and over-treating cancers that are not clinically significant.
- There is agreement that a total PSA level greater than 10.0 ng/ml indicates an increased risk for prostate cancer (more than a 50% chance, according to the American Cancer Society, (ACS)).
- Total PSA levels between 4.0 ng/ml and 10.0 ng/ml may indicate prostate cancer (about a 25% chance, according to the ACS), benign prostate hyperplasia (BPH), or inflammation of the prostate. These conditions are more common in the elderly, as is a general increase in PSA levels. Total PSA between 4.0 ng/ml and 10.0 ng/ml is often referred to as the "gray zone." It is in this range that the free PSA may be useful (see next bullet).
- Free PSA—prostate tumors typically produce mostly complexed PSA (cPSA), not free PSA (fPSA). Benign prostate cells tend to produce more free PSA, which will not complex with proteins. Thus, when men in the gray zone have decreased levels of free PSA, it means that they have increased cPSA and a higher probability of prostate cancer. Conversely, when they have elevated levels of free PSA and low cPSA, the risk is diminished. The ratio of free to total PSA can help the individual and his healthcare practitioner decide whether or not a prostate biopsy should be performed.
Additional evaluations of the PSA test results are sometimes used in an effort to increase the usefulness of the total PSA as a screening tool. They include:
- Age-specific PSA ranges—since PSA levels naturally increase as a man ages, it has been proposed that normal ranges be tailored to a man's age.
- PSA velocity—the change in PSA concentrations over time; if the PSA continues to rise significantly over time (at least 3 samples at least 18 months apart), then it is more likely that prostate cancer is present. If it climbs rapidly, then the affected person may have a more aggressive form of cancer.
- PSA doubling time—another version of the PSA velocity test; it measures how rapidly the PSA concentration doubles.
- PSA density—a comparison of the PSA concentration and the volume of the prostate (as measured by ultrasound); if the PSA level is greater than what one would expect given the size of the prostate, the chance that a cancer is present may be higher.
During treatment for prostate cancer, the PSA level should begin to fall. At the end of treatment, it should be at very low or undetectable levels in the blood. If concentrations do not fall to very low levels, then the treatment has not been fully effective. Following treatment, the PSA test is performed at regular intervals to monitor the person for cancer recurrence. Since even tiny increases can be significant, those affected may want to have their monitoring PSA tests done by the same laboratory each time so that testing variation is kept to a minimum.
Will PSA testing detect all prostate cancers?
What is the Prostate Health Index (PHI)?
What is PSA isoform p2PSA?
p2PSA is a test that measures the levels of PSA isoform p2PSA in the blood to predict prostate cancer in men with elevated total PSA levels prior to biopsy. This test may also help identify aggressive forms of prostate cancer. The accuracy of prostate cancer diagnosis is improved when p2PSA test results are combined with total and fPSA test results.
What are some other tests that may be done when the PSA level is only slightly elevated to help decide whether a prostate cancer is present?
Although PSA can help detect cancer, there are sometimes false-positive results, especially when the PSA is only slightly elevated. Biopsies used in follow-up to positive PSA results can cause discomfort, anxiety, and sometimes complications. As these tests becomes more widely available, they may aid some men and their healthcare practitioners in decisions about their future care:
- PCA3—PCA3 is a protein produced only in the prostate gland. The test measures the urine level of PCA3 messenger RNA (m-RNA), a signal from genes that tells the prostate to produce the PCA3 protein. Increased amounts of the m-RNA (over-expressed) are produced by 95% of prostate cancer cells, so an elevated level may help to indicate that a prostate cancer is present.
- [-2] proPSA—this test looks for a precursor of PSA, which may be produced by prostate cancer cells at a higher rate than benign prostate cells. The percentage of [-2] proPSA relative to the total PSA level has been used, like the % free PSA, to help decide whether a biopsy is indicated.
- TMPRSS2-ERG gene fusion—this test is also a urine-based assay that detects mRNA that is the result of a gene rearrangement. The gene rearrangement is over-expressed in more than 50% of prostate cancers, so an elevated level may help to indicate that a prostate cancer is present.
These tests do not provide a definitive answer as to whether you have a prostate cancer or not. A positive biopsy remains the gold standard in diagnosing prostate cancer. Rather, they are intended to help predict whether a biopsy would be useful in helping to establish a diagnosis.
What are some tests that may be done to help decide whether a prostate cancer is likely to be fast-growing and spread (metastasize) and therefore should be removed rather than watched?
- Gleason scoring—this refers to a part of the pathologist's report after reviewing the biopsy of the prostate that describes the degree to which certain features of prostate cancer known to be associated with a poor prognosis are present in the patient's cancer.
- Prostate gene expression profile—this is a test in which the prostate cancer in the biopsy is analyzed using genetic techniques to determine the degree of activation of certain genes known to be associated with poor prognosis.
- TMPRSS2-ERG gene fusion—this urine test, sometimes used to help determine if a biopsy is needed, has also been shown to help predict how the cancer will behave.
Although Gleason scoring is performed on all new prostate cancers discovered by biopsy, the other tests are still undergoing study. It is fair to say that there is no easy way to determine whether a prostate cancer will spread and grow quickly or will be a slow-growing cancer unlikely to cause the person's death. This makes the decision to undergo PSA testing and, if PSA is elevated, prostate biopsy, an important one.
I’ve heard of "ultrasensitive PSA." What is it?
A test called "ultrasensitive PSA" (USPSA) may be useful in monitoring for persistence or recurrence of cancer after treatment. This test detects PSA at much lower levels than the traditional test. It has been suggested that increases in PSA due to the persistence or return of cancer can be identified much sooner with this test. However, results of this test must be interpreted with caution. Because the test is very sensitive, there can be small increases in PSA levels from one time to the next even when no cancer is present (false positive).
Is there anything else I should know?
In some men, PSA may rise temporarily due to other prostate conditions, especially infection. A study found that in about half of men with high levels of PSA, their PSA levels later return to normal. Some authorities recommend that a PSA test should be repeated between 6 weeks and 3 months after the first high PSA before taking any further action. Some healthcare practitioners will prescribe a course of antibiotics if there is evidence that there is infection of the prostate.