The PSA test and digital rectal exam (DRE) may be used to screen both asymptomatic and symptomatic men for prostate cancer. PSA is a protein produced primarily by cells in the prostate and most of the PSA is released into semen, but small amounts of it are also released into the blood. PSA exists in two forms in the blood: free (not bound) and complexed (cPSA, bound to other proteins). Lab tests can measure free PSA or total PSA (bound plus unbound).

Some organizations, such as the U.S. Preventive Services Task Force, feel that the harms associated with over-diagnosis and over-treatment outweigh the potential benefits and advise against using PSA to screen for prostate cancer in healthy men of any age. 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 provider before making an informed decision about whether to be screened or not.

While elevated PSA levels are associated with cancer, they may be caused by other conditions, such as benign prostatic hyperplasia (BPH) and inflammation of the prostate. 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 about biopsies.)

And though prostate cancer is a relatively common type of cancer in men and the number two cause of death, many prostate cancers are slow-growing. These slow-growing types may never cause symptoms or become life-threatening. Yet prostate cancer found through screening may be treated with surgery or radiation therapy, which can have serious side effects, such as incontinence or erectile dysfunction.

The total PSA test can be elevated temporarily for a variety of reasons, so if an initial PSA is elevated, another PSA 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 provider may recommend that series of PSAs be done over time to determine whether the level goes down, stays elevated, or continues to increase. In cases where the cancer appears to be slow-growing, the healthcare provider and patient may decide to monitor its progress rather than pursue immediate treatment (called "watchful waiting").

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.

Other tests may also be recommended if either the PSA or the DRE is found to be abnormal. A urinalysis may be done, for example, to check for urinary tract infection and imaging tests, such as an ultrasound, may be done to examine the prostate.

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.

For men who wish to be screened for prostate cancer, the American Cancer Society recommends that healthy men of average risk 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.

For those at high risk, such as American men of African descent 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 a man has 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 provider may order a repeat test a few weeks later to determine whether the PSA concentrations have returned to normal.

A free PSA is primarily ordered when a man has a moderately elevated total PSA. The results give the healthcare provider additional information about whether the person is at an 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 men who have been diagnosed with prostate cancer and when a man with cancer is participating in "watchful waiting" and not currently treating his prostate cancer.

PSA test results can be interpreted a number of different ways and there may be differences in cutoff values between different laboratories.

• The value for total PSA below which the presence of prostate cancer is considered to be unlikely is 4.0 ng/ml (nanograms per milliliter of blood). There are some that feel that this level should be lowered to 2.5 ng/ml in order to detect more cases of prostate cancer. Others argue that this would lead to more over-diagnosing and over-treating cancers that are not clinically significant.
• There is agreement that men with a total PSA level greater than 10.0 ng/ml are at 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. 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 provider 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:

• 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; 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.
• 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.

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.

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).

Since the DRE can cause a temporary elevation in PSA, the blood sample is usually collected prior to performing the DRE.

Prostate manipulation by biopsy or resection of the prostate will significantly elevate PSA levels. The blood test should be done before surgery or six weeks after manipulation.

Rigorous physical activity affecting the prostate, such as bicycle riding, may cause a temporary rise in PSA level. Ejaculation within 24 hours of testing can be associated with elevated PSA levels and should be avoided.

Large doses of some chemotherapeutic drugs, such as cyclophosphamide and methotrexate, may increase or decrease PSA levels.

In some men, PSA may rise temporarily due to other prostate conditions, especially infection. A study found that in about half of men with a high PSA, values later return to normal. Some authorities recommend that a high PSA should be repeated, between 6 weeks and 3 months after the high PSA, before taking any further action. Some health practitioners will prescribe a course of antibiotics if there is evidence that there is infection of the prostate.