The total PSA test and digital rectal exam (DRE) are ordered to screen both asymptomatic and symptomatic men for prostate cancer. Since the DRE can cause a temporary elevation in PSA, the blood is usually collected prior to performing the DRE. If either the PSA or the DRE are found to be abnormal, then the doctor may choose to follow this testing with a prostate biopsy and perhaps imaging tests, such as an ultrasound. If the DRE is normal but the PSA is moderately elevated, the doctor may order a free PSA test 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. Since the total PSA test can be elevated temporarily for a variety of reasons, a doctor may order another PSA a few weeks after the first to determine if the PSA is still elevated.

The cPSA is a relatively new test that may be ordered, along with the DRE, as an alternative to the total PSA. There is hope that this test could be more specific than the total PSA (better at detecting cancer-related PSA), but findings have been mixed and its ultimate clinical utility has yet to be established. The cPSA is an option that doctors can discuss with their patients. Its use may expand and/or be better defined as additional studies are conducted and findings are reported.

If prostate cancer is diagnosed, then the total PSA 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.

In cases where the cancer appears to be slow-growing and the doctor and patient decide to monitor its progress rather than pursue immediate treatment (called “watchful waiting”), total PSA levels are ordered at frequent intervals to monitor the change in PSA over time.

There is no consensus among the experts currently about when the PSA test should be ordered to screen asymptomatic males. Over-diagnosing, identifying cases of prostate cancer that may never cause significant health problems, must be balanced against missing the detection of aggressive cancers. There are national organizations, such as the National Cancer Institute and Centers for Disease Control and Prevention, that do not recommend routine screening at this time. Others, such as the American Cancer Society (ACS), recommend that doctors offer total PSA tests and DRE annually to all men, beginning at age 50 and to those at an increased risk of prostate cancer, such as American men of African descent and men with a family history of the disease, beginning at age 40 or 45. The ACS recommends that doctors discuss the testing options, benefits, and potential side effects with their male patients so that they can make informed choices. (See Prostate Cancer Screening for Adults and Adults 50 and Up.) The total PSA test and DRE may also be ordered when a patient has symptoms that could be due to prostate cancer, such as difficult, painful, and/or frequent urination, back pain, and/or pelvic pain. Since these symptoms are seen with a variety of other conditions, including infection and prostatitis, the doctor will also frequently order other tests, such as a urine culture. Some of these conditions can themselves cause temporary increases in PSA levels. If a total PSA level is elevated, a doctor 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 patient has a moderately elevated total PSA that does not appear to be caused by a non-cancer-related condition. The results give the doctor additional information about whether a patient 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 during treatment of patients who have been diagnosed with prostate cancer to verify the effectiveness of treatment and at regular intervals after treatment to monitor for cancer recurrence. It is also ordered at regular intervals when a patient with cancer is participating in “watchful waiting” and not currently treating their prostate cancer.

The normal value for total PSA has been set at less than 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 exacerbate over-diagnosing and over-treating cancers that are not clinically significant.

There is agreement that patients with a total PSA level greater than 10.0 ng/ml are at an increased risk for prostate cancer (more than a 67% chance, according to the ACS). Levels between 4.0 ng/ml and 10.0 ng/ml may indicate prostate cancer (about a 25% chance, according to the ACS), BPH, or prostatitis. These conditions are more common in the elderly, as is a general increase in PSA levels. Concentrations of total PSA between 4.0 ng/ml and 10.0 ng/ml are often referred to as the “gray zone.” It is in this range that the free PSA is the most useful. When patients in the gray zone have decreased levels of free PSA, they have a higher probability of prostate cancer; when they have elevated levels of free PSA, the risk is diminished. The ratio of free to total PSA can help the doctor decide whether or not a prostate biopsy should be performed.

When the cPSA test is used as a screening tool, increased levels may indicate an increased risk of prostate cancer, while lower levels indicate a decreased risk.

In addition to the introduction of the free PSA and cPSA tests, there have been efforts to increase the usefulness of the total PSA as a screening tool. While none of these efforts have been widely accepted yet, researchers are studying them and some doctors are utilizing them. They include:

PSA velocity. This is the change in PSA concentrations over time. If the PSA continues to rise significantly over time (such as 3 or more years), then it is more likely that prostate cancer is present. If it climbs rapidly, then the patient may have a more aggressive form of cancer.

PSA doubling time. This is another version of the PSA velocity. It measures how rapidly the PSA concentration doubles.

PSA density. This is a comparison of the PSA concentration and the volume of the prostate (as measured by ultrasound). Patients with larger prostates tend to produce more PSA, so this factor is an adjustment to compensate for the size.

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 patient for recurrence. Since even tiny increases can be significant, patients may want to have their monitoring PSA tests done by the same laboratory each time so that testing variation is kept to a minimum.

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 levels. Excessive 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 recent 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 physicians will prescribe a course of antibiotics if there is evidence that there is infection of the prostate.