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Prostate specific antigen (PSA) is a protein produced primarily by cells in the prostate, a small gland that encircles the urethra in males 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 bloodstream. This test measures the amount of Total and Free PSA in the blood. The ratio of Free to Total PSA may help discriminate between prostate cancer and benign prostatic hyperplasia.

About

The PSA test is used as a tumour marker to screen for and to monitor prostate cancer. It is a good tool but not a perfect one, and most experts agree that screening should be done on asymptomatic men only after thorough discussions with their healthcare providers on the benefits and risks and after informed decisions are made to undergo screening. Elevated levels of PSA are associated with prostate cancer, but they may also be seen with 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. The total PSA test and digital rectal exam (DRE) are used together to help determine the need for a prostate biopsy.


The goal of screening is to detect prostate cancer while it is still confined to the prostate. 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 tumours, are very slow-growing. While prostate cancer is the number two cause of death in men, the slow-growing type is an uncommon cause of death. 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-diagnosing and over-treatment are issues with which health practitioners are currently grappling. In some cases, the treatment can be worse than 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.


PSA exists in two main forms in the blood: complexed (cPSA, bound to other proteins) and free (not bound). The most frequently used PSA test is the total PSA, which measures the sum of complexed and the free PSA in the blood.


The free PSA test is sometimes used to help to determine whether a biopsy should be done when the total PSA is only slightly elevated. PSA is an enzyme (a protein that helps different chemical reactions to occur) and when it is released into the blood, some circulating proteins inactivate PSA by binding to it. Benign prostate cells in BPH tend to release PSA that is not active (and, therefore, less likely to be bound by circulating proteins) and cancerous prostate cells tend to release PSA that is already protein-bound.


Therefore, men with BPH tend to have higher levels of free PSA and men with prostate cancer tend to have lower amounts of free PSA. A relatively low level of free PSA increases the chances that a cancer is present, even if the total PSA is not significantly elevated.


Preparation

Avoid ejaculation for 24 hours before sample collection as it has been associated with elevated PSA levels.

Indications

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.


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.


Interpretation

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 millilitre 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 "grey zone." It is in this range that the free PSA may be useful (see next bullet).
  • Free PSA—prostate tumours 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 grey 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.

Disclaimer

The laboratory test results are NOT to be interpreted as results of a "stand-alone" test. The test results have to be interpreted after correlating with suitable clinical findings and additional supplemental tests/information. Your healthcare providers will explain the meaning of your tests results, based on the overall clinical scenario. Certain medications that you may be currently taking may influence the outcome of the test. Hence, it is important to inform your healthcare provider of the complete list of medications (including any herbal supplements) you are currently taking. This will help the healthcare provider interpret your test results more accurately and avoid unnecessary chances of a misdiagnosis.

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