The PSA Test: What Do The Numbers Mean?

As described previously, the PSA test checks the blood for minute quantities of an enzyme called prostate-specific antigen or PSA. A higher than normal amount of PSA in the blood is a possible indicator of prostate cancer, although other conditions of the prostate, such as benign prostatic hyperplasia and prostatitis, also elevate PSA levels. CPCN recommends that men between 40 and 45 get a preliminary PSA test to serve as a benchmark and that they get the actual PSA test numbers from their physicians, not settling for a general response such as "You're fine." (Please click here for more information on the use of the PSA test in the early detection of prostate cancer.)

So you have the PSA test, and you get the actual results, but what do the numbers mean? What is a higher than normal amount of prostate-specific antigen? Here are the general guidelines:


Remember, high PSA readings do not mean that you have prostate cancer. Many factors can contribute to an abnormally high level of PSA in the blood, and the general guidelines presented above are usually adjusted for some of these factors.

AGE
Aging increases the amount of PSA in the blood, so normal PSA levels are adjusted for age. Any PSA level of under 4 nanograms per millilitre (ng/ml) used to be considered insignificant. With more knowledge about the effects of aging on PSA levels, however, doctors would probably consider a reading of above 2.5 significant for a 45-year-old man and call for further testing.

The normal range of PSA levels for men in each age group


RACE
A man's race also affects not only his risk of developing prostate cancer but also the amount of prostate-specific antigen that is within the normal range. Today, doctors may consider both a man's age and his race when determining whether his PSA test result is unusual. The following table shows age- and race-adjusted cut-off values for PSA, in other words, the PSA levels at the top end of the normal range for men of particular ages and races.

Age- and race-adjusted cut-off values for PSA


OTHER CONDITIONS OF THE PROSTATE
Benign prostatic hyperplasia (BPH) and prostatitis can also increase the amount of PSA found in a man's blood. BPH, a non-cancerous enlargement of the prostate, can elevate PSA levels because a larger prostate manufactures more prostate-specific antigen. Also, any prostate condition can weaken the tissues in the prostate gland, allowing more PSA to leak into the blood. Usually, PSA levels caused by BPH do not go as high as those caused by prostate cancer, nor do the levels tend to rise as quickly in the case of BPH. However, most likely, if you have a higher than normal PSA level or one that is steadily rising, your doctor will discuss the value of having a prostate biopsy to determine whether cancer or some other condition is to blame. Prostatitis, an inflammation of the prostate, can also affect PSA levels. Because this inflammation can break down tissues in the prostate gland, it can enable quite a bit of prostate-specific antigen to escape fairly quickly into the blood. An acutely inflamed or infected prostate can increase a man's PSA level to 100 nanograms per millilitre (ng/ml) or higher. After treatment for prostatitis, it can take up to six months for PSA levels to return to normal.

RELIABILITY OF THE PSA TEST
So many factors can affect the level of prostate-specific antigen in the blood that one might ask whether the PSA test is useful in the diagnosis of prostate cancer. The answer is a resounding yes. The PSA test, especially when combined with a digital rectal examination, is the best indicator of the possibility of prostate cancer. The PSA test does not predict either the presence or absence of prostate cancer, but it does alert men and their physicians to the possibility of the presence of an early-stage cancer in the prostate, a possibility that they can investigate further with a biopsy.

Still, there is considerable controversy over the value of the PSA test. Some studies report that no prostate cancer was found in 70 to 80 per cent of the men who had a biopsy because of an elevated PSA level. That's 3 to 4 of every 5 men. The medical community calls a higher than normal PSA level with no evidence of prostate cancer a false positive. Also, some researchers estimate that 20 per cent of prostate cancers would be missed if doctors relied only on PSA test results. In other words, 1 man of 5 tested would have prostate cancer and a normal PSA level. A PSA level in the normal range with the presence of prostate cancer is called a false negative.

Health Canada presents these statistics in another way. After a PSA test of 100 men, approximately 90 will have normal and 10 will have elevated PSA levels. Of these 10, 3 will go on to discover that they have prostate cancer after their first biopsy, and 7 will get biopsy results that find no cancer. However, of these 7, 2 will discover they have cancer during follow-up tests. So, approximately 5 of the 10 men may have been helped to an early diagnosis of prostate cancer through the test. Of the 90 men who had normal PSA levels, 1 or 2 will actually have prostate cancer.


People seeing these statistics might conclude that the PSA test is not useful because it is unreliable. This is a mistake. An abnormally high PSA level indicates the possibility of prostate cancer, just as a suspicious looking area of a mammogram indicates the possibility of breast cancer in a woman. In fact, some research suggests that the PSA test, when combined with a digital rectal examination, is as accurate a screening mechanism for prostate cancer as a mammogram and a physical exam is for breast cancer.

Still, doctors will probably advise at least one other blood test in a few weeks if your first one showed an abnormally high level of PSA. One reason for this is that a man's PSA level can fluctuate over the course of a few days, and doctors often want to include consideration of this fluctuation before discussing whether a biopsy would be prudent.

Related information: "What is a false positive?" CPCN Lawrence Koltz, "The Truth about PSA Testing," CPCN "The Prostate-Specific Antigen (PSA) Test: Questions and Answers," US National Cancer Institute,

REFINEMENTS
To improve the usefulness of the PSA test as an indicator of prostate cancer and to sort out whether a patient is more likely to have prostate cancer as opposed to another condition, physicians have made some refinements to the PSA test and to the analysis of PSA test results. Doctors now consider the speed at which PSA levels rise (PSA velocity), how quickly PSA levels double in amount (PSA doubling time), the sort of prostate-specific antigen in the blood (free versus total PSA), and the amount of PSA in relation to the size of a man's prostate (PSA density).

PSA velocity: PSA velocity is a measure of how quickly the levels of prostate-specific antigen increase over a period of time. The rate at which these levels increase is faster in men with cancer than in those with BPH or a normal prostate, so the faster a man's PSA levels rise over time, the greater the risk that cancer is to blame. Usually, measuring PSA velocity requires at least three PSA tests over about one and a half years. Still, it is difficult to get an accurate measurement of PSA velocity because of the normal daily fluctuation of PSA levels.

PSA doubling time: Like PSA velocity, PSA doubling time relates PSA levels to time. It measures the time it takes for your PSA value to double. Sometimes, PSA doubling time is helpful in pre-biopsy guesses about whether a man has cancer and whether this cancer is likely to be aggressive or to have spread.

Percentage of Free to Total PSA (%fPSA): This measurement is a ratio comparing the amount of free PSA to the total amount of PSA in the blood. Free PSA travels alone in the blood; it is not bound to any other blood proteins.


This unbound or free PSA comes from BPH, not prostate cancer. So the higher a man's percentage of free PSA, the less likely it is that prostate cancer is to blame. Testing for free PSA (called %fPSA in some medical reports) is useful for men whose PSA level falls between 4 and 10-the grey area in which BPH could be the culprit. Readings of greater than 25 per cent free PSA (25 %fPSA) indicate that much of the elevated PSA is caused by BPH. A reading of under 10% suggests that prostate cancer is causing this elevation and, furthermore, that this cancer is probably large and in need of immediate treatment. The following graph from Dr. Ronald A. Morton's online course offered by the Baylor College of Medicine shows how determining the percentage of free to total PSA may help in the diagnosis of prostate cancer.



PSA density (PSAD): This measurement compares the size of a man's prostate, which is determined by a transrectal ultrasound (TRUS), with his PSA level. In simple terms, the doctor divides the PSA value by the size (or volume) of the prostate. If, for example, your PSA level is 4 and the size of your prostate in grams is 32, you would divide 4 by 32 to get a PSA density of 0.125. Usually, a PSA density under 0.07 is considered fairly safe, one between 0.07 and 0.15 could be attributable to either benign prostatic hyperplasia (BPH) or prostate cancer, and one above 0.15 indicates an increased likelihood that cancer is present.

Related information: Dr. Tom Pickles, "What's our next move: Understand the latest research on PSA screening," Our Voice, 2, no. 1, pp. 5-7. CPCN Dr . Aron Mathur, "January notes on prostate cancer treatments," CPCN Peter E. Levers, "Prostate cancer: A clinical overview" describes the use of the PSA in prostate cancer diagnosis, CPCN R. S. Punglia, A. V. D'Amico, W. J. Catalon, K. A. Roehl, and K. M. Kuntz, "Effects of verification bias on screening for prostate cancer by measurement of prostate-specific antigen," New England Journal of Medicine, 349(4), July 24, 2003, CPCN Jonathan McDermed, "Using PSA Intelligently to Manage Prostate Cancer," Prostate Cancer Research Institute