Prostate Specific Antigen (PSA) and Prostate Cancer Screening

What is PSA and how is it measured?

PSA stands for "prostate specific antigen" and it is a blood test used to screen for the presence of prostate cancer.

The prostate is the gland found only in men that is located between the bladder and the urethra (the urinary channel that runs through the penis). The prostate's function is to make seminal fluid or semen that is ejaculated during intercourse. Note that sperm is made in the testicles and is only a small fraction of the seminal fluid. Antigen is a medical term for a substance, usually a protein, that stimulates the body to make antibodies.

Prostate specific antigen is, therefore, a protein found in the serum (serum is the fluid portion of blood) that is unique or specific to the prostate. No other human tissue or body part can make prostate specific antigen except for the prostate. The PSA levels can be measured in an individual's serum and with this information we are able to screen for prostate cancer.

Why use PSA to screen for prostate cancer?

The routine use of PSA testing along with rectal examination of the prostate has dramatically improved the ability to find prostate cancer earlier -- and possibly at a more curable stage -- than ever before. Controversy exists as to whether earlier diagnosis leads to longer survival, but it is our hope that PSA testing will lead to lives being saved because of earlier treatment.

What causes the PSA to rise?

PSA is only present in men in all normal prostate tissue. The normal prostate cell holds on to most of the PSA and lets very little leak into the blood stream. The small amount that leaks out is the PSA that is measured by the blood test. Prostate cancer cells actually have less PSA in each cell, but the cancer cell tends to leak more PSA into the bloodstream; hence the reason for measuring the PSA levels. Knowing this fact, we have come up with a range of expected values in patients with a normal prostate gland. We believe that the PSA value should be less than 4.0. This number is somewhat arbitrary but reflects the assumption that most men (about 95 percent) with normal prostate glands have a PSA value of 4.0 or less (see below about age-specific normal values). The catch is the word "normal." Almost any condition that affects the prostate can make the PSA rise.

The most common non-cancerous cause of elevated PSA levels is benign prostate hyperplasia, more commonly known as BPH. As men age, particularly after age 50, the prostate normally enlarges or grows. The most common symptom with BPH is difficulty urinating. About 80 percent of men will develop some aspect of BPH in their lifetime. BPH is NOT cancer, nor will it lead to cancer, but BPH may cause a false elevation of PSA values.

Another common cause of false elevation of PSA value is prostatitis. Prostatitis simply means "inflammation of the prostate." Prostatitis is very common and usually causes symptoms similar to a bladder infection (burning, frequency and urgency to urinate). Many men with prostatitis, however, have no symptoms. The inflammation from prostatitis causes PSA to leak into the bloodstream and causes the PSA level to be higher than normal. Even a simple rectal exam can cause the PSA to rise somewhat. Ejaculation has been shown to cause an increase in the PSA level in some men for about 48 hours. If possible, the patient should not ejaculate for 48 hours before a PSA test. If ejaculation has occurred and the PSA is elevated, a repeat test might be necessary. What this means is that PSA is NOT a cancer measurement, and that an elevated PSA does NOT mean you have cancer. The only test that will determine the presence of cancer with certainty is a biopsy of the prostate.

Does age have anything to do with PSA levels?

Recent studies have suggested that the 4.0 level may be too high for younger men and too low for older men. Most of the studies for which we have long-term evaluation have used the 4.0 level. Many researchers now use the following levels, although more time is needed to assure that these levels are more accurate than just the 4.0 value.

  • Age 40 - 50 0 to 2.5
  • Age 50 - 60 0 to 3.5
  • Age 60 - 70 0 to 4.5
  • Age 70 - 80 0 to 6.5

What happens if I have an elevated PSA level?

FIRST TIME MEASUREMENT OF PSA (Note: This assumes that the rectal examination found no suspicious nodules or hardness within the gland. Even if one's PSA level is within normal range, a suspicious nodule must be evaluated.)

PSA of 4.0* or less

If your PSA level has been measured for the first time and is less than 4.0, we recommend repeating the test on a yearly basis. (* This number may be dependent on age. See above for normal values.)

PSA between 4.0 and 10

If your PSA is greater than 4.0 but less than 10, we recommend a diagnostic ultrasound of your prostate. If the ultrasound shows no suspicious areas, we will either watch your prostate and prostate specific antigen closely or perform random biopsies taken from various parts of the prostate. If observation alone is used, a repeat PSA should be drawn in four to six months, or no later than one year. If the ultrasound shows a suspicious area, biopsy of the area needs to be done (usually at the time of ultrasound, if you have been prepared with antibiotics).

PSA greater than 10

If your PSA is greater than 10, we recommend a diagnostic ultrasound of your prostate simultaneous with biopsies of the prostate. If the ultrasound shows no suspicious areas, then random biopsies of the prostate are taken. If the ultrasound shows suspicious areas, biopsies of the areas, along with random biopsies, need to be done.

Another way of looking at PSA is to measure "PSA Density." PSA density measures the amount of PSA in the blood relative to the size of the prostate gland. We normally expect that men with a larger non-cancerous prostate will have a higher PSA; the smaller non-cancerous prostate glands will have a lower PSA. We become concerned about patients with PSA values out of proportion to their prostate size. Conversely, a very large prostate with a slightly high PSA might not be so suspicious by density measurements. In other words, the PSA density allows us to pick out suspicious prostate glands that could be missed by PSA levels alone. Many researchers feel density is misleading and do not use it.

'Free PSA'

Another new test is called "free" PSA. PSA that circulates in the serum is usually bound or attached to larger protein substances. The amount of PSA that floats free and unattached is called "free" PSA. The standard PSA measurement is a reflection of all PSA, free and bound. New research suggests that prostate cancer PSA is usually more bound than non-cancerous PSA. The percentage of free PSA to total PSA may give some additional benefits in deciding who to biopsy and who to watch. If the free PSA to total PSA is greater than 23 percent, cancer is more unlikely. If the percentage is less than 10 percent, cancer is more likely. Percentages between 10 percent and 23 percent offer no definite information. Because the free PSA test has not been approved by the FDA, many laboratories do not offer it and your insurance company may not pay for it. It costs about $65 at this time. The free PSA test data is accurate for patients with PSA values between 4.0 and 10. The usefulness of free PSA for values below 4.0 and above 10 has not been established.

If you have had previous measurements of PSA (Note: This assumes that the rectal examination found no suspicious nodules or hardness within the gland. Even if one's PSA level is unmeasurable, a suspicious nodule must be evaluated.) When we have the luxury of previous PSA values, we look at numbers a little bit differently. The PSA level will almost always rise in the face of a cancer that is growing. Any PSA level that is rising is suspicious. As mentioned earlier, the high PSA level may NOT mean that cancer is present. For example, a male with a stable PSA of 8 over a three-year period (8,8,8) is probably at less risk than a male with a PSA of 2, 4, and 6 within the same time frame, even though the value 8 is above all the values of the second patient. The second patient's rising levels suggest growth and this must be considered suspicious for cancer. If the first patient with repeating 8 values had a negative biopsy when first discovered, there may be no need to repeat the biopsies. If his levels jumped to 10 or 15 for no apparent reason, repeat ultrasound and biopsies would be indicated. Recent studies suggest that either a 20 percent rise or a measurable rise of 0.75 in PSA in one year should prompt a closer look and possibly an ultrasound and biopsy.

How often should my PSA be re-tested?

We feel -- as do the American Cancer Society, the American Urological Society and other groups -- that a yearly PSA along with a rectal examination of the prostate should be done in men over age 50. In high-risk groups, such as men with a family history of prostate cancer, screening should start between age 40 and 45. Given a normal and stable PSA, we firmly believe that routine ultrasound of the prostate is not indicated.

We also recognize that many groups feel that PSA screening should not be routinely done. To date, no evidence exists that routine PSA screening saves lives, and many believe that the treatment of prostate cancer might cause more harm than help. Patients need to be aware of the risks of screening and not screening. Please ask us if you have any questions.