PSA is a protein manufactured in the prostate and virtually no other organ. Women, who do not have prostates, do not have detectable levels of PSA, generally.  PSA is the enzyme responsible for liquifaction of semen a few minutes after it has clotted. The prostate glands manufacture this protein in large quantities.

Imagine that you are looking at  a single normal prostate gland tubule cut in cross section. The cells lining the center, or lumen, manufacture prostate secretions including PSA. There is also a circle around the cells, called the basement membrane, which stops PSA and other secretions from entering the blood stream.

All of your glands, your intestines, and your urinary tract are organized the same way: a secreting or absorbing layer of cells with a basement membrane to keep a tight separation between the inside and the outside. That is how the prostate makes a lot of PSA but only a tiny amount normally is found in the blood. This is what we are measuring with the PSA test.

What causes abnormal PSA levels?

Please understand that the prostate gland cells (the epithelium) are manufacturing PSA. The cells will continue to manufacture PSA if they are in locations outside the prostate. PSA levels in the blood go up if the barrier between the epithelium and the bloodstream is damaged. The three typical sources for damage are: cancer, bacterial infection, and prostate infarction or destruction of part of the prostate by damage to its blood supply.

Minor elevation of the PSA levels is sometimes due to cancer, but normally a little PSA leaks from the prostate into the blood. If the prostate is enlarged then the leakage appears exaggerated. This is probably why the PSA can be slightly abnormal in men with enlarged prostates who do not have cancer. Trauma to the prostate, as by physicians performing prostate massage, and sex might also cause minor transient elevations of PSA.

The PSA level in the blood can vary by about 20% from day to day. Nevertheless, the data are clear that a single abnormal PSA value puts one in the higher group for prostate cancer. Now that we know the test can be falsely elevated by trauma, infections, and intercourse, we inquire after these factors before accepting the validity of the blood test.

How does PSA assist cancer treatment?

Before getting into the complicated business of how we use PSA in cancer detection, it is helpful to understand its use in monitoring cancer treatment. Since only prostate cells make PSA, a successful radical prostatectomy should result in an undetectable PSA level. Actually, nothing is ever that simple.  It is possible to leave benign glands at the bladder neck during prostatectomy. This can result in a low level of PSA production.  Also, tiny quantities of PSA are made in some accessory glands along the urethra.

PSA is a good marker for the success of surgery. If we remove a patient’s prostate and all of the cancer was inside, then the PSA should go to very low levels. If some cancer cells had escaped from the prostate, then the PSA will remain measurable or become measurable and continue to rise after a few years. As a practical matter, PSA readings over 0.5 usually indicate residual or recurrent cancer following radiation or surgery.

How do we use PSA for diagnosis of prostate cancer?

PSA is reported in terms of nanograms of protein per milliliter of serum (ng/ml). The scale is open-ended. Men with advanced and widespread prostate cancer can have PSA readings over 2,000 ng/ml. The assay is performed using labelled antibodies on a serum sample. The test is run most days. You do not have to fast for this blood test.

What is the role of free PSA?

Scientists and physicians have been trying to make the PSA test even more useful for several years. Most of these attempts (PSA density, PSA velocity, age dependent PSA ranges) were impossible to verify and were not very useful. Free PSA, however, is both reproducible and useful. Free PSA is that percentage of the total PSA which circulates in the blood without a carrier protein.

The point here is that patients with free PSA below 7% usually have prostate cancer. They should undergo biopsy. If biopsy is negative they need repeat biopsies at frequent intervals if the free PSA is reproducibly low. Patients with free PSA over 25% usually have benign prostate hyperplasia. These patients are often told to undergo a single ultrasound and biopsy session. As a single session is about 85% accurate in finding prostate cancer these patients have a residual risk after biopsy of less than 3%. Therefore, they need their blood rechecked annually but do not require repeat biopsy evaluation unless the free PSA starts to fall or the total PSA continues to rise, which would imply interval development of a cancer.  Consult with your doctor on this.