Prostate Specific Antigen (PSA): What Every Man Needs to Know

Michael K. Brawer, MD

Today prostate cancer is the most common tumor in American men and the second most common reason for a cancer related death in the United States. There are three ways to change these sobering statistics. We can improve therapies, develop methods of prevention, or improve early detection; improving the opportunity for the diagnosis of cancer at an earlier stage when it is more likely it can be cured.

Prostate Specific Antigen, PSA, is a protein that arises in the prostate but is detectable in the blood stream. It has been shown to be elevated in men with cancer. Its greatest utility is its application in detecting men who are at risk for prostate cancer. That is to say, measuring PSA in healthy men, with or without prostate symptoms (such as difficulty in urinating, getting up at night to void or a slow urinary stream) helps in finding out if indeed they may have prostate cancer.

It is important to emphasize, that an elevated PSA does not mean that a person has cancer. It signifies a risk for having prostate cancer but does not establish the diagnosis. In effect it is not dissimilar from a warning light in your automobile. This does not prove you have a serious problem but it is an indication that things need to be investigated.

As stated above, PSA is made in the prostate where its function is to improve the consistency of the semen for achievement of a pregnancy. Other than that it has no useful role. A small amount of PSA actually can leak from the prostate into areas where it is picked up by the blood stream and thus can be readily measured by accurate laboratory tests. Experts disagree as to what is an abnormal level of PSA. Historically we used a cutoff of 4.0 ng/ml however, more recently most investigators have lowered the cutoff as it has been demonstrated that almost as many men have cancer between a PSA 2.5 to 4.0 ng/ml as do between say a 4.0 and 5.0 ng/ml.

When a man is shown to have an elevated PSA he needs to be evaluated by a urologist who will counsel the patient as to the likelihood of cancer. Factors such as the results of a physical examination (Digital Rectal Examination), family history, race, etc, will come into play. If it is decided that the patient is at sufficient risk of malignancy and that the diagnosis of prostate cancer would be of benefit to the patient be­cause of the potential clinical significance of his cancer, generally an ultra­sound guided prostate needle biopsy is performed. This would provide material for the pathologist (a doctor who specializes in disease) to examine small slivers of the prostate under a microscope to evaluate whether there is cancer. Indeed, a definitive diagnosis of cancer can only be made by examination of tissue.

While a biopsy is generally well tolerated, it does have some potential side effects and will result in minor discomfort. Also it is expensive. Because of this there have been tremendous efforts to try and make PSA more specific and decrease the likelihood of a false positive result. A false positive is a PSA result that is abnormal in the absence of prostate cancer. Utilizing cut­offs of 3.0 or 4.0 ng/ml, more then 2/3 of men will be shown not to have cancer, at least on their first biopsy. We have adjusted PSA for the size of the prostate, for the patient’s age as well as for changes in PSA over time in an effort to lessen the false positive results. Unfortunately, none of these approaches have proven to be useful in the general patient situation.

What has been shown to be useful is the measurement of the so-called free component in conjunction with the total PSA. This does provide approximately 20% to 25% improvement in the test performance by lessening the false posi­tive test result. Unfortunately measure­ment of the free and total PSA doubles the cost of PSA testing. Also the free form of PSA is unstable and this renders the results extremely unreliable.

More recently a new form of PSA has become widely available, the so-called complexed PSA (cPSA). It has been demonstrated that this form of PSA is more specific for men with cancer and measurement of complexed PSA provides all the benefit of the free to total PSA ratio without the doubling of the cost. Moreover, complexed PSA is very stable. When complexed PSA is used the cutoff of 2.2 to 2.5 ng/ml is used as the threshold for normal.

The most important issue to be consid­ered with respect to PSA is whether you should be tested. While it has not been definitively proven that PSA testing saves lives, the data is moving strongly in this direction. Within a few years we probably will know definitively whether this early detection test works and most experts believe that the results will demonstrate that it does. It is incumbent on the individual patient as well as his physician to weigh the pros and cons of PSA testing. If a man has more than a 10-year life expectancy, he probably should be tested. The interval for repeat testing in the face of a normal PSA is not well established, however, it can be stated that the lower the PSA the less likely it is that the man will ever develop cancer. Thus the common practice of annual PSA testing may not be necessary in men that have a total PSA of say less then 1.5 ng/ml or a complexed PSA of less then 1.0 ng/ml.

Undoubtedly, in the future, we will develop new prostate cancer diagnostic tools. For now we are fortunate to have the combination of a PSA and digital rectal exam as recommended by the American Cancer Society and American Urological Society.

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