What is Free PSA? PSA (Prostate Specific Antigen) is a molecule produced by the normal prostate and secreted in large amounts in the male semen, but is also normally present in minute quantities in the male bloodstream. It is now well known and accepted that PSA levels in the blood are elevated by several disease processes in the prostate, most importantly by prostate cancers. PSA's natural location and function is to be in the male semen. It is perhaps only by accident that a tiny amount enters the bloodstream, where it serves no known purpose or function. While in the bloodstream, the PSA is typically bound or "complexed" by a variety of protective blood proteins which inactivate the PSA molecule. Thus, under any circumstances, most of the PSA in a mans blood can be referred to as bound or complexed PSA.
A majority of the total PSA molecules in a man's blood are not bound by blood proteins. This percentage of unbound or uncomplexed PSA is typically referred to as "free PSA". The standard PSA blood tests which are now in widespread use try to measure all of the PSA in a man's blood, or the "total PSA", which includes both bound and unbound molecules.
Over the last few years, several investigators have proposed that a separate measurement of the free PSA in a man's blood, and specifically comparing the percentage of free PSA to the total PSA level in the blood, may provide uniquely useful information to assist in the clinical diagnosis of prostate cancer. Now, commercial assays are available so that free PSA levels can be readily obtained by your doctor if he or she feels they will be helpful in your care.
The proposed utility of free PSA measurements lies in the fact that, for reasons that are not yet fully understood, PSA molecules in men with prostate cancer are more likely to be bound or complexed by protective blood proteins. In other words, the percentage of free PSA in the bloodstream is on average even lower in men with prostate cancer than in men with other benign conditions which can also cause the total PSA levels in the blood to be elevated. The most common benign condition which might do this would be bengin prostatic hyperplasia (BPH).
In clinical practice, free PSA is now being introduced and studied as an additional tool to help decide which men need more aggressive evaluation to check for prostate cancer, including a prostate biopsy, and which men might be safely managed with observation including serial exams and PSA tests over time.
In men presenting with a high standard total PSA test ( over 10) or with a suspicious digital rectal examination of the prostate, there is no recognized utility for obtaining an additional free PSA test. In most such cases, prostate biopsy is indicated to rule out cancer.
Free PSA has been proposed as a secondary test in men with a slight elevation or abnormality of the standard total PSA level, who otherwise have no suspicion of prostate cancer on their physical exam, and who perhaps have an enlarged prostate (BPH) which might also cause a mild elevation of the PSA levels above normal. If the percent PSA compared to the total PSA is high in such an individual, several preliminary clinical studies have suggested that it might be safe to avoid a biopsy of the prostate. This might be particularly beneficial in patients in whom prostate biopsy is technically difficult, such as those who are on medical anticoagulation ( blood thinners ) for a variety of cardiovascular problems, or the man whose rectum has been surgically removed because of rectal cancer. It should be emphasized throughout this discussion that the proper use of free PSA is still a matter of scientific study and debate. Any man with an abnormally elevated standard PSA test but a "normal" percent free PSA who chooses, after careful consideration with his physician, to avoid a prostate biopsy, should have careful medical observation, including repeat PSA tests and prostate exams done on a regular basis.
Another proposed use of free PSA levels is to determine which men with a "high normal" standard total PSA value should undergo prostate biopsy. The normal range for most commonly used standard PSA tests today is 0-4. Yet it is known that a certain number of men with a normal PSA still harbor a cancer in their prostate. This is perhaps particularly true of men with normal but "high normal" ( range 3-4 ) PSA tests. Younger men with "high normal " PSA values as well as men with a strong genetic predisposition to develop prostate cancer ( including those with close male relatives with prostate cancer and all African- American males) whose PSA falls into this "high normal" range may specifically benefit from additional clinical scrutiny. Determination of the percent free PSA in these individuals may help select those at greatest risk ( those with a suspiciously low percent PSA) who would benefit from biopsy sampling of their prostate to check for cancer, despite a normal standard PSA test.
POINTS TO REMEMBER
In patients who are already diagnosed with prostate cancer, there is no recognized advantage to examining percent free PSA in addition to the standard total PSA determination. The only proposed uses of percent free PSA are to assist men and their physicians in screening for and making the initial diagnosis of prostate cancer.
If you are found to have a palpable abnormality on digital rectal examination of your prostate, a biopsy is probably initiated regardless of the results of standard PSA or percent free PSA tests.
Free PSA tests cost more that the standard PSA tests
Much remains to be learned about the percent free PSA levels, including the exact percentage of free PSA compared to total PSA which should be considered as the cutoff point to be called abnormal or suspicious for malignancy or conversely, percentages which can safely be considered "normal or non suspicious". In addition, different commercial assays may yield different cutoff values for percent free PSA because of different methodologies employed.
In a recent review of percent free PSA application and clinical usage, a panel of experts concluded that "caution should be used in interpreting the current literature and individual percent PSA values in clinical practice."