PSA and Its Derivatives

By Plaut, David | Journal of Continuing Education Topics & Issues, August 2008 | Go to article overview

PSA and Its Derivatives


Plaut, David, Journal of Continuing Education Topics & Issues


Since PSA was last reviewed for this publication, more work has been done that clarifies some of the questions. Others remain unanswered and some heatedly discussed.

To review PSA and prostate cancer quickly, here is a list of some important points:

* Prostate cancer (PCa) is the second leading cause of death (after coronary heart disease) in U.S. males.

* PCa can often be detected with a serum measurement of prostate specific antigen (PSA) and/ or

* a digital rectal examination (DRE), although neither is highly sensitive (positive in disease) or specific (negative in the absence of disease).

* Most cases of PCa occur in men older than 60 and is a slow growing cancer. Because of these two factors, there continues to be discussion of whether screening of the general male population should be carried out. (Many organizations and entire countries oppose such screening--WHO, Canada and most of Europe). Debate persists as to whether treatment of PCa that is unlikely to be the cause of death should be treated. All this is not to say that physicians should not apprise their patients of the consequences and treatment of PCa as well as the pros and cons of measuring PSA.

* Other assays derived from PSA have been proposed including reference intervals based on age, PSA velocity, and PSA density, other forms of PSA--complexed PSA and free PSA. Some other assays are still in the research phases--PSA RNA and ultrasensitive PSA.

In this update, I have chosen to concentrate on PSA velocity and the utility of screening.

PSA Velocity (change/year)

In a preventive medicine study in Sweden, 4,907 men aged at last 49 years gave two blood samples about six years apart. (Ulmert et al.) Free (fPSA) and total PSA (tPSA) were determined in archived plasma samples. PCa was diagnosed in 9% of the men. The median time from second blood draw to cancer diagnosis was 16 years (thus at age 65). The difference between tPSA level at second assessment and the first was associated with prostate cancer as was the tPSA. (This change in PSA is usually termed PSA velocity and is usually measured with two tPSA assays a year apart. The usually accepted change is 0.7 ng/mL per year.) Although PSA velocity is significantly increased in men with prostate cancer up to two decades before diagnosis, PSA velocity adds to the diagnosis of PCa.

This same group studied 21,277 men aged up to 50. Through 13 years of follow up, 498 (2.5%) were diagnosed with PCa; of these, 161 had locally advanced or metastatic prostate cancers. Levels of tPSA and free PSA were associated with the severity of the disease. The authors concluded that "a single PSA test taken at or before age 50 is a very strong predictor of advanced prostate cancer diagnosed up to 25 years later. This suggests the possibility of using an early PSA test to risk-stratify patients so that men at highest risk are the focus of the most intensive screening efforts." This study also noted that while "PSA velocity is significantly increased in men with prostate cancer up to two decades before diagnosis, it does not aid long-term prediction of prostate cancer."

In contrast to this conclusion, a group from Johns Hopkins stated that the PSA velocity is significantly higher in men of all ages with prostate cancer compared with men with no prostate cancer. Their data indicated that the "median PSA velocity in men with prostate cancer was less than 0.75 ng/mL/year regardless of age, suggesting that this threshold may be too high." Thus, a number of patients with PCa had a PSA velocity well within the acceptable range. Averages do not address the individual patient.

Sun and his group from Duke University found that the prevalence of prostate cancer was 4.4% for men aged less than 50 years and 14.2% for those 50 and older. They did not present data on the mortality of these groups (treated or untreated). It is well known that the prevalence of PCa increases with age, just as it is well known that many men die with prostate cancer but not from prostate cancer.

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