Prostate Screening: Refining What PSA Levels Mean
From Johns Hopkins Medical Letter - October, 2007
Since the prostate specific antigen (PSA) test became widely used in the 1990s, prostate cancer deaths have dropped dramatically. Today one of the biggest problems with PSA testing is that it detects many cancers that are not life threatening and would never have been diagnosed or treated otherwise, especially among older men. H. Ballentine carter, M.D. Professor of Medicine, director, Adult Urology, The Johns Hopkins Hospital, and Health After 50 Board Member, discusses current trends in PSA testing that may reduce overdiagnosis and overtreatment of prostate cancer.
How des PSA testing resulting in overdiagnosis and overtreatment?
PSA levels are most often elevated for reasons other than cancer, such as prostatic enlargement (benign prostatic hyperplasia) or prostatic inflammation, which are common among aging men. In addition, many men with these conditions also have small prostate cancers that are also common with age but usually do not progress. The PSA test cannot differentiate between dangerous cancer and benign conditions, so when biopsies are based on elevated PSA test results, prostate cancer are often found serendipitously; many of these would not have been found otherwise.
This overdiagnosis of prostate cancer has been estimated to occur in 30-50% of men between ages 55 and 80 years. Over 85% of prostate cancers detected are treated when diagnosed. Thus, overtreatment of cancers that would not have caused harm is a byproduct of screening.
The extent to which PSA testing for the early diagnosis of prostate cancer results in more benefit (reduction of prostate cancer deaths) versus harm (detection and treatment of prostate cancers that would not have caused harm) is hotly debated. Nevertheless, physicians and patients prefer the risk of unnecessary treatment to missing a potentially lethal cancer.
The solution to the dilemma is a test that can differentiate between life-threatening and indolent prostate cancer before a biopsy takes place.
In the meantime, how are doctors trying to reduce the number of needle biopsies and over diagnosis?
Currently, annual PSA testing beginning at age 50 is recommended, but newer guideline PSA test at age 40, another one at 45, and then an annual or biennial PSA test beginning at age 50 depending on the PSA level.
By starting to accumulate a PSA history at age 40, a man will have measurements to compare with levels obtained in his 50s in order to determine the rate his PSA change — his PSA velocity — a useful measure of the presence of a life-threatening cancer.
PSA levels vary a lot over the short term (6 months). It is important to have a PSA history of more than 2 years to evaluate PSA velocity accurately. If PSA velocity is consistently above 0.4 ng/mL per year in a man with a PSA level below 4.0/ng/mL, prostate cancer should be suspected and a biopsy considered. In men with PSA levels between 4 and 10 ng/mL, a PSA velocity of 0.75 ng/mL per year suggests the presence of cancer.
Is there a reliable PSA cutoff?
In the part, doctors relied more heavily on a standard PSA cutoff of 4.0 ng/mL to determine when a biopsy should be done, but no absolute cutoff point is accurate for everyone. Other risk factors we need to know about include a history of prostate cancer on both parents’ sides and race-black men are at much higher risk for developing prostate cancer, particularly life-threatening prostate cancer.
Age is a also very important. A younger man might be at much higher risk for harboring cancer than an older man with the same PSA level. Younger men are less likely to have a PSA elevation due to prostate enlargement.
Are you ever old enough to stop getting a PSA test?
This is a very difficult question that no one has adequately addressed. If a man is over 70 and in poor health owing to another illness or condition, a PSA test may not be necessary since it’s unlikely that he will die of prostate cancer. On the other hand, it may make sense for a healthy 70-year-old to continue with PAS testing. If a man has maintained a very low PSA throughout his life (e.g., below 3.0 ng/mL), he may not need testing after age 75.
What other tests besides PSA are currently under exploration?
Robert Getzenberg, M.D., Director of Research at the Brady Urologicial Institute at Johns Hopkins, discovered a protein (early prostate cancer antigen, or EPCA) that is present in the blood in higher amounts in men with prostate cancer than in men without it.
EPCA appears to be more prostate-cancer specific than PSA, and the test could reduce unnecessary biopsies and, possibly, overdiagnosis and overtreatment of prostate cancer. More work is needed to determine the value of this test for early detection.
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