Prostate Cancer Screening - Prostate Specific Antigen

Prostate Specific Antigen

The PSA test measures the blood level of prostate-specific antigen, an enzyme produced by the prostate. To be specific, PSA is a serine protease similar to kallikrein. Its normal function is to liquify gelatinous semen after ejaculation, allowing spermatozoa to more easily navigate through the uterine cervix.

PSA testing is controversial and may lead to unnecessary, even harmful, consequences in some patients. Since the test was introduced PSA screening in the U.S., more than 1 million additional men there have been diagnosed and treated for prostate cancer, but it has been estimated that the vast majority (more than 95%) of these men receive no benefit from their positive diagnosis. Even if one makes the most optimistic assumption about the benefit of screening (i.e. that the entire decline in prostate cancer mortality observed since the introduction of PSA testing is due to introduction of the test) less than 5% (or one in twenty) of those getting a positive diganosis received any benefit at all from it.

Other research studies, however, point to the success of the PSA test in reducing death due to prostate cancer. The European Randomized Study of Screening for Prostate Cancer (ERSPC) study, published in the New England Journal of Medicine (March 2009), documented that screening resulted in a 20 percent reduction in prostate cancer mortality.

More recent studies have shown greater effectiveness in how screening has reduced the prostate cancer death rate. A study published in the European Journal of Cancer (October 2009) documented that prostate cancer screening reduced prostate cancer mortality by 37 percent. By utilizing a control group of men from Northern Ireland, where PSA screening is infrequent, the research showed this substantial reduction in prostate cancer deaths when compared to men who were PSA tested as part of the ERSPC study.

The risk of prostate cancer increases with increasing PSA levels. 4 ng/mL was chosen arbitrarily as a decision level for biopsies in the clinical trial upon which the U.S. Food and Drug Administration (FDA) in 1994 based adding prostate cancer detection in men age 50 and over as an approved indication for the first commercially available PSA test. 4 ng/mL was used as the biopsy decision level in the PLCO trial, 3 ng/mL was used in the ERSPC and ProtecT trials, and 2.5 ng/mL is used in the 2007 NCCN guideline.

PSA levels can change for many reasons other than cancer. Two common causes of high PSA levels are enlargement of the prostate (benign prostatic hypertrophy (BPH)) and infection in the prostate (prostatitis). It can also be raised for 24 hours after ejaculation and several days after catheterization.

PSA levels are lowered in men that use finasteride (Proscar or Propecia) or dutasteride (Avodart) to treat BPH. After a year, finasteride was shown to lower PSA levels by 50% or more. Finasteride is also marketed as Propecia (1 mg.) for baldness, and the lower dose was shown in a further clinical trial to also lower PSA readings by 50% after a year. As a result, reference ranges and calculations of the rate of change in PSA levels per year must be adjusted accordingly in men taking such drugs.

Several other ways of evaluating the PSA have been developed to avoid the shortcomings of simple PSA screening. The use of age-specific reference ranges improves the sensitivity and specificity of the test. The rate of rise of the PSA over time, called the PSA velocity, has been used to evaluate men with PSA levels between 4 and 10 ng/ml, but it has not proven to be an effective screening test. Comparing the PSA level with the size of the prostate, as measured by ultrasound or magnetic resonance imaging, has also been studied. This comparison, called PSA density, is both costly and As of 1994 is not considered to be an effective screening test. but does have prognostic value. PSA in the blood may either be free or bound to other proteins. Measuring the amount of PSA which is free or bound may provide additional screening information, but questions regarding the usefulness of these measurements limit their widespread use As of 2000.