Prostate-Specific Antigen: To Test and Test and Test Again? Or Should We Test at All?

Abstract & Commentary

Synopsis: An isolated elevation in PSA level should be confirmed several weeks later before proceeding with further testing, including prostate biopsy.

Source: Eastham JA, et al. JAMA. 2003;289:2695-2700.

Serum prostate-specific antigen (PSA) testing is frequently used in early detection programs for prostate cancer. While PSA testing has resulted in an increase in prostate cancer detection, its routine use has been questioned because of a lack of specificity. The objective of this study was to determine whether year-to-year fluctuations in PSA levels are due to natural variation and render a single PSA test result unreliable.

The main outcome measure was an abnormal PSA test result based on a PSA level higher than 4 ng/mL; a PSA level higher than 2.5 ng/mL; a PSA level above the age-specific cutoff; a PSA level in the range of 4-10 ng/mL and a free-to-total ratio of less than 0.25 ng/mL; or a PSA velocity higher than 0.75 ng/mL per year.

Prostate biopsy would have been recommended in 207 participants (21%) with a PSA level higher than 4 ng/mL; in 358 (37%) with a level higher than 2.5 ng/mL; in 172 (18%) with a level above the age-specific cutoff; in 190 (20%) with a level between 4 and 10 ng/mL and a free-to-total ratio of less than 0.25 ng/mL; and in 145 (15%) with a velocity higher than 0.75 ng/mL per year.

Among men with an abnormal PSA finding, a high proportion had a normal PSA finding at 1 or more subsequent visits during a 4- year follow-up: 68 (44%) of 154 participants had a PSA level higher than 4 ng/mL; 116 (40%) of 291 had a level higher than 2.5 ng/mL; 64 (55%) of 117 had an elevated level above the age-specific cutoff; and 76 (53%) of 143 had a level between 4 and 10 ng/mL and a free-to-total ratio of less than 0.25 ng/mL.

Eastham and colleagues concluded that an isolated PSA level should be confirmed several weeks later before proceeding with further testing, including prostate biopsy.

Comment by Ralph R. Hall, MD, FACP

This information clouds the use of the PSA even further. When I have 2 tests for the same condition, 1 positive and 1 negative, which one do I believe? I usually do a third test hoping to get some consistency in the results. But, how do I interpret the third test result with this information?

Measurement of the serum PSA in combination with the digital rectal examination has been used for the detection of early prostate cancer for more than 10 years. Eastham et al note that at present PSA testing is not recommended as a screening test by the United States Preventative Disease Task Force or by the Canadian Task Force on Preventative Health Care. The National Cancer Institute defines the PSA as a strategy that is under investigation.

If we use the information from this study to reduce the number of costly prostate biopsies, will we raise the cost in terms of morbidity and mortality? We do not have these data; so what do we do? One of my colleagues, an oncologist, advocated watchful waiting until he was diagnosed with prostate cancer after a suspicious rectal examination. His Gleason scores were less than 7. He opted for aggressive therapy for his cancer.

Now we read that prostate cancer might be prevented by using finasteride.1 This will likely result in our having to evaluate PSA level changes in many patients taking finasteride for prevention. What do we know about PSA levels under these conditions?

Combining the digital rectal examination with 2, and perhaps 3, PSA determinations may still be a reasonable approach until we have better data or better tests. Some physicians will undoubtedly avoid this approach. Patients will have to know and understand the current data and to participate in an active manner in the decisions that are made. The circumstances really haven’t changed, have they?

I am reminded of a verse from the Rubaiyat of Omar Khayyam:2

Myself when young did eagerly frequent
Doctor and saint, and heard great argument
About it and about: but evermore
Came out the same door as in I went
.

Dr. Hall, Emeritus Professor of Medicine, University of Missouri-Kansas City School of Medicine, is Associate Editor of Internal Medicine Alert.

References

1. Thompson I, et al. N Engl J Med. 2003;349:215-224.

2. Khayyam R. Rubaiyat of Omar Khayyam. Philadelphia, Pa: Running Press Book Publishers; 1989.

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