Two recent studies have further kindled a running debate in the scientific community regarding the use of prostate-specific antigen (PSA) test results, highlighting uncertainties in their interpretation and appropriate response. As a result, some experts are urging patients to discuss with their doctor their overall risk of prostate cancer, including family medical history, to help interpret their PSA results and determine the best course of action.

A study published in a recent issue of the New England Journal of Medicine supports concerns that PSA testing using the generally accepted reference range does not detect all cases of prostate cancer among men who are screened. The study gives new impetus to arguments for lowering the reference range for PSA screening, although opponents maintain that crucial data on the effect of such a change on patient outcomes, including mortality rates, are still missing.

There has been and remains disagreement about the appropriate cut-off for the PSA test above which a biopsy should be performed. If it is set too high, cancers may be missed; if it is set too low, unnecessary procedures may be performed, which can have serious health consequences for the patient, including possible impotence and incontinence. Finding the right middle ground has proven to be a challenge. Two fundamental uncertainties remain at the heart of the matter: (1) whether the additional cancers picked up by lowering the threshold would actually be life-threatening tumors that would require treatment; and (2) whether those patients whose cancers are detected at lower PSA levels would actually have better health outcomes in the long run.

In the current study, researchers examined close to 3,000 men ages 62-91 from the placebo group of a large prostate cancer prevention trial who had never had a PSA level greater than 4.0 ng/milliliter or an abnormal digital rectal exam (DRE). At the end of the seven-year trial, the patients’ PSA levels were measured and they underwent a prostate biopsy. Using the PSA and biopsy data, researchers in the current study found that 15% of the patients had prostate cancer, and prevalence of the disease increased with the PSA level. In fact, 25% of the prostate cancers detected among the patients with PSA levels of 3.1-4 ng/milliliter were aggressive (high grade) cancers. The researchers concluded that prostate cancer can and does occur among men who have PSA levels below the threshold usually considered to be normal.

Findings from another recent study published in the Journal of the American Medical Association start to address one of the underlying questions – the impact of non-treatment of early-stage prostate cancers, about which currently little is known. A sample of 223 patients with early-stage prostate cancer were followed but not treated other than for symptomatic relief if progression occurred. Researchers found that although most of the cancers were slow-growing and did not cause problems during the first 10 to 15 years after diagnosis, after that time there was a negative impact on survival and quality of life. Consequently, they concluded that radical treatment even of early-stage prostate cancers would be warranted, particularly among men with a life expectancy greater than 15 years.

These new studies highlight the latest in the ongoing discussion about the value of PSA testing and suggest some questions that patients should take to their doctor to better understand their own risks and proposed treatments. For more information, see the Related Pages below.

Sources:
Stein, Rob. Widely Used Test Often Misses Prostate Cancer, Researchers Report. Washington Post (A1, A6) May 27, 2004.

Thompson, IM et al. Prevalence of Prostate Cancer Among Men with a Prostate-Specific Antigen of <4.0 ng per Milliliter. The New England Journal of Medicine, May 27, 2004. Volume 350, pages 2239-46.

Carter, HB. Prostate Cancers in Men with Low PSA Levels – Must We Find Them? (Editorials) The New England Journal of Medicine. May 27, 2004. Volume 350, page 22.

Johansson, J et al. Natural History of Early, Localized Prostate Cancer. Journal of the American Medical Association. June 9, 2004. Volume 291, pages 2713-2719.