New prostate-specific antigen guidelines to tackle controversial issues

November 1, 2008

The 2008 update of the American Urological Association clinical guidelines for prostate-specific antigen screening will build on the 2000 version while addressing some controversial aspects of screening.

Issues under discussion include age- and race-specific screening, the optimal threshold PSA value to trigger a biopsy, and the possible role of PSA velocity and other alternatives to absolute values in assessing prostate cancer risk.

"PSA screening remains controversial," guideline committee member Kirsten L. Greene, MD, assistant professor of urology at the University of California, San Francisco, said at a plenary session during the AUA annual meeting in Orlando, FL. "There is no level-1 evidence showing a survival benefit with PSA screening for prostate cancer."

On the other hand, the absence of a clear-cut survival benefit is accompanied by concern that overdetection may lead to overtreatment of indolent disease and treatment-related morbidity. The line-up against PSA screening includes the U.S. Preventive Services Task Force, the American College of Preventive Medicine, the American Medical Association, and the American College of Physicians.

Two large, ongoing studies, one in the United States and one in Europe, will provide the first level-1 evidence regarding the usefulness of PSA screening, she added. Until the European Study of Screening for Prostate Cancer and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial are completed, "guidelines will be based on available evidence and consensus expert opinion."

Comparing 2000, 2008 guidelines

The 2000 version of the guidelines recommended that routine screening begin at the age of 50 years. The 2008 working committee is considering whether the starting age should be lowered to 40 years for all men who want to be screened.

Regarding the PSA level that warrants a biopsy, the current AUA document recommends a threshold of 4.0 ng/mL, and the National Comprehensive Cancer Network recommends 2.5 ng/mL. Dr. Greene said her committee is studying the concept of a continuum of risk, which holds that no detectable PSA level is safe-a concept that evolved from the Prostate Cancer Prevention Trial (PCPT).

As opposed to an absolute PSA value, PSA velocity reflects the protein's behavior. Whether behavior trumps level is another thorny issue taken up by the guideline committee.

Use of age- and race-adjusted PSA values also has supporters and detractors, Dr. Greene added. The 2000 AUA guidelines recommended consideration of an earlier age for the start of routine screening in African-American men. Critics argue that the approach is more sensitive for younger men, leading to overdetection, and biased against older men, leading to delayed diagnosis.

Arguments have been made for and against various PSA isoforms for routine screening, including free and total PSA, complexed PSA, and isoforms combined with PSA density. The committee has weighed the evidence and will render a verdict in the near future, said Dr. Greene.

Similarly, the contributions of prostate volume to PSA values and dynamics underwent scrutiny, as did the potential value of incorporating risk stratification tools, such as nomograms and the risk calculator used in the PCPT.

The guideline update has reached final peer review, one of the last steps in the development, revision, and approval of the document.

"Our goal was to build upon existing guidelines by including new information, addressing the screening controversy, and finding ways to better risk stratify patients for biopsy," said Dr. Greene.