Yes or no to PSA screening: Four issues need resolution

Key Points

In a special lecture at the Prostate Cancer Symposium here, Dr. Schröder listed four questions that must be answered before prostate cancer screening becomes health care policy:

Major ongoing studies are attempting to resolve these questions. The two largest are the European Randomised Study of Screening for Prostate Cancer (ERSPC), which has enrolled more than 250,000 men and has a follow-up greater than 6 years; and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a U.S. study that has enrolled 154,938 men and women age 55 years and older and that needs a follow-up of 13 years, to be reached in 2013.

"The potential harm of screening lies mainly in the effect of treatment for those men who are over-diagnosed, an inherent problem when screening for any disease," Dr. Schröder said. "Within ERSPC, over-diagnosis has been estimated to occur in 50% to 60% of cases, depending on age groups and screening technology.

"Next to the unnecessary treatment of indolent cases, the quality of life issue is determined by the effects of screening itself, as well as by the effects of treatment. These concerns must be balanced against the amount of suffering that occurs in men not treated early if screening were proven to prevent the sequelae of prostate cancer."

Dr. Schröder is concerned that the true sensitivity and specificity of PSA in prostate cancer screening has been unknown until recently. The Prostate Cancer Prevention Trial has found that large proportions of cancers-often potentially aggressive cancers-are undetected with currently used PSA cut-off values, which vary between 2.5 ng/mL and 4.0 ng/mL.

"Lowering the cut-off values may lead to an unacceptable number of biopsies and degree of over-diagnosis, as seen recently in a study that calculated the epidemiologic consequences of performing biopsies for all men in the United States with a PSA of more than 2.5 ng/mL," Dr. Schröder noted.

Opportunistic screening and population-based screening must be differentiated, he said, as the value of screening is uncertain primarily because a significant effect of screening on prostate cancer mortality has not been seen to date. Dr. Schröder expects definitive answers within the next few years. In the meantime, men who wish to be screened must be carefully informed about the advantages and disadvantages of early detection, preferably with validated information.

"Over-treatment is the main factor that will eventually influence quality of life-adjusted years, even if a significant advantage in survival could be shown," Dr. Schröder said. "Fortunately, over-diagnosis in screen-detected cases can be reduced by about 30% through the application of nomograms identifying indolent cancer. Data from ERSPC show that it is not necessary to diagnose all prostate cancer cases that initially present with low PSA values. More than 95% of these cases can still be considered curable if diagnosed 4 and 8 years later."

Advising patients

Pending the outcome of the ERSPC and PLCO studies, Urology Times asked Dr. Schröder how he would advise his patients about whether to pursue PSA testing.

"In a situation of uncertainty, it is not possible to forbid the use of a test that potentially can prevent death from prostate cancer. However, those men who decide to be tested take a risk. They may be treated for no good reason, and treatment complications may be unnecessary in any given situation. As I have shown, the situation of over-treatment can be predicted in about 50% of screen-detected cases," he said.

"In my view, opportunistic screening should only be applied to men who are completely informed about the potential risks and benefits and who can make a conscious decision on that basis. Once this information has been supplied and discussed by a professional and a given man decides to be screened, this screening should be applied with the maximum possible care."