Selenium and vitamin are E not promising, but both the Prostate Cancer Prevention Trial and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial showed a 20% to 25% reduction in the incidence of prostate cancer from two different 5-alpha-reductase inhibitors, finasteride (Proscar) and dutasteride (Avodart).
San Francisco-There is no doubt about the risks of prostate cancer. There are approximately 186,000 new cases of the disease and 29,000 deaths annually in both the United States and Europe. But there are significant doubts about the benefits of population screening for prostate cancer.
In the United States, screening itself roughly doubles the risk of being diagnosed with prostate cancer. Most men who are found to be at risk opt for treatment, even though 90% of them could live out their lives free of clinically important prostate tumors. Thus, prostate cancer chemoprevention has become the focus of intense research efforts.
"Except for selenium and vitamin E, there is no level 1 evidence to support these [prevention] claims," Dr. Klein said. "We can say confidently that neither selenium nor vitamin E are beneficial in preventing prostate cancer or on any health outcome that was examined in SELECT."
At the same time, both the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial showed a 20% to 25% reduction in the incidence of prostate cancer from two different 5-alpha-reductase inhibitors, finasteride (Proscar) and dutasteride (Avodart). PCPT showed that finasteride reduces the likelihood of any cancer and does not promote high-grade cancers. REDUCE showed similar results for dutasteride.
In March, GlaxoSmithKline announced that it re-submitted to FDA its supplemental new drug application for dutasteride for prostate cancer risk reduction among men at increased risk of developing the disease.
"We have level 1 evidence from two different trials," Dr. Klein pointed out. "These 5-alpha-reductase inhibitors are effective cancer preventatives. The question becomes, who do these agents work for?"
The data indicate that both agents show the same relative risk reduction across all risk groups regardless of age, race, or family history and independent of baseline PSA, he said. A quality of life study conducted in conjunction with PCPT showed a 3% reduction in patient sexual activity scores over 7 years. Dr. Klein said that while the reduction is statistically significant because of the large sample size, it is not clinically significant. In REDUCE, erectile dysfunction was the most commonly reported side effect, but the reported incidence was not statistically significant.
"This should not be a reason to not use these agents," he said. "We should tell men they can take one of these agents and get a 25% reduction in the risk of prostate cancer and if there are sexual side effects, you'll have to decide which is more important to you. The use of 5-alpha-reductase inhibitors is an effective primary prevention strategy."
Which men should use these chemoprotective agents? Men who are either at risk of dying of prostate cancer or who are at risk of suffering the consequences of treatment for the disease are appropriate candidates, Dr. Klein said. That means men with elevated PSA.
A new PSA paradigm
Dr. Klein suggested resetting the PSA paradigm following the 2009 release of an AUA best practice statement calling for earlier PSA testing. Multiple studies show that a baseline PSA of 1.5 ng/mL or higher is an accurate predictor for future prostate cancer. Other trials suggest individuals whose PSA is tested between the ages of 44 and 50 years and found to be higher than the population mean have a 10% or greater lifetime risk of developing prostate cancer. Men with a PSA of 1.2 to 1.3 ng/mL, who represent 30% to 40% of most urologic practices, are good candidates for chemoprevention.
"We need to pay better attention to PSA," Dr. Klein concluded. "We need to identify groups of individuals who are at high risk who need to be biopsied and treated; those at intermediate risk who are great candidates for risk reduction; and individuals at low risk who do not need further intervention."
Dr. Klein has received honoraria from GlaxoSmithKline.