Role of drugs in prostate cancer prevention comes into focus

San Francisco-There is growing evidence that finasteride (Proscar) can prevent the clinical manifestation of prostate cancer and increase the diagnostic accuracy of PSA testing. Other forms of chemoprevention may find even wider use if early data suggesting that prostate cancer is an infectious disease are supported.

"Chemoprevention of prostate cancer is an attractive prospect," Eric Klein, MD, professor of surgery at the Cleveland Clinic Lerner College of Medicine, told colleagues at the first annual Urology Congress here.

"It is better to never be diagnosed with disease than to be diagnosed, followed by treatment with significant side effects. Results from the Prostate Cancer Prevention Trial [PCPT] show that finasteride reduces the risk of prostate cancer by 25%."

The actual finding that finasteride lowers the risk of prostate cancer by 25% is not new. But the initial analysis that showed an overall 25% risk reduction in the finasteride arm also showed a 25% increase in the incidence of high-grade tumors. More detailed analysis suggests that the increase may be due to ascertainment bias, not an actual increase in the incidence of high-grade disease.

Because finasteride treatment reduces the size of the prostate by about 25%, biopsy needles are correspondingly more likely to sample any high-grade tumors that are present.

"If you do the same number of biopsies in a smaller gland, it stands to reason that you will find more cancers," Dr. Klein told the audience. "The data support that conclusion."

Furthermore, use of finasteride increased the diagnostic accuracy of PSA for finding high-grade disease in the PCPT. Together, these phenomena may explain the increased incidence of high-grade disease in the finasteride arm, although a true biologic effect of finasteride cannot be excluded.

Delaying development

The use of pharmacologic agents to prevent prostate cancer is a relatively new concept, Dr. Klein noted, but chemoprevention is an established paradigm. Tamoxifen (Nolvadex, Soltamox) is used to prevent breast cancer, fluoride is used to prevent dental cavities, statins are used to prevent myocardial infarction, and estrogens and bisphosphonates are used to prevent fractures. The mechanisms of actions differ, he explained, but the basic strategy is the same: delay or prevent the development of clinical disease by interrupting key biological processes.

Finasteride's most obvious effect in the prostate is to reduce the size of the gland, the reason it is typically prescribed for BPH. An unexpected benefit from the drug is a 10% improvement in the diagnostic accuracy of PSA. Simply putting a patient on finasteride should reduce PSA by about 50%, Dr. Klein explained. If there is no PSA drop after initiation, or if PSA shows any increase during therapy, the prostate should be biopsied.

Despite the clinical advantages of finasteride, chemoprevention is an off-label use, Dr. Klein noted. Off-label use can complicate third-party payment for a drug that remains a financial burden for many patients.

The sexual side effects of the drug are overrated, Dr. Klein said, citing data showing that the sexual effects of finasteride are minor and similar to age-related changes in sexual activity.

How long finasteride will remain the sole chemoprotective agent for prostate cancer is unclear. Retrospective data suggest that the use of any statin reduces the incidence of prostate cancer by 51%, but no prospective data exist yet, Dr. Klein said.

Slowing chronic inflammation

Emerging models of prostate cancer may also bring chemoprevention into standard practice. Several investigators have suggested that chronic inflammation of the prostate as a result of diet, infection, environmental factors, corpora amylacea, or urine reflux play a key role in the etiology of prostate cancer. If an inflammatory pathway can be confirmed, dietary changes and anti-inflammatory agents might slow or block the emergence and development of prostate cancer.