Clinical Practice Guidelines

Online Exclusive - March 25, 2009

In February 2009, the Journal of Clinical Oncology (JCO) published the ASCO/American Urological Association (AUA) Clinical Practice Guidelines with recommendations on the use of 5-Alpha Reductase Inhibitors (5-ARIs) for chemoprevention of prostate cancer; the Journal also provided an update on the ASCO guideline on the use of chemotherapy and radiotherapy protectants.

One 5-ARI, finasteride, is marketed currently for male-pattern baldness, benign prostatic hyperplasia (BPH), and lower urinary tract [obstructive] symptoms (LUTS). The second, dutasteride, is currently in clinical trials.

Based on the observation that this already-available drug inhibited the enzyme known to drive prostate cancer, investigators conducted the Prostate Cancer Prevention Trial (PCPT), which specifically investigated chemoprevention of prostate cancer. It is the largest and most relevant randomized controlled trial and therefore, the primary source of evidence for this guideline.

The guideline primarily recommends that “asymptomatic men with a PSA =3.0 who are regularly screened with PSA or are anticipating undergoing annual PSA screening for early detection of prostate cancer may benefit from a discussion of both the benefits of 5-ARIs for seven years for the prevention of prostate cancer and the potential risks (including the possibility of high-grade prostate cancer).”

The ASCO/AUA guideline reviews the evidence regarding the risks and benefits of a 5-ARI for men age 50 or older who receive regular screening and with PSAs less than or equal to 3 ng/mL who take finasteride for seven years. In the PCPT, finasteride both decreased the cumulative incidence of prostate cancer and increased the incidence of high-grade cancer. These contradictory findings led 12 of 13 Guideline Expert Panel members to conclude that though the latter finding could not be ruled out with certainty, it was most likely a research artifact. Recent publications made headlines by providing evidence that further supported this conclusion.¹

The guideline discusses potential risks of finasteride, including sexual side effects (which may decrease over time). Other potential benefits of the drug include a decrease in lower urinary tract symptoms and a decreased risk of surgery to treat these symptoms.

The guideline recommends that clinicians discuss these findings and the facts that are known and unknown about finasteride for chemoprevention. According to Expert Panel co-Chair, Barnett S. Kramer, MD, MPH, of the National Institutes of Health (NIH), “the ultimate decision is up to the man.” Currently, the effect of long-term finasteride use on mortality is unknown, as is the effect among men who do not receive regular screening. The guideline also recommends discussion with men who are taking finasteride for benign conditions and includes a section on “Doctor-Patient Communication.” A Discussion Guide provided with the guideline is “an additional aid for the man to make the decision,” Dr. Kramer, Editor in Chief of the Journal of the National Cancer Institute (JNCI), said.

The guideline states that clinicians should inform men that finasteride does not eliminate the risk of prostate cancer and help them understand the potential implications of the high-grade finding, along with the potential side effects and benefits of the drug. Physicians should also communicate that the effects of a finasteride regimen that lasts longer than seven years and the drug’s implications for mortality are unknown.

Though the study looked for disparities based on race, ethnicity, age, and family history, researchers found no such differences, particularly by ethnicity or race. 92% of the men in the primary clinical trial were white, which limited this analysis.

The Discussion Guide, the full text of the guideline, a guideline summary, and a slide set, are available at www.asco.org/guidelines/5ari.




Reference
¹. Kolata G. “New Take on a Prostate Drug, and a New Debate.”  New York Times.  June 15, 2008.