June 2008     Volume 2    #2


Dr. Goldenberg to speak in Calgary
Intermittent hormone therapy
PCa prevention with finasteride
CPCN executives welcomed in Ottawa


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Prostate cancer prevention with finasteride: New research

A review of data from the 2003 Prostate Cancer Prevention Trial (PCPT) concludes that finasteride, a drug known to reduce a man's risk of developing prostate cancer, is safer than was once supposed. The drug is a 5-alpha-reductase inhibitor, which, by blocking production of the enzyme 5-alpha-reductase, modifies the effects of the male hormone testosterone on the prostate. Finasteride has long been used in the treatment of benign prostatic hyperplasia (BPH) because it can reduce the size of the prostate. (See the section "5-Alpha-Reductase Inhibitors" of CPCN's web page on BPH.)

Finasteride has been a drug of interest to men at risk for prostate cancer since the Prostate Cancer Prevention Trial. That trial, which involved 18,882 men, found that those taking finasteride had an overall 25 per cent relative risk reduction in prostate cancer incidence. (See the CPCN article "New findings show prostate cancer can be prevented.")

On the down side, the trial detected a greater incidence of high-grade, advanced tumours among the men taking finasteride who did happened to develop prostate cancer. So, as often happens in the wake of clinical trials, medical professionals and researchers, while optimistic, urged caution and more study.

In May 2008, researchers reported the results of further study --- a careful and comprehensive re-examination and re-interpretation of data from the 2003 PCPT. Their findings suggest that finasteride not only reduces prostate cancer incidence overall but also does not cause more aggressive tumours among the men who develop the disease in spite of taking the drug. (See the press release about this study from Weill Cornell Medical College.)

The original finding, "that men taking finasteride had fewer prostate cancers overall, but a higher incidence of grades 7, 8, 9, and 10 cancers," was a "methodological artefact," suggests Dr. Steven Kaplan of Weill Cornell Medical College. According to Dr. Laurence Klotz (Sunnybrook Health Sciences Centre, Toronto) and Dr. Fred Saad (Director of Urologic Oncology at the University of Montreal Hospital Centre), various new analyses of the PCPT results strongly suggest that better detection as opposed to an increased prevalence of high-grade tumours resulted from finasteride use and may have skewed the earlier findings of the Prostate Cancer Prevention Trial. (Hear a Journal of the National Cancer Institute podcast on this subject.).

To simplify, finasteride, because it shrinks the prostate, probably makes these aggressive tumours easier to find rather than encouraging their growth. Dr. Kaplan puts it graphically in a CBC interview: "It's easier to find a cherry pit in a cherry than it is in a watermelon. So from the perspective of finding a tumour, it's much easier to find in a smaller prostate."

After the researchers re-examined the data on biopsies taken from men in the PCPT study, they adjusted this data statistically to account for factors such as baseline prostate-specific antigen (PSA) levels and prostate volume. (The thinking was that finasteride may have reduced PSA to a lesser extent in men with high-grade cancer than in men with low-grade cancer, which might also have contributed to detection bias during the trial.) For men taking finasteride versus the placebo, they found
  • a significant reduction in the incidence of prostate cancers;
  • a significant decline in tumours with Gleason scores 5, 6, and 7;
  • and, when they adjusted for prostate volume, no higher incidence of tumours with Gleason scores of 8, 9, and 10.
Other researchers agree that finasteride does not increase the risk of high-grade prostate cancer. A recent article published in the June 2008 issue of Cancer Prevention Research concludes that "the observed, unadjusted higher risk of high-grade disease with finasteride seems to have been due to facilitated diagnosis resulting primarily from increased biopsy sensitivity with finasteride." These researchers go on to recommend that men undergoing prostate cancer screening or those expressing an interest in prostate cancer prevention be made aware of "the opportunity to take finasteride for preventing prostate cancer." (See an abstract of this article.)  

Dr. Fred Saad is already prescribing the drug to his high-risk patients and is considering its use in older men who have less risk.

Nevertheless, finasteride use can cause negative side effects, and, as always in prostate cancer prevention and therapy, one approach is not the answer for every man. It takes a skilled medical team and experts to advise men of the risks and benefits of using any drug.

Some of the potential side effects of finasteride use include
  • decreased sex drive,
  • erectile dysfuntion,
  • decreased ejaculate amount,
  • and breast enlargement.
However, several recent studies suggest that the drug does not impact sexual function in most men. A double blind placebo-controlled study assessing sexual dysfunction in 17,313 men over a 7-year period found that finasteride "increased sexual dysfunction only slightly and its impact diminished over time." (See an abstract of this article from the Journal of the National Cancer Institute.)

As always, further research on 5-alpha-reductase inhibitors is either planned or underway. Dutasteride, another drug in this class, is currently being investigated for its efficacy in reducing the risk of prostate cancer among men at high risk for the disease. The 4-year REDUCE study (Reduction by Dutasteride of Prostate Cancer Events) should have preliminary results sometime next year. And the 3-year REDEEM trial (Reduction by Dutasteride of Clinical Progression Events in Expectant Management) should be completed in 2010. REDEEM will assess the same drug as a treatment to extend the time to progression in men with low-risk localized prostate cancer who would otherwise undergo active surveillance.

Currently, however, finasteride remains the only agent proven to reduce the risk of prostate cancer.

For more information:

"Androgens and prevention of prostate cancer," Current opinion in endocrinology, diabetes, and obesity, June 2008.

"PCPT, MTOPS and the use of 5ARIs: a Canadian consensus regarding implications for clinical practice," Canadian Urological Association Journal, March 2007.

"A review of phase III clinical trials of prostate cancer chemoprevention," Annals of the Royal College of Surgeons of England, April 2007.
 

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