October 2, 2003

A great deal of interesting and exciting news concerning a study about prostate cancer prevention has recently been made public. Results from the Prostate Cancer Prevention Trial (PCPT) are very promising and received significant media coverage around the country; however, the reporting of the trial may have caused some confusion about the findings, and their impact. The following is a summary that may clarify the significance of this very interesting and important study about prostate cancer prevention.

Results from the PCPT, which was funded by the National Cancer Institute (NCI) and coordinated by U.S. researchers with the Southwestern Oncology Group (SWOG), were published in the New England Journal of Medicine on July 17, 2003. The main objective of the study was to determine whether the administration of finasteride 5 mg (PROSCAR), compared to placebo, could reduce the prevalence of prostate cancer over a seven-year period. As the primary objective of the trial was achieved before its completion, an independent committee that oversaw the study decided to reveal the results.

A total of 18,882 men 55 years of age or older were randomly assigned to the PCPT. Healthy men with no history of prostate cancer and no evidence of prostate disease were recruited into the study. The key findings of the trial show:

• An overall 25 per cent relative risk reduction in prostate cancer, which is highly statistically significant.
• That the reduced prevalence of prostate cancer in men taking finasteride 5 mg was similar regardless of age, race, family history for prostate cancer or prostate specific antigen (PSA) test.
• At the end of seven years, prostate cancer was detected in 803 of the 4368 men in the finasteride group (18.4 per cent) and 1147 of the 4692 men in the placebo group (24.4 per cent).
• Of the 18.4 per cent of men taking finasteride 5 mg who actually did develop prostate cancer, 98 per cent of the cases were considered to be of a "low-grade" cancer category.

The study detected a greater number of tumors of Gleason grade 7, 8, 9 or 10 in the finasteride group (280 of 757 tumors [37.0 per cent], or 6.4 per cent of the 4368 men included in the final analysis) than in the placebo group (237 of 1068 tumors [22.2 per cent], or 5.1 per cent of the 4692 men included in the final analysis).

SWOG study investigators are exploring several hypotheses to explain this finding, such as:

• Finasteride may alter the appearance of the tumor, which in turn may have lead to a tumor grading bias as the pathologist was blinded in this trial.
• Finasteride may create an environment in the prostate that favours the growth of high-grade tumors.
• High-grade tumors tend not to require androgen to grow, so if a tumor is no longer responsive to androgen, it is very unlikely that finasteride will have any effect on them.
• A reduction in prostate volume, as in the case of finasteride treated patients, could increase the likelihood of finding high-grade disease, as the ratio of the tumor size to prostate gland size increases.

Finasteride 5 mg, a specific type-II 5a-reductase inhibitor, was evaluated in the study because it blocks the enzyme in the prostate that is primarily responsible for the production of a hormone that is important for prostate growth. Studies have shown that finasteride 5 mg causes regression of the enlarged prostate, improves urinary flow and improves the symptoms associated with benign prostatic hyperplasia (BPH) a non-cancerous condition where an enlarged prostate gland often causes bothersome symptoms for patients that can impact quality of life.

We have been prescribing finasteride 5 mg for over ten years for the treatment and control of BPH, and it has proven to be a safe and effective treatment. The results of PCPT show that there may be an even more important role for the medication in the future - the prevention of prostate cancer in the appropriate patients. Currently, though, finasteride 5 mg is only indicated for the treatment of BPH, for which it has proven to be highly beneficial either alone or in combination with an alpha-blocker. Patients on finasteride 5 mg have been shown to require less surgery and have less incidence of acute urinary retention (sudden inability to pass urine) in several studies, when followed for four to five years. The potential for finasteride 5 mg to prevent prostate cancer, especially in patients with bothersome symptoms due to BPH and a large prostate, means that these patients may now receive a 2 for 1 benefit that being an improvement in their BPH condition and possibly prevention of their risk of developing prostate cancer. The results of the PCPT are very exciting and we should be open to offering our patients as much information as possible since, for some, this treatment might be beneficial for prostate cancer prevention with or without concomitant BPH. We should all also look forward to further analysis of PCPT, as well as additional research into prostate cancer prevention.

John Trachtenberg, MD, FRSC ©
Professor of Surgery and Director of The Prostate Centre
Princess Margaret Hospital, Toronto

THE PROSTATE CANCER PREVENTION TRIAL The Prostate Cancer Prevention Trial was a double blind, placebo-controlled Phase III safety and efficacy study with finasteride 5 mg and placebo. The study evaluated the difference in prevalence rates of prostate cancer between a group of participants being treated with finasteride 5 mg and a group being treated with placebo over a seven-year period. It was designed to detect reduction in prostate cancer prevalence after seven years between the treatment groups based on prostate biopsy results. ABOUT PROSTATE CANCER At least one in every eight Canadian men over the age of 70 is expected to develop prostate cancer in their lifetime. It is the most common cancer in men, and the second most deadly form of cancer among males after lung cancer. According to the Canadian Cancer Society, an estimated 18,800 Canadian men are diagnosed each year and numbers are expected to increase as men of the baby boomer generation enter their prostate cancer risk years. Certain factors can increase the risk of prostate cancer including age, race, family history, and high testosterone levels.