Headline Facts and Figures
The Influence of Finasteride 5 mg (Proscar®) on the Development of Prostate Cancer:
What Does This New England Journal of Medicine Paper Mean for Users of Finesteride 1 mg (Propecia®)?
The Prostate Cancer Prevention Trial reported in the July 17, 2003, issue of The New England Journal of Medicine studied the effect of finasteride 5 mg (Proscar®) on the development of prostate cancer:
over a 7-year period, in a randomized, placebo-controlled trial ending in February, 2003, in 18,882 men aged 55 or older, with normal prostates and PSA values were given finasteride to determine if a drug prescribed to millions of men to treat prostate gland enlargement can prevent or delay the appearance of prostate cancer in a population most susceptible to development of prostate cancer.
Headline results of the study:
Overall prevalence of prostate cancer in finasteride-treated men was reduced by 24.8% from the prevalence normally expected in men of this age and medical condition, indicating that finasteride 5mg (Proscar®) is effective in preventing or delaying the appearance of prostate cancer.
In men who developed prostate cancer during the study, finasteride 5 mg was associated with a small increased risk for developing a high-malignancy cancer. The reason for this small increased risk is not understood.
Meaning of the study for users of finasteride 1 mg (Propecia®):
Results of the study cannot be generalized from finasteride 5 g (Proscar®) used to treat prostate enlargement to the lower-dose finasteride 1 mg (Propecia®) used to treat hair loss due to androgenetic alopecia. Safety tests of Propecia® have been accepted by the Food and Drug Administration as an indication of safety for use in treating hair loss.
Introduction and Background
On July 17, 2003, the prestigious New England Journal of Medicine published “The Influence of Finasteride on the Development of Prostate Cancer”, a paper reporting the results of a seven-year, multi-center clinical trial. The purpose of the trial was to test the hypothesis that Proscar®, a 5 milligram formulation of finasteride used to treat enlargement of the prostate gland, might reduce risk for prostate cancer—a major cancer risk for men, especially for men of older age.
The “good news and bad news” findings of the study were widely reported in the media, and frequently misreported or misinterpreted. While the study was conducted with the 5 milligram formulation of finasteride (Proscar®), and was concerned only with prostate cancer prevention, the study results raised questions among patients as well as professionals regarding the use of finasteride 1 mg (Propecia®) for treatment of hair loss. The ISHRS believes that questions about the study results in relation to use of finasteride 1 mg (Propecia®) should be asked, but that questions as well as answers should be based upon (1) the facts as reported by the investigators, and (2) interpretation of the study results as reported by the investigators.
Why the Study Was Conducted
The androgenic (male) hormone testosterone and its more potent metabolite dihydrotestosterone are known to influence abnormal growth of tissue in the prostate gland. When abnormal growth is benign, the result is prostate enlargement (hypertrophy) and associated symptoms such as urinary retention. When the abnormal growth is malignant, the result is prostate cancer.
The drug finasteride inhibits the enzyme that converts testosterone into dihydrotestosterone . This reduces the amount of dihydrotestosterone in the body and the amount available to act on prostate tissue. In a 5 milligram formulation, finasteride (Proscar®) is prescribed to treat benign prostate enlargement.
The investigators designed the study to find out – would finasteride 5 mg (Proscar®), shown to be effective in treating benign prostate enlargement, also be effective in preventing or delaying the appearance of malignant growth of prostate tissue (prostate cancer)?
Androgenic hormones have many effects on many different tissues and organs, among them the hair follicle. Dihydrotestosterone has a potent role in causing hair loss due to androgenetic alopecia (See About hair loss for more information). Finasteride in a 1 milligram formulation (Propecia®) is prescribed as a treatment for hair loss. See Nonsurgical hair loss treatment options for more information.
Proscar® and Propecia®: Same Drug, Different Uses
It is important to note that only the effect of finasteride 5 mg (Proscar®) was studied. Proscar® is widely prescribed for its approved use in treating benign prostate enlargement. Lower-dose finasteride 1 mg (Propecia®), widely prescribed to treat hair loss due to androgenetic alopecia, was not used and was not discussed by the investigators. Some newspaper, TV and Web stories have not made the distinction, contributing to confusion about the study results.
The Study Protocol: Who Was Studied for How Long
The Prostate Cancer Prevention Trial was a prospective, randomized, placebo-controlled study—the “gold standard” for obtaining objective results. The study was carried out at 10 medical centers over a seven-year period ending in February, 2003.
Randomized into the study were 18,882 men, age 55 or older, who had normal prostates on physical examination and prostate-specific antigen (PSA) levels of 3.0 ng/ml or lower, indicating no benign or malignant enlargement. Half of the men received finasteride 5 mg (Proscar®) every day, and half received non-active placebo every day over the seven years of the study. Medical and laboratory examinations were performed at regular intervals, and prostate biopsy performed as indicated by results of these examinations. All men were also offered a prostate biopsy at the end of the study. The investigators assumed that 60% of the men either would have an interim diagnosis of prostate cancer during the study, or would have an end-of-study biopsy to detect or rule out the presence of cancer.
Results of the Study
The study was ended in February, 2003, 15 months early, when investigators found that all study objectives had been met.
At the end of the study, 9,060 men were available for final analysis: 4,368 who had received finasteride, and 4,692 who had received placebo. The final analysis showed:
|Finasteride Group||Placebo Group|
|4,368 Men in Final Analysis*||4,692 Men in Final Analysis**|
|Number with Prostate Cancers:803 (18.4%)||Number with Prostate Cancers:1,147 (24.4%)|
|Prostate Cancers Graded More Malignant:
6.4% of 4,368 Men in Final Analysis
(37% of 757 Cancers Graded)
|Prostate Cancers Graded More Malignant:5.1% of 4,692 Men in Final Analysis
(22.2% of 1,068 Cancers Graded)
|Medical Events and Side Effects:
Sexual Dysfunction More Common Than in the Placebo Group
|Medical Events and Side Effects:
Urinary Tract Symptoms More Common Than in the Finasteride Group
|Deaths in Study Group:
5 Over 7 Years
|Deaths in Study Group:
5 Over 7 Years
* See full NEJM paper for all details
** See full NEJM paper for all details
What the Results Mean
Reduction of Prostate Cancer Prevalence
The lifetime risk of prostate cancer in the U.S. is 16.7%. At the end of the study, in the finasteride group prevalence had been reduced 24.8%–a finding that investigators interpreted as showing that finasteride 5 mg (Proscar®) may prevent or delay the appearance of prostate cancer in men aged 55 or older who had no cancer symptoms before initiating the drug. The investigators said that this finding had an overall beneficial effect.
The Enigma of Malignancy
Of the 4,368 men who received finasteride, 6.4% had diagnosed prostate cancer of higher malignancy by the end of the study. Of the 4,692 men who received placebo, 5.1% had diagnosed prostate cancer of higher malignancy by the end of the study. The reason for this small 1.3% difference is unexplained by the study results, but a number of possible explanations were suggested by the investigators: (1) androgen deprivation therapy (therapy that lowers the level of androgen available to tissues and organs) can cause tissue changes that mimic high-grade malignancy when no malignancy is really present; (2) finasteride 5 mg may induce high-malignancy prostate cancers by its actions within prostate tissue cells; or, (3) finasteride 5 mg selects for high-malignancy cancers by selectively inhibiting low-malignancy cancers.
The bottom line, however, is that this study result remains unexplained, and more research is needed.
Advice for Patients Who Use or May Use Finasteride
Finasteride 1 mg (Propecia®)
None of the study results can be generalized to include finasteride 1 mg (Propecia®), the formulation prescribed to treat hair loss. Only higher-dose finasteride 5 mg (Proscar®) was used in the study. The 5 milligram dose is known to be effective in treating prostate enlargement, and the 5 milligram formulation was selected for the study because of its known effect on prostate tissue. Safety studies of finasteride have not revealed any significant side effects to limit use of the 1 milligram formulation (Propecia®) in treatment of hair loss. (See Nonsurgical hair loss treatment options for more discussion of the safety and effectiveness of Propecia®). Patients with questions about the use of Propecia® should discuss them with their physician hair restoration specialists.
Finasteride 5 mg (Proscar®)
Although the investigators studied the effect of finasteride 5 mg on the development of prostate cancer, the drug is not generally prescribed for this purpose. Finasteride 5 mg (Proscar®) is approved for treatment of prostate gland hypertrophy and associated symptoms, and most men who are using the drug are using it for that purpose. The study showed that Proscar® may have an additional benefit in preventing or delaying the appearance of prostate cancer, but also may be associated with a small absolute increase in risk for developing high-malignancy prostate cancer. The reason for the small increase in risk for high-malignancy cancer is not explained by the study results. The investigators recommend:
“Using published information on the outcomes of prostate cancer treatment, men [in consultation with their physicians] can weigh these trade-offs in the context of their own priorities regarding avoidance of prostate cancer as well as their urinary and sexual function to reach a personal decision regarding finasteride use.” [From NEJM paper—see References].
Thompson IM, Goodman PJ, Tangen CM et al. The influence of finasteride on the development of prostate cancer. N Engl J Med 2003; 349:215-224.
Scardino PT. The prevention of prostate cancer—the dilemma [editorial]. N Engl J Med 2003; 349:297-299.
National Cancer Institute. Protocol for Prostate Cancer Prevention Trial.
Brett AS. Commentary. Journal Watch, 7/18/03.