Overview

Benefits From Finasteride and Dutasteride Chemoprevention
Harms From Finasteride and Dutasteride Chemoprevention
        Finasteride
        Dutasteride
Other Prevention Interventions

Note: Separate PDQ summaries on Prostate Cancer Screening, Prostate Cancer Treatment, and Levels of Evidence for Cancer Screening and Prevention Studies are also available.

Based on solid evidence, chemoprevention with finasteride and dutasteride reduces the incidence of prostate cancer, but the evidence is inadequate to determine whether chemoprevention with finasteride or dutasteride reduces mortality from prostate cancer.

Magnitude of Effect: Absolute reduction in incidence for more than 7 years with finasteride was 6% (24.4% with placebo and 18.4% with finasteride); relative risk reduction (RRR) for incidence was 24.8% (95% confidence interval [CI], 18.6%–30.6%). There was no difference in the number of men dying from prostate cancer in the two groups, though the number of deaths was small.

In the dutasteride trial, using the restricted crude rate absolute risk reduction was 5.1% at 4 years, and RRR was 22.8% (95% CI, 15.2%–29.8%, P < .001). There was no difference in prostate cancer or overall mortality, though the number of deaths was small and none were due to prostate cancer. The reduction in prostate cancer incidence occurred primarily in Gleason 5 to 6 cancers.[1] The reduction in incidence primarily in less aggressive cancers (i.e., Gleason 5–6) and not in more aggressive cancers (i.e., Gleason 7–10) raises the question of whether this reduction in incidence would lead to any reduction in mortality. This question is presently unanswered.

Study Design: Two randomized controlled trials; one for finasteride and one for dutasteride.

Internal Validity: Good for the outcome of incidence, poor for the outcome of mortality.

Consistency: Good.

External Validity: The studies focused on different populations. The finasteride trial enrolled men with a prostate-specific antigen (PSA) more than 3 ng/mL, constituting the majority of U.S. men, but men with a lower risk of cancer. In the dutasteride trial, men were at somewhat higher risk, with a PSA of 2.5 to 10.0 and a prior negative biopsy. As such, results are generalizable primarily to these respective populations.

Men in the finasteride group had statistically significantly more erectile dysfunction, loss of libido, and gynecomastia than men in the placebo group. Men in the finasteride group had a statistically significant incidence of high-grade (Gleason sum 8–10) cancers during the study.[2] Whether this was a histological artifact or not is uncertain.

Magnitude of Effect: Statistically significant increases in the following outcomes were observed in the finasteride group (a greater fraction of men in the finasteride group [36.8%] temporarily discontinued treatment at some time during the study for reasons other than death or a diagnosis of prostate cancer than in the placebo group [28.9%]):

Percentage in finasteride group versus percentage in placebo group:

Reduced volume of ejaculate (60.4% vs. 47.3%).

Erectile dysfunction (67.4% vs. 61.5%).

Loss of libido (65.4% vs. 59.6%).

Gynecomastia (4.5% vs. 2.8%).

Overall, 4.3% of men in the dutasteride group compared with 2% of men in the placebo group discontinued the trial because of drug-related adverse events (P < .001).Men in the dutasteride group had a higher incidence of decreased libido, loss of libido, decreased semen volume, erectile dysfunction and gynecomastia than men in the placebo group.[1]

Magnitude of Effect: Increases in the following outcomes were observed in the dutasteride group:

Percentage in dutasteride group versus percentage in placebo group:

Decreased libido (3.3% vs. 1.6%).

Loss of libido (1.9% vs. 1.3%).

Decreased semen volume (1.4 vs. 0.2%).

Erectile dysfunction (9.0% vs. 5.7%).

Gynecomastia (1.9% vs. 1.0%).

Study Design: Two randomized controlled trials; one for finasteride and one for dutasteride.

Internal Validity: Good: The finasteride trial used two subject-completed sexual functioning instruments administered at enrollment, randomization, 6 months, and annually over the 7-year study. The dutasteride trial administered a sexual functioning instrument after completion of placebo run-in and annually thereafter.

Consistency: Good (evidence other than the randomized controlled trial supports these effects).

External Validity: As above, the studies evaluated two different populations: PSA less than or equal to 3 ng/mL in the finasteride trial and PSA of 2.5 to 10.0 ng/mL with a prior negative biopsy in the REDUCE trial. The results are most generalizable to these two populations.

The Selenium and Vitamin E Cancer Prevention Trial (SELECT [NCT00006392]) was a large randomized placebo-controlled trial of vitamin E and selenium. It showed no reduction in prostate cancer period prevalence, but an increased risk of prostate cancer with vitamin E alone.[3]

Magnitude of Effect: Compared with the placebo group in which 529 men developed prostate cancer, there was a statistically significant increase in prostate cancer in the vitamin E group (620 cases) but not in the selenium plus vitamin E group (555 cases) or in the selenium group (575 cases). The magnitude of increase in prostate cancer risk with vitamin E alone was 17%.

Study Design for Vitamin E and Selenium: Randomized, placebo-controlled trial of selenium (200 µg/d from L-selenomethionine), vitamin E (400 IU/d of all-rac-[alpha]-tocopheryl acetate), or both.

Internal Validity: Good.

Consistency: Good.

External Validity: Good.

References

1. Andriole GL, Bostwick DG, Brawley OW, et al.: Effect of dutasteride on the risk of prostate cancer. N Engl J Med 362 (13): 1192-202, 2010.  [PUBMED Abstract]
   
   
2. Thompson IM, Goodman PJ, Tangen CM, et al.: The influence of finasteride on the development of prostate cancer. N Engl J Med 349 (3): 215-24, 2003.  [PUBMED Abstract]
   
   
3. Klein EA, Thompson IM Jr, Tangen CM, et al.: Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 306 (14): 1549-56, 2011.  [PUBMED Abstract]