Five-alpha-reductase inhibitor drugs, such as finasteride or dutasteride, reduce the risk prostate cancer in men who have routine prostate cancer screening

Wilt TJ, MacDonald R, Hagerty K, Schellhammer P, Kramer BS

Published Online:

April 13, 2011

Five-alpha-reductase inhibitor drugs have potential as chemopreventive agents. Reduction of prostate cancer was similar between racial groups, age groups (aged 65 years or older compared to younger age groups) and those with or without a family history of prostate cancer. Reduction of prostate cancer was limited to men who had a baseline prostate specific antigen (PSA) values less than 4.0 ng/mL. However, use of five-alpha-reductase inhibitors may also increase the risk of high-grade prostate cancer in men undergoing prostate cancer screening. Future research is needed to determine if the use of five-alpha-reductase inhibitors can reduce prostate cancer in men who are not being regularly screened for prostate cancer. Future studies should also determine whether five-alpha-reductase inhibitors can reduce death and prostate cancer death and further evaluate the risk of developing high-grade prostate cancer.

Abstract (click to read)

Background:

Five-alpha-reductase inhibitors (5ARI) are frequently used to treat bothersome lower urinary tract symptoms associated with benign prostatic hyperplasia and male androgenic alopecia. They have potential as chemopreventive agents.

Objectives:

We sought to estimate the effectiveness and harms of 5ARI in preventing prostate cancer.

Search strategy:

MEDLINE, PreMEDLINE, and the Cochrane Collaboration Library were searched through April 2007 to identify randomized trials.

Selection criteria:

For prostate cancer outcomes we included randomized controlled trials of at least 1 year in duration published after 1984. For non-prostate cancer outcomes, randomized trials were included if: they were at least 6 months in duration published after 1999.

Data collection and analysis:

The primary outcome was prostate cancer period-prevalence "for-cause." "For-cause" was defined as prostate cancer clinically detected based on symptoms, an abnormal digital rectal exam, or detected as a result of an abnormal prostate specific antigen value. Trials were categorized as long (> 2 year), mid (1 to 2 years) and short (< 1 year) term.

Main results:

Nine trials reported prostate cancer period-prevalence. Three trials using finasteride lasted four years or longer but only one (the Prostate Cancer Prevention Trial) was specifically designed to assess the impact of 5ARI on prostate cancer period-prevalence. The mean age of enrollees was 64.6 years, 91% were white, mean PSA was 2.1 ng/mL. For-cause prostate cancers comprised 54% of all cancers detected. Finasteride was associated with a 26% relative risk reduction in prostate cancers detected for-cause among all randomized subjects (relative risk 0.74 (95% CI 0.67 to 0.83); absolute risk reduction = 1.4% (3.5% versus 4.9%). Six trials assessed prostate cancers detected overall with a pooled 26% relative reduction favoring 5ARI (relative risk 0.74 (95% CI 0.55 to1.00); 2.9% absolute reduction (6.3% versus 9.2%). Reductions were observed regardless of age, race or family history of prostate cancer but not among men with baseline PSA > 4.0 ng/mL. A greater number of high Gleason score tumors (7 to 10 or 8 to 10) occurred in men on finasteride in the PCPT. Impaired sexual or erectile function or endocrine effects were more common with finasteride than placebo.

Authors' conclusions:

Five-alpha-reductase inhibitors reduce prostate cancer risk but may increase the risk of high-grade disease in men who are undergoing regular screening for prostate cancer using prostate specific antigen and digital rectal examination. Effects are consistent across race, family history and age and possibly 5ARI but were limited to men with baseline PSA values < 4.0 ng/mL. The impact of 5ARI on absolute or relative rates of prostate cancer in men who are not being regularly screened is not clear. Information is inadequate to assess the impact of 5ARI on mortality.

This record should be cited as:

Wilt TJ, MacDonald R, Hagerty K, Schellhammer P, Kramer BS. 5-alpha-reductase inhibitors for prostate cancer prevention. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD007091. DOI: 10.1002/14651858.CD007091

Assessed as up to date:

February 14, 2008

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Primary Review Group:

Prostatic Diseases and Urologic Cancers Group

PEARLS - Practical Evidence About Real Life Situations (click to read)

Clinical question:

How effective are five-alpha-reductase inhibitors (5 ARIs) in preventing prostate cancer?

Bottom line:

5 ARIs reduce the risk of prostate cancer in men who undergo routine prostate cancer screening* using prostate specific antigen (PSA) and digital rectal examination. However, 71 men aged 55 or older would need to be treated (NNT) with a 5 ARI for up to seven years in order to prevent one case of prostate cancer. Effects were consistent across age, family history and ethnicity but were limited to men with baseline PSA values < 4.0 ng/mL. The duration of studies ranged from 0.5 to 7 years, with three trials enrolling 24,969 men lasting 4 years or longer.

Caveat:

5 ARIs appeared to increase the risk of high-grade prostate cancer (Gleason score of 7-10). Impaired sexual or erectile function (NNH* 25) or endocrine effects, such as gynaecomastia (NNH 50) and reduced libido (NNH 33), were more common with finasteride than placebo. Information was inadequate to assess the impact on mortality. The impact of 5 ARIs on absolute or relative rates of prostate cancer in men who are not being regularly screened is not clear. NNH = Number needed to treat to cause harm in on individual.

Context:

Prostate cancer is the second most common cancer in terms of incidence and the third most common in terms of mortality among New Zealand men.1 5 ARIs, such as finasteride and dutasteride, are frequently used to treat lower urinary tract symptoms associated with benign prostatic hypertrophy and androgenic alopecia. They have potential as chemopreventive agents.

Cochrane Systematic Review:

Wilt TJ et al. Five-alpha-reductase inhibitors for prostate cancer prevention. Cochrane Reviews 2008, Issue 2. Art. No.: CD007091. DOI: 10.1002/14651858.CD007091. This review contains 13 trials involving 34,410 participants.

Authored by:

Brian R McAvoy

Cochrane Primary Health Care Field

Health topics:

Urology > Cancer > Bladder

Urology > Cancer > Prostate

Cancer > Prostate

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Five-alpha-reductase inhibitor drugs, such as finasteride or dutasteride, reduce the risk prostate cancer in men who have routine prostate cancer screening

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