5-α-Reductase inhibitors for prostate cancer chemoprevention: An updated Cochrane systematic review

Timothy J Wilt, Roderick MacDonald, Karen Hagerty, Paul Schellhammer, James Tacklind, Mark R. Somerfield, Barnett S. Kramer

Research output: Contribution to journalReview articlepeer-review

38 Scopus citations

Abstract

Objective: To estimate the benefits and harms of 5-α-reductase inhibitors (5-α-RIs) in preventing prostate cancer. Materials and Methods We searched MEDLINE and the Cochrane Collaboration Library through June 2010 to identify randomized trials. We included articles if they examined 5-α-RI vs control, were ≥1 year in duration and provided clinical outcomes. Our primary outcome was prostate cancer period-prevalence for-cause. Results: Eight studies met inclusion criteria but only the Prostate Cancer Prevention Trial and the Reduction by Dutasteride of Prostate Cancer Events were designed to assess the impact of 5-α-RIs on prostate cancer period-prevalence. The mean age of enrolees was 64 years, 92% were White, and mean PSA level was 3.1 ng/mL. For-cause prostate cancers comprised 54% of all cancers detected in placebo-controlled studies. Compared with placebo, 5-α-RI resulted in a 25% relative risk (RR) reduction in prostate cancers detected for-cause [RR 0.75, 95% confidence interval (CI) 0.67-0.83; 1.4% absolute risk reduction (3.5% vs 4.9%)]. One BPH trial reported that the risk of prostate cancers detected for-cause was significantly reduced with dutasteride and combined dutasteride plus tamsulosin compared with tamsulosin monotherapy. Six trials vs placebo assessed prostate cancers detected overall. There was a 26% RR reduction favouring 5-α-RI [RR 0.74, 95% CI 0.55-1.00; 2.9% absolute risk reduction (6.3% vs 9.2%)]. There were reductions across categories of age, race and family history of prostate cancer. One placebo-controlled trial of men that investigators considered at greater risk for prostate cancer (based on age, elevated PSA level and having a previous suspicion of prostate cancer leading to a prostate biopsy) reported that dutasteride did not reduce prostate cancers detected for-cause based on needle-biopsy but did reduce risk of overall incident prostate cancer detected by biopsy by 23%[RR 0.77, 95% CI 0.70-0.85; absolute reduction 16.1% vs 20.8%]. There were reductions across age, family history of prostate cancer, PSA level, and prostate volume subgroups. Incidences of erectile dysfunction, ejaculate volume, decreased libido, and gynaecomastia were greater with 5-α-RI vs placebo. Conclusion S 5-α-RIs reduce the risk of being diagnosed with prostate cancer among men who are screened regularly for prostate cancer. Information is inadequate to assess the effect of 5-α-RIs on prostate cancer or all-cause mortality. 5-α-RIs increase sexual and erectile dysfunction.

Original languageEnglish (US)
Pages (from-to)1444-1451
Number of pages8
JournalBJU International
Volume106
Issue number10
DOIs
StatePublished - Nov 2010

Keywords

  • 5-α-reductase inhibitor
  • prevention
  • prostate cancer
  • systematic review

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