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

Authors

Errata

This article is corrected by:

  1. Errata: Corrigendum Volume 107, Issue 2, 344, Article first published online: 5 January 2011

Timothy J. Wilt, Minneapolis VA Center for Chronic Disease Outcomes Research, 1 Veterans Drive (111-0), Minneapolis, MN 55417, USA.e-mail: tim.wilt@va.gov

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.

CONCLUSIONS

  • • 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.

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