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  • Review Article
  • Published:

The current evidence on statin use and prostate cancer prevention: are we there yet?

Nature Reviews Urology volume 14, pages 107–119 (2017)Cite this article

Subjects

Key Points

  • Statins are a commonly prescribed class of medications that lower serum cholesterol levels by inhibiting HMG-CoA reductase, the rate-limiting enzyme for cholesterol synthesis in the liver

  • Preclinical research shows that statins can inhibit prostate cancer growth through cholesterol-mediated and non-cholesterol-mediated mechanisms (for example, lipid-raft-mediated and Ras signalling, respectively) that affect pathways essential for cancer formation and progression

  • Of >30 observational studies on statin use and prostate cancer risk published to date, most support the hypothesis that statin use reduces the risk of advanced prostate cancer

  • Increased PSA screening and health-conscious behaviour in statin users might bias some findings but are unlikely to fully explain the inverse association between statin use and prostate cancer risk

  • Statin use also seems to be associated with improved prostate-cancer-specific survival, particularly in men undergoing radiotherapy, suggesting a role for statins in secondary and tertiary prostate cancer prevention

  • Before conducting primary prevention trials, further research into the mechanisms contributing to reported inverse associations is required; however, secondary and tertiary prevention trials in men diagnosed with prostate cancer might soon be performed

Abstract

An increasing amount of data supports an inverse association between statin use and cancer risk. The findings for prostate cancer, particularly advanced disease, are the most promising of all cancers studied. Use of these agents seems to also be associated with improved prostate- cancer-specific survival, particularly in men undergoing radiotherapy, suggesting usefulness of statins in secondary and tertiary prevention. Some study results might be influenced by increased PSA screening and health-conscious behaviour in statin users but these factors are unlikely to completely account for observed beneficial effects. The epidemiological evidence is supported by preclinical studies that show that statins directly inhibit prostate cancer development and progression in cell-based and animal-based models. The antineoplastic effect of statins might arise from a number of cholesterol-mediated and non-cholesterol-mediated mechanisms that affect pathways essential for cancer formation and progression. Understanding these mechanisms is instrumental in drug discovery research for the development of future prostate cancer therapeutics, as well as in designing clinical trials to test a role for statins in prostate cancer prevention. Currently, sufficient data are lacking to support the use of statins for the primary prevention of prostate cancer and further research is clearly warranted. Secondary and tertiary prevention trials in men who have been diagnosed with prostate cancer might soon be performed.

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Figure 1: Statin use, high cholesterol and prostate cancer deaths in the USA.
Figure 2: Mechanisms of prostate cancer growth affected by the mevalonate pathway.
Figure 3: Effects of statin use during the clinical course of prostate cancer.

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Acknowledgements

E.H.A. receives funding support from the American Institute for Cancer Research and S.J.F. receives funding support from the National Institutes of Health Award 1K24CA160653.

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Authors and Affiliations

  1. Division of Urology, Department of Surgery, Duke University School of Medicine, Box 2626, Durham, 27710, North Carolina, USA

    Mahmoud A. Alfaqih

  2. Department of Nutrition, CB 7461, University of North Carolina at Chapel Hill, 135 Dauer Drive, Chapel Hill, 27599, North Carolina, USA

    Emma H. Allott

  3. Division of Urology, Department of Surgical Oncology, University of Toronto, 610 University Avenue, Toronto, M5G 2M9, Ontario, Canada

    Robert J. Hamilton

  4. Division of Cancer Biology and Therapeutics, Departments of Surgery and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, 90048, California, USA

    Michael R. Freeman

  5. Division of Urology, Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8635 West 3rd Street, Suite 1070W, Los Angeles, 90048, California, USA

    Stephen J. Freedland

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  1. Mahmoud A. Alfaqih
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  2. Emma H. Allott
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Contributions

M.A.A. and E.H.A. researched data for the article. E.H.A., R.J.H. and S.J.F. made a substantial contribution to discussion of content. M.A.A., E.H.A. and S.J.F. wrote the article. E.H.A., R.J.H., M.R.F. and S.J.F. reviewed and/or edited the article before submission.

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Correspondence to Stephen J. Freedland.

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The authors declare no competing financial interests.

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Alfaqih, M., Allott, E., Hamilton, R. et al. The current evidence on statin use and prostate cancer prevention: are we there yet?. Nat Rev Urol 14, 107–119 (2017). https://doi.org/10.1038/nrurol.2016.199

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