Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Clinical Research
  • Published:

Statin use and time to progression in men on active surveillance for prostate cancer

Prostate Cancer and Prostatic Diseases volume 21, pages 509–515 (2018)Cite this article

Subjects

Abstract

Purpose

Recent evidence suggests that statins may improve prostate cancer outcomes; however, their role in active surveillance (AS) is poorly characterized. We aimed to evaluate the association between statin use at diagnosis and time to progression on AS.

Materials and Methods

Data were obtained from a prospectively maintained cohort of men undergoing AS between 1995 and 2016 at our institution. All men satisfied the low-risk criteria: Gleason score <7, <4 positive cores, <50% involvement of any core, and prostate-specific antigen level <10.0 ng/dL. Kaplan–Meier curves and multivariable Cox proportional hazards were used to assess statin exposure at diagnosis and at time to pathological progression (failing to meet the low-risk criteria at biopsy) and therapeutic progression (first of pathological progression or initiation of definitive therapy). Reclassification at confirmatory biopsy (first postdiagnostic biopsy) and progression beyond confirmatory biopsy were evaluated independently.

Results

Low-risk criteria were met by 797 men. Reclassification at the confirmatory biopsy occurred in 194 (24%) men, 51 (26%) of whom were statin users. Statin use was not associated with reclassification at confirmatory biopsy (odds ratio (OR): 1.24, 95% confidence interval (CI): 0.77–1.99). Among the remaining 603 men (median age: 63 years; follow-up: 60 months; 23% statin users), 149 (24%) had pathologic progression, while 200 (33%) had therapeutic progression. Statin exposure was not associated with pathological (multivariable hazard ratio (HR) 0.79, 95% CI: 0.51–1.23) or therapeutic (multivariable-HR 0.81, 95% CI: 0.55–1.19) progression beyond the confirmatory biopsy. Sensitivity analyses did not alter conclusions.

Conclusions

In our study, statin use at diagnosis was not significantly protective against pathological or therapeutic progression in men undergoing AS for localized, low-risk prostate cancer.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1

Similar content being viewed by others

References

  1. Moyer VA, US Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force precommendation statement. Ann Intern Med. 2012;157:120–34.

    Article  Google Scholar 

  2. Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003;349:215–24.

    Article  CAS  Google Scholar 

  3. Andriole GL, Bostwick DG, Brawley OW, Gomella LG, Marberger M, Montorsi F, REDUCE Study Group, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med. 2010;362:1192–202.

    Article  CAS  Google Scholar 

  4. Fleshner NE, Lucia MS, Egerdie B, Aaron L, Eure G, Nandy I, et al. Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial. Lancet. 2012;379:1103–11.

    Article  CAS  Google Scholar 

  5. Alfaqih MA, Allott EH, Hamilton RJ, Freeman MR, Freedland SJ. The current evidence on statin use and prostate cancer prevention: are we there yet? Nat Rev Urol. 2017;14:107–19.

    Article  CAS  Google Scholar 

  6. Hamilton RJ, Goldberg KC, Platz EA, Freedland SJ. The influence of statin medications on prostate-specific antigen levels. J Natl Cancer Inst. 2008;100:1511–8.

    Article  CAS  Google Scholar 

  7. Chang SL, Harshman LC, Presti JC. Impact of common medications on serum total prostate-specific antigen levels: analysis of the National Health and Nutrition Examination Survey. J Clin Oncol. 2010;28:3951–7.

    Article  Google Scholar 

  8. Bansal D, Undela K, D’Cruz S, Schifano F. Statin use and risk of prostate cancer: a meta-analysis of observational studies. PLoS ONE. 2012;7:e46691.

    Article  CAS  Google Scholar 

  9. Tan P, Wei S, Tang Z, Gao L, Zhang C, Nie P, et al. LDL-lowering therapy and the risk of prostate cancer: a meta-analysis of 6 randomized controlled trials and 36 observational studies. Sci Rep. 2016;6:24521.

    Article  CAS  Google Scholar 

  10. Raval AD, Thakker D, Negi H, Vyas A, Salkini MW. Association between statins and clinical outcomes among men with prostate cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2016;19:151–62.

    Article  CAS  Google Scholar 

  11. Babcook MA, Joshi A, Montellano JA, Shankar E, Gupta S. Statin use in prostate cancer: an update. Nutr Metab Insights. 2016;9:43–50.

    Article  CAS  Google Scholar 

  12. Murtola TJ, Peltomaa AI, Talala K, Määttänen L, Taari K, Tammela TLJ, et al. Statin Use and prostate cancer survival in the Finnish Randomized Study of Screening for Prostate Cancer. Eur Urol Focus. 2016. http://linkinghub.elsevier.com/retrieve/pii/S2405456916300529

  13. Harshman LC, Wang X, Nakabayashi M, Xie W, Valenca L, Werner L, et al. Statin use at the time of initiation of androgen deprivation therapy and time to progression in patients with hormone-sensitive prostate cancer. JAMA Oncol. 2015;1:495–504.

    Article  Google Scholar 

  14. Hamilton RJ, Ding K, Crook JM, O’Callaghan CJ, Higano CS, Dearnaley D, et al. The association between statin use and outcomes in patients initiating androgen deprivation therapy. J Clin Oncol. 2015;33:145–145.

    Article  Google Scholar 

  15. Fraser M, Sabelnykova VY, Yamaguchi TN, Heisler LE, Livingstone J, Huang V, et al. Genomic hallmarks of localized, non-indolent prostate cancer. Nature. 2017;541:359–64.

    Article  CAS  Google Scholar 

  16. Boutros PC, Fraser M, Harding NJ, de Borja R, Trudel D, Lalonde E, et al. Spatial genomic heterogeneity within localized, multifocal prostate cancer. Nat Genet. 2015;47:736–45.

    Article  CAS  Google Scholar 

  17. Keskiväli T, Kujala P, Visakorpi T, Tammela TLJ, Murtola TJ. Statin use and risk of disease recurrence and death after radical prostatectomy. Prostate. 2016;76:469–78.

    Article  Google Scholar 

  18. Vainio P, Lehtinen L, Mirtti T, Hilvo M, Seppänen-Laakso T, Virtanen J, et al. Phospholipase PLA2G7, associated with aggressive prostate cancer, promotes prostate cancer cell migration and invasion and is inhibited by statins. Oncotarget. 2011;2:1176–90.

    Article  Google Scholar 

  19. Platz EA, Till C, Goodman PJ, Parnes HL, Figg WD, Albanes D, et al. Men with low serum cholesterol have a lower risk of high-grade prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial. Cancer Epidemiol Biomarkers Prev. 2009;18:2807–13.

    Article  CAS  Google Scholar 

  20. Schnoeller TJ, Jentzmik F, Schrader AJ, Steinestel J, Schnoeller TJ, Jentzmik F, et al. Influence of serum cholesterol level and statin treatment on prostate cancer aggressiveness. Oncotarget. 2017;5. http://www.oncotarget.com/abstract/16943

  21. Bhindi B, Kulkarni GS, Finelli A, Alibhai SMH, Hamilton RJ, Toi A, et al. Obesity is associated with risk of progression for low-risk prostate cancers managed expectantly. Eur Urol. 2014;66:841–8.

    Article  Google Scholar 

  22. Jacobs EJ, Rodriguez C, Bain EB, Wang Y, Thun MJ, Calle EE. Cholesterol-lowering drugs and advanced prostate cancer incidence in a large U.S. Cohort. Cancer Epidemiol Biomarkers Prev. 2007;16:2213–7.

    Article  CAS  Google Scholar 

  23. Agalliu I, Salinas CA, Hansten PD, Ostrander EA, Stanford JL. Statin use and risk of prostate cancer: results from a population-based epidemiologic study. Am J Epidemiol. 2008;168:250–60.

    Article  Google Scholar 

  24. Finelli A, Trottier G, Lawrentschuk N, Sowerby R, Zlotta AR, Radomski L, et al. Impact of 5α-reductase inhibitors on men followed by active surveillance for prostate cancer. Eur Urol. 2011;59:509–14.

    Article  CAS  Google Scholar 

  25. Liu Y, Chen J-Q, Xie L, Wang J, Li T, He Y, et al. Effect of aspirin and other non-steroidal anti-inflammatory drugs on prostate cancer incidence and mortality: a systematic review and meta-analysis. BMC Med. 2014;12:55.

    Article  CAS  Google Scholar 

  26. Agarwal G, Spuches J, Luchey A, Patel T, Pow-Sang J. The effect of NSAID use on disease progression in patients on active surveillance for prostate cancer. J Urol. 2015;193:e756–7.

    Article  Google Scholar 

  27. Olivan M, Rigau M, Colás E, Garcia M, Montes M, Sequeiros T, et al. Simultaneous treatment with statins and aspirin reduces the risk of prostate cancer detection and tumorigenic properties in prostate cancer cell lines. Biomed Res Int. 2015;2015:1–11.

    Article  Google Scholar 

  28. Fleshner N. Combination statin, acetylsalicylic acid and dutasteride use in prostate cancer. https://clinicaltrials.gov/ct2/show/NCT01428869 accessed: 2017 July Year.

  29. Coogan PF, Kelly JP, Strom BL, Rosenberg L. Statin and NSAID use and prostate cancer risk. Pharmacoepidemiol Drug Saf. 2010;19:752–5.

    Article  CAS  Google Scholar 

  30. Flick ED, Habel LA, Chan KA, Van Den Eeden SK, Quinn VP, Haque R, et al. Statin use and risk of prostate cancer in the California Men’s Health Study Cohort. Cancer Epidemiol Biomarkers Prev. 2007;16:2218–25.

    Article  CAS  Google Scholar 

  31. Hamilton R, Vijai J, Gallagher D, Savage C, Bhatia J, Gaudet M, et al. Analysis of statin medication, genetic variation and prostate cancer outcomes. J Urol. 2011;185:e401.

    Article  Google Scholar 

  32. Postmus I, Verschuren JJW, de Craen AJM, Slagboom PE, Westendorp RGJ, Jukema JW, Trompet S. Pharmacogenetics of statins: achievements, whole-genome analyses and future perspectives. Pharmacogenomics. 2012;13:831–40.

    Article  CAS  Google Scholar 

  33. Sun Q, Arnold RS, Sun CQ, Petros JA. A mitochondrial DNA mutation influences the apoptotic effect of statins on prostate cancer. Prostate. 2015;75:1916–25.

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by grants from Prostate Cancer Canada (PCC) and the Canadian Cancer Society Research Institute (CCSRI).

Author information

Authors and Affiliations

  1. Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada

    Viranda H. Jayalath, Madhur Nayan, Antonio Finelli, Maria Komisarenki, Narhari Timilshina, Girish S. Kulkarni, Neil E. Fleshner, Bimal Bhindi & Robert J. Hamilton

  2. Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Viranda H. Jayalath

  3. Department of Urology, Mayo Clinic, Rochester, MN, USA

    Bimal Bhindi

  4. Department of Pathology, University Health Network, University of Toronto, Toronto, ON, Canada

    Andrew Evans

  5. Department of Uro-Oncology, Mount Sinai Hospital, Toronto, ON, Canada

    Alexandre R. Zlotta

Authors
  1. Viranda H. Jayalath
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Madhur Nayan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Antonio Finelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Komisarenki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Narhari Timilshina
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Girish S. Kulkarni
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Neil E. Fleshner
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bimal Bhindi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Andrew Evans
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Alexandre R. Zlotta
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Robert J. Hamilton
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert J. Hamilton.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jayalath, V.H., Nayan, M., Finelli, A. et al. Statin use and time to progression in men on active surveillance for prostate cancer. Prostate Cancer Prostatic Dis 21, 509–515 (2018). https://doi.org/10.1038/s41391-018-0053-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41391-018-0053-x

This article is cited by

Search

Advanced search

Quick links