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.

Clinical Research

Assessing the relationship between statin use and oncologic outcomes among men electing active surveillance for localized prostate cancer

Abstract

Background

This study aims to assess the effect of statin therapy on outcomes among men managed with active surveillance.

Methods

This is a retrospective cohort study evaluating 635 men managed with active surveillance from 2005 to 2015 at a large, academic medical center. The primary endpoints of analyses are disease reclassification (i.e., change in volume or grade of cancer on subsequent biopsies after diagnosis), progression to definitive therapy with curative intent (i.e., surgery or radiotherapy), and surveillance failure—defined as the development of either biochemical failure after definitive therapy, metastases, or prostate cancer-specific mortality—among statin and non-statin users. Secondary analyses were performed to assess the effect of statin use on outcomes among men who progressed to definitive treatment.

Results

Three hundred fifty-six (56.1%) patients in the cohort were on statin therapy at the initiation of surveillance. The median age was 66.7 and 63.3 years among statin and non-statin users, respectively. On univariate analysis, there were no differences in the rates of disease reclassification, progression to definitive treatment, and surveillance failure between the statin and non-statin users in the cohort (all p > 0.05). There was no difference in the rate of biochemical failure among men who progressed to definitive therapy when stratified by statin use (p = 0.89). Pathologic data were available for 105 men who progressed to radical prostatectomy while on surveillance at our institution. Duration of statin use (months) was inversely correlated with adverse pathology for radical prostatectomy on both univariate (OR: 0.99; 95% CI 0.98, 0.99; p = 0.03) and multivariate analysis (OR: 0.98; 95% CI 0.97, 0.99; p = 0.02).

Conclusion

Statin use was not associated with any clinical benefit with regard to disease reclassification, progression to definitive treatment, or surveillance failure among men selecting active surveillance at our institution. There was a 2% decrease in the odds of adverse pathology for each month of statin use among the men who progressed to radical prostatectomy while on active surveillance, but it is unclear at this time if this association has any durable impact on surveillance outcomes among men with favorable risk prostate cancer.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1
Fig. 2
Fig. 3

References

  1. 1.

    Cooperberg MR, Carroll PR. Trends in management for patients with localized prostate cancer, 1990–2013. JAMA. 2015;314:80–82.

    CAS  Article  Google Scholar 

  2. 2.

    Tosoian JJ, Mamawala M, Epstein JI, Landis P, Wolf S, Trock BJ, et al. Intermediate and longer-term outcomes from a prospective active-surveillance program for favorable-risk prostate cancer. J Clin Oncol. 2015;33:3379–85.

    Article  Google Scholar 

  3. 3.

    Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, et al. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med. 2016;375:1415–24.

    Article  Google Scholar 

  4. 4.

    Nyame YA, Almassi N, Haywood SC, Greene DJ, Ganesan V, Dai C, et al. Intermediate term outcomes in men with very low/low and intermediate/high risk prostate cancer managed by active surveillance. J Urol. 2017. https://doi.org/10.1016/j.juro.2017.03.123.

  5. 5.

    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 Lond Engl. 2012;379:1103–11.

    CAS  Article  Google Scholar 

  6. 6.

    Breau RH, Karnes RJ, Jacobson DJ, McGree ME, Jacobsen SJ, Nehra A, et al. The Association between Statin Use and the diagnosis of prostate cancer in a population-based cohort. J Urol. 2010;184:494–9.

    Article  Google Scholar 

  7. 7.

    Friedman GD, Flick ED, Udaltsova N, Chan J, Quesenberry CP, Habel LA. Screening statins for possible carcinogenic risk: up to 9 years of follow-up of 361,859 recipients. Pharmacoepidemiol Drug Saf. 2008;17:27–36.

    Article  Google Scholar 

  8. 8.

    Allott EH, Howard LE, Cooperberg MR, Kane CJ, Aronson WJ, Terris MK, et al. Postoperative statin use and risk of biochemical recurrence following radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. BJU Int. 2014;114:661–6.

    CAS  Article  Google Scholar 

  9. 9.

    Jayalath VH, Nayan M, Finelli A, Komisarenki M, Timilshina N, Kulkarni GS, et al. Statin use and time to progression in men on active surveillance for prostate cancer. Prostate Cancer Prostatic Dis. 2018;21:509.

    CAS  Article  Google Scholar 

  10. 10.

    Marshall DT, Savage SJ, Garrett-Mayer E, Keane TE, Hollis BW, Horst RL, et al. Vitamin D3 supplementation at 4000 international units per day for one year results in a decrease of positive cores at repeat biopsy in subjects with low-risk prostate cancer under active surveillance. J Clin Endocrinol Metab. 2012;97:2315–24.

    CAS  Article  Google Scholar 

  11. 11.

    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.

    CAS  Article  Google Scholar 

  12. 12.

    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 

  13. 13.

    Rao S, Porter DC, Chen X, Herliczek T, Lowe M, Keyomarsi K. Lovastatin-mediated G1 arrest is through inhibition of the proteasome, independent of hydroxymethyl glutaryl-CoA reductase. Proc Natl Acad Sci USA. 1999;96:7797–802.

    CAS  Article  Google Scholar 

  14. 14.

    Brown M, Hart C, Tawadros T, Ramani V, Sangar V, Lau M, et al. The differential effects of statins on the metastatic behaviour of prostate cancer. Br J Cancer. 2012;106:1689–96.

    CAS  Article  Google Scholar 

  15. 15.

    Nübel T, Dippold W, Kleinert H, Kaina B, Fritz G. Lovastatin inhibits Rho-regulated expression of E-selectin by TNFalpha and attenuates tumor cell adhesion. FASEB J . 2004;18:140–2.

    Article  Google Scholar 

  16. 16.

    Weis M, Heeschen C, Glassford AJ, Cooke JP. Statins have biphasic effects on angiogenesis. Circulation. 2002;105:739–45.

    CAS  Article  Google Scholar 

  17. 17.

    Youssef S, Stüve O, Patarroyo JC, Ruiz PJ, Radosevich JL, Hur EM, et al. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature. 2002;420:78–84.

    CAS  Article  Google Scholar 

  18. 18.

    Yue S, Li J, Lee S-Y, Lee HJ, Shao T, Song B, et al. Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness. Cell Metab. 2014;19:393–406.

    CAS  Article  Google Scholar 

  19. 19.

    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. https://doi.org/10.1155/2015/762178.

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Yaw A. Nyame.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Nyame, Y.A., Wilkins, L., Greene, D.J. et al. Assessing the relationship between statin use and oncologic outcomes among men electing active surveillance for localized prostate cancer. Prostate Cancer Prostatic Dis 22, 617–623 (2019). https://doi.org/10.1038/s41391-019-0147-0

Download citation

Search

Quick links