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Risk of diabetes complications among those with diabetes receiving androgen deprivation therapy for localized prostate cancer

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Abstract

Purpose

Androgen deprivation therapy (ADT), used increasingly in the treatment of localized prostate cancer, is associated with substantial long-term adverse consequences, including incident diabetes. While previous studies have suggested that ADT negatively influences glycemic control in existing diabetes, its association with diabetes complications has not been investigated. In this study, we examined the association between ADT use and diabetes complications in prostate cancer patients.

Methods

A retrospective cohort study was conducted among men with newly diagnosed localized prostate cancer between 1995 and 2008, enrolled in three integrated health care systems. Men had radical prostatectomy or radiotherapy (curative intent therapy), existing type II diabetes mellitus (T2DM), and were followed through December 2010 (n = 5,336). Cox proportional hazards models were used to examine associations between ADT use and diabetes complications (any complication), and individual complications (diabetic neuropathy, diabetic retinopathy, diabetic amputation or diabetic cataract) after prostate cancer diagnosis.

Results

ADT use was associated with an increased risk of any diabetes complication after prostate cancer diagnosis (adjusted hazard ratio, AHR, 1.12, 95% CI 1.03–1.23) as well as an increased risk of each individual complication compared to non-use.

Conclusion

ADT use in men with T2DM, who received curative intent therapy for prostate cancer, was associated with an increased risk of diabetes complications. These findings support those of previous studies, which showed that ADT worsened diabetes control. Additional, larger studies are required to confirm these findings and to potentially inform the development of a risk-benefit assessment for men with existing T2DM, before initiating ADT.

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References

  1. Cooperberg MR, Grossfeld GD, Lubeck DP et al (2003) National practice patterns and time trends in androgen ablation for localized prostate cancer. J Natl Cancer Inst 95(13):981–989

    Article  PubMed  PubMed Central  Google Scholar 

  2. Kawakami J, Cowan JE, Elkin EP et al (2006) Androgen-deprivation therapy as primary treatment for localized prostate cancer: data from Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). Cancer 106(8):1708–1714

    Article  PubMed  Google Scholar 

  3. Keating NL, O’Malley AJ, McNaughton-Collins M et al (2008) Use of androgen deprivation therapy for metastatic prostate cancer in older men. BJU Int 101(9):1077–1083

    Article  PubMed  PubMed Central  Google Scholar 

  4. Zeliadt SB, Etzioni R, Ramsey SD et al (2007) Trends in treatment costs for localized prostate cancer: the healthy screenee effect. Med Care 45(2):154–159

    Article  PubMed  Google Scholar 

  5. Alibhai SM, Duong-Hua M, Sutradhar R et al (2009) Impact of androgen deprivation therapy on cardiovascular disease and diabetes. J Clin Oncol 27(21):3452–3458

    Article  PubMed  PubMed Central  Google Scholar 

  6. Barry MJ, Delorenzo MA, Walker-Corkery ES et al (2006) The rising prevalence of androgen deprivation among older American men since the advent of prostate-specific antigen testing: a population-based cohort study. BJU Int 98(5):973–978

    Article  PubMed  PubMed Central  Google Scholar 

  7. D’Amico AV, Denham JW, Crook J et al (2007) Influence of androgen suppression therapy for prostate cancer on the frequency and timing of fatal myocardial infarctions. J Clin Oncol 25(17):2420–2425

    Article  PubMed  CAS  Google Scholar 

  8. Keating NL, O’Malley AJ, Freedland SJ et al (2010) Diabetes and cardiovascular disease during androgen deprivation therapy: observational study of veterans with prostate cancer. J Natl Cancer Inst 102(1):39–46

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Keating NL, O’Malley AJ, Smith MR (2006) Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol 24(27):4448–4456

    Article  PubMed  CAS  Google Scholar 

  10. Moul JW, Banez LL, Freedland SJ (2007) Rising PSA in nonmetastatic prostate cancer. Oncology 21(12):1436–1445 1454.

    PubMed  Google Scholar 

  11. Shahinian VB, Kuo YF, Freeman JL et al (2005) Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med 352(2):154–164

    Article  PubMed  CAS  Google Scholar 

  12. Wei JT, Gross M, Jaffe CA et al (1999) Androgen deprivation therapy for prostate cancer results in significant loss of bone density. Urology 54(4):607–611

    Article  PubMed  CAS  Google Scholar 

  13. Lu-Yao G, Stukel TA, Yao SL (2004) Changing patterns in competing causes of death in men with prostate cancer: a population based study. J Urol 171(6 Pt 1):2285–2290

    Article  PubMed  Google Scholar 

  14. Smith MR, Lee H, Nathan DM (2006) Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab 91(4):1305–1308

    Article  PubMed  CAS  Google Scholar 

  15. Lage MJ, Barber BL, Markus RA (2007) Association between androgen-deprivation therapy and incidence of diabetes among males with prostate cancer. Urology 70(6):1104–1108

    Article  PubMed  CAS  Google Scholar 

  16. Tsai HK, D’Amico AV, Sadetsky N et al (2007) Androgen deprivation therapy for localized prostate cancer and the risk of cardiovascular mortality. J Natl Cancer Inst 99(20):1516–1524

    Article  PubMed  Google Scholar 

  17. Tsai HT, Keating NL, Van Den Eeden SK et al (2015) Risk of diabetes among patients receiving primary androgen deprivation therapy for clinically localized prostate cancer. J Urol 193(6):1956–1962

    Article  PubMed  CAS  Google Scholar 

  18. US Food and Drug Administration. Review of GnRH agonists and notification to manufacturers of GnRH agonists to add new safety information to labeling regarding increased risk of diabetes and certain cardiovascular diseases, 2011. Available at: http://www.fda.gov/Drugs/DrugSafety/ucm229986.htm

  19. Derweesh IH, Diblasio CJ, Kincade MC et al (2007) Risk of new-onset diabetes mellitus and worsening glycaemic variables for established diabetes in men undergoing androgen-deprivation therapy for prostate cancer. BJU Int 100(5):1060–1065

    PubMed  Google Scholar 

  20. Haidar A, Yassin A, Saad F et al (2007) Effects of androgen deprivation on glycaemic control and on cardiovascular biochemical risk factors in men with advanced prostate cancer with diabetes. Aging Male 10(4):189–196

    Article  PubMed  CAS  Google Scholar 

  21. Keating NL, Liu PH, O’Malley AJ et al (2014) Androgen-deprivation therapy and diabetes control among diabetic men with prostate cancer. Eur Urol 65(4):816–824

    Article  PubMed  CAS  Google Scholar 

  22. Young BA, Lin E, Von Korff M et al (2008) Diabetes complications severity index and risk of mortality, hospitalization, and healthcare utilization. Am J Manag Care 14(1):15–23

    PubMed  PubMed Central  Google Scholar 

  23. Centers for Disease Control. National Diabetes Statistics Report 2014 (2014) Department of Health and Human Services, Atlanta. https://www.cdc.gov/diabetes/pdfs/data/2014-report-estimates-of-diabetes-and-its-burden-in-the-united-states.pdf

  24. Thompson I, Thrasher JB, Aus G et al (2007) Guideline for the management of clinically localized prostate cancer: 2007 update. J Urol 177(6):2106–2131

    Article  PubMed  Google Scholar 

  25. Elixhauser A, Steiner C, Harris DR et al (1998) Comorbidity measures for use with administrative data. Med Care 36(1):8–27

    Article  PubMed  CAS  Google Scholar 

  26. Shahani S, Braga-Basaria M, Basaria S (2008) Androgen deprivation therapy in prostate cancer and metabolic risk for atherosclerosis. J Clin Endocrinol Metab 93(6):2042–2049

    Article  PubMed  CAS  Google Scholar 

  27. Allan CA, Collins VR, Frydenberg M et al (2014) Androgen deprivation therapy complications. Endocr Relat Cancer 21(4):T119-29

    Article  PubMed  CAS  Google Scholar 

  28. King P, Peacock I, Donnelly R (1999) The UK prospective diabetes study (UKPDS): clinical and therapeutic implications for type 2 diabetes. Br J Clin Pharmacol 48(5):643–648

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Huang ES, Laiteerapong N, Liu JY et al (2014) Rates of complications and mortality in older patients with diabetes mellitus: the diabetes and aging study. JAMA Intern Med 174(2):251–258

    Article  PubMed  PubMed Central  Google Scholar 

  30. Cusick M, Meleth AD, Agron E et al (2005) Associations of mortality and diabetes complications in patients with type 1 and type 2 diabetes: early treatment diabetic retinopathy study report no. 27. Diabetes Care 28(3):617–625

    Article  PubMed  Google Scholar 

  31. National Comprehensive Cancer Network. Practice Guidelines in Oncology, v.3.2012, Prostate cancer. http://www.nccn.org/professionals/physician_gls/PDF/prostate.pdf

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Funding

Supported by Grants No. R01CA142934, RC1CA146238 and P30CA051008 from the National Cancer Institute.

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Authors and Affiliations

  1. Clinical and Translational Epidemiology Branch, Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD, USA

    Marie C. Bradley & Andrew N. Freedman

  2. Georgetown University Lombardi Comprehensive Cancer Center, Washington, DC, USA

    Yingjun Zhou & Arnold L. Potosky

  3. Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA

    Marianne Ulcickas Yood

  4. Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA

    Charles P. Quesenbery & Stephen K. Van Den Eeden

  5. Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA

    Reina Haque

  6. Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA

    Andrea E. Cassidy-Bushrow

  7. Kaiser Permanente, Oakland Medical Center, 3600 Broadway, Oakland, CA, USA

    David Aaronson

Authors
  1. Marie C. Bradley
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  2. Yingjun Zhou
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  3. Andrew N. Freedman
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  4. Marianne Ulcickas Yood
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  5. Charles P. Quesenbery
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  6. Reina Haque
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  7. Stephen K. Van Den Eeden
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  8. Andrea E. Cassidy-Bushrow
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  9. David Aaronson
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  10. Arnold L. Potosky
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Corresponding author

Correspondence to Marie C. Bradley.

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Conflict of interest

RH has received research funding from Novartis and AstraZeneca for studies unrelated to the present study. ACB received funding for a study from Novartis, which is unrelated to this study. SV received funding from GlaxoSmithKline for a project unrelated to this study. MB, AP, AF, MUY, XZ, DA, CPQ declare that they have no conflict of interest.

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Bradley, M.C., Zhou, Y., Freedman, A.N. et al. Risk of diabetes complications among those with diabetes receiving androgen deprivation therapy for localized prostate cancer. Cancer Causes Control 29, 785–791 (2018). https://doi.org/10.1007/s10552-018-1050-z

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  • DOI: https://doi.org/10.1007/s10552-018-1050-z

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