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Androgen deprivation and radiotherapy in patients with prostate cancer and cardiovascular risk factors: clinical controversies

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Abstract

Introduction

Recent reports of an association between androgen deprivation treatment (ADT) and increased risk of cardiovascular (CV) events have generated debate on the use of ADT in patients with prostate cancer (PCa) and CV comorbidities. This study aims to describe the recommendations of radiation oncologists in the most controversial aspects of treating such patients.

Materials and methods

The project involved 61 oncologists and comprised 4 phases: (1) selection of the most controversial aspects in the administration of ADT in patients with a history of CV disease and PCa, (2) selection of the most relevant published evidence, (3) preparation of case reports, (4) critical reading and discussion. Therapeutic procedures were classified as “highly recommendable”, “recommendable in some cases”, or “not recommendable/not applicable”. For each item assessed, the mode of the scores given, and the percentage of experts who selected each score were calculated.

Results

The panel recommended that patients with high/very high-risk PCa and a history of CV disease should receive gonadotropin-releasing hormone agonists (GnRHa). ADT with GnRHa for 24–36 months + radiotherapy (RT) was also considered highly recommendable. In intermediate-risk PCa and a history of CV, ADT with GnRHa for 6–8 months + RT, and not administering ADT were considered highly recommendable.

Conclusions

Studies are necessary to investigate the impact of ADT on CV mortality in patients who benefit most from adjuvant ADT in terms of survival. In the meantime, the experts believe that clinical evidence on the proven therapeutic benefits of ADT should override concerns about potential cardiac toxicity.

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References

  1. Pagliarulo V, Bracarda S, Eisenberger MA, Mottet N, Schröder FH, Sternberg CN, et al. Contemporary role of androgen deprivation therapy for prostate cancer. Eur Urol. 2012;61:11–25.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Bolla M, Van Tienhoven G, Warde P, Dubois JB, Mirimanoff RO, Storme G, et al. External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol. 2010;11:1066–73.

    Article  CAS  PubMed  Google Scholar 

  3. Pilepich MV, Winter K, Lawton CA, Krisch RE, Wolkov HB, Movsas B. Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma long term results of phase III RTOG85-31. Int J Radiat Oncol Biol Phys. 2005;61:1285–90.

    Article  CAS  PubMed  Google Scholar 

  4. Roach M, Bae K, Speight J, Wolkov HB, Rubin P, Lee RJ. Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610. J Clin Oncol. 2008;26:585–91.

    Article  PubMed  Google Scholar 

  5. Denham JW, Steigler A, Lamb DS, Joseph D, Mameghan H, Turner S, et al. Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results from the Trans-Tasman Radiation Oncology Group 96.01 randomized controlled trial. Lancet Oncol. 2005;6:841–50.

    Article  CAS  PubMed  Google Scholar 

  6. Horwitz EM, Bae K, Hanks GE, Porter A, Grignon DJ, Brereton HD. Ten-year follow-up of radiation therapy oncology group protocol 92-02: a phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer. J Clin Oncol. 2008;26:2497–504.

    Article  CAS  PubMed  Google Scholar 

  7. Zapatero A, Guerrero A, Maldonado X, Alvarez A, González Sansegundo, Cabeza MA et al and GICOR (Grupo Investigacion Clinica Oncologia Radioterapica). Phase III trial comparing long-term versus short-term androgen deprivation combined with high-dose radiotherapy for localized prostate cancer: GICOR protocol DART01/05. J Clin Oncol. 2011, ASCO annual meeting proceedings, 29(Suppl.15):abstract 4580.

  8. Taylor LG, Canfield SE, Du XL. Review of major adverse effects of androgen-deprivation therapy in men with prostate cancer. Cancer. 2009;115:2388–99.

    Article  PubMed  Google Scholar 

  9. Smith MR, O’Malley AJ, Keating NL. Gonadotrophin-releasing hormone agonists, diabetes and cardiovascular disease in men with prostate cancer: which metabolic syndrome? BJU Int. 2008;101(11):1335–6.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Keating NL, O’Malley AJ, Freedland SJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy: observational study of veterans with prostate cancer. J Natl Cancer Inst. 2010;102:39–46.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Efstathiou JA, Bae K, Shipley WU, Hanks GE, Pilepich MV, Sandler HM. Cardiovascular mortality after androgen deprivation therapy for locally advanced prostate cancer: RTOG 85-31. J Clin Oncol. 2009;27:92–9.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Kim J, Vaid M, Tyldesley S, Woods R, Pickles T. Population-based study of cardiovascular mortality among patients with prostate cancer treated with radical external beam radiation therapy with and without adjuvant androgen deprivation therapy at the british columbia cancer agency. Int J Rad Oncol Biol Phys. 2011;80(3):742–50.

    Article  Google Scholar 

  13. Saylor PJ, Smith MR. adverse effects of androgen deprivation therapy: defining the problem and promoting health among men with prostate cancer. J Natl Compr Canc Netw. 2010;8(2):211–23.

    PubMed Central  CAS  PubMed  Google Scholar 

  14. Levine GN, D’Amico AV, Berger P, Clark PE, Eckel RH, Keating NL. Androgen-deprivation therapy in prostate cancer and cardiovascular risk: a science advisory from the american heart association, american cancer society, and american urological association endorsed by the american society for radiation oncology. CA Cancer J Clin. 2010;60(3):194–201.

    Article  PubMed Central  PubMed  Google Scholar 

  15. US Food and Drug Administration. FDA drug safety communication: Update to ongoing safety 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. http://www.fda.gov/Drugs/DrugSafety/ucm229986.htm. Accessed 9 June 2014.

  16. Wilcox C, Kautto A, Steigler A, Denham JW. Androgen deprivation therapy for prostate cancer does not increase cardiovascular mortality in the long term. Oncology. 2012;82:56–8.

    Article  CAS  PubMed  Google Scholar 

  17. D’Amico AV, Chen MH, Renshaw AA, Loffredo M, Kantoff PW. Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial. JAMA. 2008;299(3):289–95.

    PubMed  Google Scholar 

  18. Nanda A, Chen MH, Braccioforte MH, Moran BJ, D’Amico AV. Hormonal therapy use for prostate cancer and mortality in men with coronary artery disease-induced congestive heart failure or myocardial infarction. JAMA. 2009;302(8):866–73.

    Article  CAS  PubMed  Google Scholar 

  19. Nguyen PL, Je Y, Schutz FA, Hoffman KE, Hu JC, Parekh A, et al. Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials. JAMA. 2011;306(21):2359–66.

    Article  CAS  PubMed  Google Scholar 

  20. ACR (American College of Radiology) (2013). Evidence table development—therapeutic studies. http://www.acr.org/~/media/ACR/Documents/AppCriteria/ETDevTherapeutic.pdf. Accessed 9 June 2014.

  21. Critical Appraisal Skills Programme (CASPe). Tools for critical analysis of the scientific literature. http://redcaspe.org/drupal/?q=node/29. Accessed 9 June 2014.

  22. Efstathiou JA, Bae K, Shipley WU, Hanks GE, Pilepich MV, Sandler HM. Cardiovascular mortality and duration of androgen deprivation for locally advanced prostate cancer: analysis of RTOG 92-02. Eur Urol. 2008;54:816–24.

    Article  CAS  PubMed  Google Scholar 

  23. Van Poppel H, Tombal B. Cardiovascular risk during hormonal treatment in patients with prostate cancer. Cancer Manag Res. 2011;3:49–55.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Alibhai SM, Duong-Hua M, Sutradhar R, Fleshner NE, Warde P, Cheung AM. Impact of androgen deprivation therapy on cardiovascular disease and diabetes. J Clin Oncol. 2009;27:3452–8.

    Article  PubMed  Google Scholar 

  25. Efstathiou J. Cardiovascular mortality following short-term androgen deprivation in clinically localized prostate cancer: an analysis of RTOG 94-08. Proc ASTRO 53d annual meeting 2011, 81(Suppl 2): abstract 82.

  26. Nguyen PL, Chen MH, Beckman JA, Beard CJ, Martin NE, Choueiri TK. Influence of androgen deprivation therapy on all-cause mortality in men with high-risk prostate cancer and a history of congestive heart failure or myocardial infarction. Int J Radiat Oncol Biol Phys. 2012;82(4):1411–6.

    Article  PubMed  Google Scholar 

  27. Gandaglia G1, Sun M, Popa I, Schiffmann J, Abdollah F, Trinh QD et al. The impact of the androgen deprivation therapy on the risk of coronary heart disease in patients with non-metastatic prostate cancer: a population-based study. BJU Int. 2014. doi:10.1111/bju.12732.

  28. Jespersen CG, Nørgaard M, Borre M. Androgen-deprivation therapy in treatment of prostate cancer and risk of myocardial infarction and stroke: a nationwide Danish population-based cohort study. Eur Urol. 2014;65:704–9.

    Article  CAS  PubMed  Google Scholar 

  29. Nanda A, Chen MH, Moran BJ, Braccioforte MH, Dosoretz D, Salenius S. Neoadjuvant hormonal therapy use and the risk of death in men with prostate cancer treated with brachytherapy who have no or at least a single risk factor for coronary artery disease. Eur Urol. 2014;65(1):177–85.

    Article  CAS  PubMed  Google Scholar 

  30. Albertsen PC, Klotz L, Tombal B, Grady J, Olesen TK, Nilsson J. Cardiovascular morbidity associated with gonadotropin releasing hormone agonists and an antagonis. Eur Urol. 2014;65:565–73.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Ignacio Azinovic Gamo, Maria Ángeles Cabeza Rodríguez, Alfonso Gómez de Iturriaga Piña, Víctor Macías Hernández, José Carlos Martínez Cedrés, Julia Muñoz García, Amalia Palacios Eito, Astellas Pharma and María de Miguel Gallo for Medical Writing and editorial assistance.

Conflict of interest

None.

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Authors and Affiliations

  1. Servicio de Oncología Radioterápica, Instituto de Investigación Sanitaria IIS-IP, Hospital Universitario de la Princesa, Diego de León 62, 28006, Madrid, Spain

    A. Zapatero

  2. Servicio de Oncología Radioterápica, Hospital Universitario Gregorio Marañón, Madrid, Spain

    C. González San Segundo

  3. Oncología Radioterápica, Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, Spain

    A. Boladeras

  4. Servicio de Oncología Radioterápica, Hospital Clínico Universitario Santiago de Compostela, Santiago de Compostela, Spain

    A. Gómez Caamaño

  5. Department of Radiation Oncology-ERESA, Hospital General Universitario, Valencia, Spain

    J. López Torrecilla

  6. Servicio de Oncologia Radioterápica, Hospital Universitario Vall d’Hebron, Barcelona, Spain

    X. Maldonado

Authors
  1. A. Zapatero
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  2. C. González San Segundo
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  3. A. Boladeras
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  6. X. Maldonado
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Correspondence to A. Zapatero.

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Zapatero, A., González San Segundo, C., Boladeras, A. et al. Androgen deprivation and radiotherapy in patients with prostate cancer and cardiovascular risk factors: clinical controversies. Clin Transl Oncol 17, 223–229 (2015). https://doi.org/10.1007/s12094-014-1217-3

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  • DOI: https://doi.org/10.1007/s12094-014-1217-3

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