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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

      Purpose

      It is unknown whether the excess risk of all-cause mortality (ACM) observed when androgen deprivation therapy (ADT) is added to radiation for men with prostate cancer and a history of congestive heart failure (CHF) or myocardial infarction (MI) also applies to those with high-risk disease.

      Methods and Materials

      Of 14,594 men with cT1c–T3aN0M0 prostate cancer treated with brachytherapy-based radiation from 1991 through 2006, 1,378 (9.4%) with a history of CHF or MI comprised the study cohort. Of these, 22.6% received supplemental external beam radiation, and 42.9% received a median of 4 months of neoadjuvant ADT. Median age was 71.8 years. Median follow-up was 4.3 years. Cox multivariable analysis tested for an association between ADT use and ACM within risk groups, after adjusting for treatment factors, prognostic factors, and propensity score for ADT.

      Results

      ADT was associated with significantly increased ACM (adjusted hazard ratio [AHR] = 1.76; 95% confidence interval [CI], 1.32–2.34; p = 0.0001), with 5-year estimates of 22.71% with ADT and 11.62% without ADT. The impact of ADT on ACM by risk group was as follows: high-risk AHR = 2.57; 95% CI, 1.17–5.67; p = 0.019; intermediate-risk AHR = 1.75; 95% CI, 1.13–2.73; p = 0.012; low-risk AHR = 1.52; 95% CI, 0.96–2.43; p = 0.075).

      Conclusions

      Among patients with a history of CHF or MI treated with brachytherapy-based radiation, ADT was associated with increased all-cause mortality, even for patients with high-risk disease. Although ADT has been shown in Phase III studies to improve overall survival in high-risk disease, the small subgroup of high-risk patients with a history of CHF or MI, who represented about 9% of the patients, may be harmed by ADT.
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      References

        • Bolla M.
        • Gonzalez D.
        • Warde P.
        • et al.
        Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin.
        N Engl J Med. 1997; 337: 295-300
        • D’Amico A.V.
        • Chen M.H.
        • Renshaw A.A.
        • et al.
        Androgen suppression and radiation vs radiation alone for prostate cancer: A randomized trial.
        JAMA. 2008; 299: 289-295
      1. McGowan DG, Jones CU, Hunt D, et al. Short-term endocrine therapy prior to and during radiation therapy improves overall survival in patients with T1b-T2b adenocarcinoma of the prostate and PSA ≤20: Initial Results of RTOG 94-08. American Society for Therapeutic Radiology and Oncology 2009 Annual Meeting Proceedings, 2009.

        • Saylor P.J.
        • Smith M.R.
        Adverse effects of androgen deprivation therapy: Defining the problem and promoting health among men with prostate cancer.
        J Natl Compr Cancer Network. 2010; 8: 211-223
        • Smith M.R.
        • Lee H.
        • Nathan D.M.
        Insulin sensitivity during combined androgen blockade for prostate cancer.
        J Clin Endocrinol Metab. 2006; 91: 1305-1308
        • Keating N.L.
        • O’Malley A.J.
        • Freedland S.J.
        • et al.
        Diabetes and cardiovascular disease during androgen deprivation therapy: Observational study of veterans with prostate cancer.
        J Natl Cancer Inst. 2010; 102: 39-46
        • Keating N.L.
        • O’Malley A.J.
        • Smith M.R.
        Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer.
        J Clin Oncol. 2006; 24: 4448-4456
        • D’Amico A.V.
        • Denham J.W.
        • Crook J.
        • et al.
        Influence of androgen suppression therapy for prostate cancer on the frequency and timing of fatal myocardial infarctions.
        J Clin Oncol. 2007; 25: 2420-2425
        • Nanda A.
        • Chen M.H.
        • Braccioforte M.H.
        • et al.
        Hormonal therapy use for prostate cancer and mortality in men with coronary artery disease-induced congestive heart failure or myocardial infarction.
        JAMA. 2009; 302: 866-873
      2. The NCCN Clinical Practice Guidelines in Oncology PROSTATE CANCER (Version 1.2010).
        National Comprehensive Cancer Network, Fort Washington, PA2010
        • Cox D.R.
        Regression models and life-tables.
        J Royal Stat Soc Ser B Methodol. 1972; 34: 187-220
        • Newgard C.D.
        • Hedges J.R.
        • Arthur M.
        • et al.
        Advanced statistics: The propensity score—a method for estimating treatment effect in observational research.
        Acad Emerg Med. 2004; 11: 953-961
        • Korn E.L.
        • Graubard B.I.
        • Midthune D.
        Time-to-event analysis of longitudinal follow-up of a survey: Choice of the time-scale.
        Am J Epidemiol. 1997; 145: 72-80
        • Kaplan E.L.
        • Meier P.
        Nonparametric estimation from incomplete observations.
        J Am Statist Assoc. 1958; 53: 457-481
        • Mantel N.
        Evaluation of survival data and two new rank order statistics arising in its consideration.
        Cancer Chemother Rep. 1966; 50: 163-170
        • Efstathiou J.A.
        • Bae K.
        • Shipley W.U.
        • et al.
        Cardiovascular mortality after androgen deprivation therapy for locally advanced prostate cancer: RTOG 85-31.
        J Clin Oncol. 2009; 27: 92-99
        • Roach 3rd, M.
        • Bae K.
        • Speight J.
        • et al.
        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: 585-591
        • D’Amico A.V.
        • Chen M.H.
        • Renshaw A.A.
        • et al.
        Causes of death in men undergoing androgen suppression therapy for newly diagnosed localized or recurrent prostate cancer.
        Cancer. 2008; 113: 3290-3297
        • Horwitz E.M.
        • Bae K.
        • Hanks G.E.
        • et al.
        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: 2497-2504
        • Denham J.W.
        • Steigler A.
        • Lamb D.S.
        • et al.
        Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: Results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial.
        Lancet Oncol. 2005; 6: 841-850

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