Cardiac Complications and Mortality in Men with Prostate Cancer Treated with Brachytherapy with or without Neoadjuvant Hormonal Therapy

Reviewer: Christine Hill-Kayser, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 9, 2009

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Presenter: A. Nanda
Presenter's Affiliation: Harvard Radiation Oncology Program, Boston, MA
Type of Session: Scientific

Background

  • Multiple studies have demonstrated benefit in biochemical and disease-free survival in men with intermediate and high-risk prostate cancer receiving androgen ablation therapy in combination with radiotherapy (D’Amico, 2004; Denham, 2005).
  • Androgen ablation has been demonstrated to contribute to other health risks, including decreased bone health and increased risk of fracture (Shahinian, 2005), and increased risk of diabetes and coronary heart disease (Keating, 2006).
  • Most recently, benefit of androgen ablation treatment has been demonstrated to be countered by risk of death from competing health risks escalated by this treatment in patients with moderate to severe comorbidities (D’Amico, 2008).
  • Androgen ablation treatment has not been demonstrated definitively to provide benefit in treatment of low-risk prostate cancer, and its implications in this population are thus not well understood.
  • Generally, brachytherapy for prostate cancer is a treatment modality reserved for patients with low-risk disease. In some patients, androgen ablation treatment may be delivered prior to brachytherapy seed placement in order to provide gland downsizing and reduction of pubic arch interference.
  • This study was undertaken to investigate the impact on all-cause mortality of use of neoadjuvant androgen ablation in men undergoing brachytherapy for prostate cancer.

Materials and Methods

  • The study was designed as a retrospective cohort study considering men treated for prostate cancer with brachytherapy at the Chicago Prostate Cancer Center between 1997 and 2006, and for whom at least one year of follow-up was available.
  • 5071 study participants were identified.
    • Median age was 69.5 years (inner quartile range 63-74 years).
    • Median follow-up was 4.8 years
    • All had pathologically diagnosed prostate cancer, T1-3, N0, M0.
    • All were treated definitively with brachytherapy using iodine-125, palladium-103, or cesium-137.
    • 11% underwent supplementary external beam radiotherapy.
    • 30% underwent neoadjuvant total androgen suppression, with a median duration of 4 months (inner quartile range 3-4 months).
  • Men were assessed in three cohorts:
    • Those with no comorbidities
    • Those with one cardiovascular risk factor, including diabetes mellitus, hypertension, or hypercholesterolemia
    • Those with known coronary artery disease resulting in either prior myocardial infarction (MI) or congestive heart failure (CHF).
  • A Cox regression analysis was performed to assess whether addition of total androgen suppression to brachytherapy affected time to all-cause mortality.
    • Age, year of treatment, supplemental external beam radiotherapy use, and known prostate cancer prognostic factors (Gleason score, tumor stage, and PSA level) were adjusted for.

Results

  • Overall, there were 419 deaths within the study population.
  • No significant increased risk of death appeared to be associated with use of androgen suppression when the entire population was examined [11% vs. 7%, hazard ratio (HR) 1.08, p = 0.46].
  • Of the entire cohort considered, 52% of men had no identified comorbidities, 43% had a single comorbidity, and 5% had either prior MI or CHF.
  • All-cause mortality was not affected by the addition of total androgen suppression in men with no comorbidities or one comorbidity.
    • For those without comorbidities, with median follow-up of 5.0 years, incidence of death was 6.7% vs. 9.6% in men receiving androgen ablation treatment versus those not, respectively (HR 0.97, p = 0.86).
    • For those with one comorbidity, with median follow-up of 4.4 years, incidence of death was 10.7% vs. 7% in med receiving androgen ablation versus those not, respectively (HR 1.04, p = 0.82).
  • All-cause mortality was significantly increased in men with either CHF or history of MI receiving androgen ablation as compared to those not, with incidence of death 26.3% vs. 11.2%, respectively (HR 1.96, p = 0.04).

Author's Conclusions

The authors conclude that the use of androgen ablation treatment prior to brachytherapy is associated with an increased risk of all-cause mortality in men with history of MI or CHF, but not in those with no co-morbidity or a single cardiac risk factor.

Clinical/Scientific Implications

  • This study is an important addition to the emerging body of literature demonstrating risk of cardiac and other morbidity associated with use of androgen ablation treatment.
  • It examines this potential risk in a population which has not previously been studied, and may serve to raise awareness of cardiac risks associated with prostate cancer treatment in this population; it does, however, have certain limitations inherent to its design.
    • First, because it is a retrospective study, criteria for diagnosis of comorbidities and details regarding those comorbidities are not available. This type of information, for example, class of heart disease, degree of hypertension, and severity of diabetes, could certainly influence the clinical interpretation of the results presented here.
    • In addition, the authors did not consider patients with more than one cardiac risk factor in this study; this information may be forthcoming.
    • Finally, details of total androgen ablation therapy were not available, and may also be important during clinical decision-making.
  • As a result of these limitations, the study presented here is largely hypothesis generating. It may, however, serve to increase awareness of the potential harm of androgen ablation in men with heart disease, and promote consideration of alternative treatment options. This is particularly important during treatment of men with low-risk disease, for whom many treatment options may exist. For this group, avoidance of use of androgen ablation may be prudent while further information is awaited.


News
Hormones Hike Death Risk in Some Prostate Cancers

Nov 24, 2014 - Men with prostate cancer who receive neoadjuvant hormone therapy in combination with radiotherapy face an increased all-cause mortality risk if they have significant cardiovascular comorbidities, including congestive heart failure or prior myocardial infarction, according to a study reported in the Aug. 26 issue of the Journal of the American Medical Association.



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