Dose‐dependent effect of androgen deprivation therapy for localized prostate cancer on adverse cardiac events

Abstract

ObjectivesTo investigate the dose-dependent effect of androgen deprivation therapy (ADT) on adverse cardiac events in elderly men with non-metastatic prostate cancer (PCa) stratified according to life expectancy. Patients and MethodsA total of 50 384 men diagnosed with localized PCa between 1992 and 2007 were identified within the Surveillance, Epidemiology, and End Results registry areas. We compared those who received ADT within 2 years of PCa diagnosis with those who did not, calculated as monthly equivalent doses of GnRH agonists (<8, ≥8 doses), or orchiectomy. Men were further stratified according to life expectancy (<5 years, 5-10 years and >10 years). Adjusted Cox hazard models assessed the risk of new-onset coronary heart disease (CHD), acute myocardial infarction (AMI), sudden cardiac death (SCD) and cardiac-related interventions, as well as any of these events. ResultsOverall, patients receiving GnRH agonists were more likely to experience a cardiac event, with the most pronounced effect among those receiving ≥8 doses (hazard ratio [HR] <8 doses: 1.13, 95% confidence interval [CI] 1.09-1.16, and HR ≥8 doses: 1.18, 95% CI 1.14-1.22; both P < 0.001). The effect of prolonged (≥8 doses) GnRH agonist use on cardiac events was sustained across all strata of life expectancy; however, there was no effect among men with a life expectancy of <5 years and when use of GnRH agonists was limited to <8 doses (HR 0.99, 95% CI 0.67-1.46; P = 0.964). The use of GnRH agonists was associated with a higher risk of CHD (HR <8 doses: 1.13, 95% CI 1.09-1.17 and HR ≥8 doses: 1.17, 95% CI 1.13-1.21; both P < 0.001). Conversely, the use of GnRH was generally not associated with an increased risk of AMI or SCD, except for men who received ≥8 doses of GnRH agonists and had a life expectancy of ≥5 years, who were at a significantly higher risk of SCD (HR for life expectancy 5-10 years: 1.19, 95% CI 1.06-1.33; P = 0.003 and HR for life expectancy >10 years: 1.16, 95% CI 1.04-1.29; P = 0.006). Finally, orchiectomy was not associated with overall cardiac events, AMI or SCD, and was protective with regard to cardiac-related interventions (HR 0.78, 95% CI 0.68-0.90, P = 0.001). ConclusionExposure to ADT with GnRH agonists is associated with an increased risk of cardiac events in elderly men with localized PCa and a decent life expectancy. Clinicians should carefully weigh the risks and benefits of ADT in patients with a prolonged life expectancy. Routine screening and lifestyle interventions are warranted in at-risk subpopulations treated with ADT.

Relationship between androgen deprivation therapy and community‐acquired respiratory infections in patients with prostate cancer

“…A study examining hospitalization patterns for severe infections amongst cancer patients in the year 2001 showed that 51% of the patients were admitted for pneumonia, with PCa accounting for approximately 8% . Furthermore, we found that the risk of experiencing a respiratory event increased with the number of ADT doses received . Our observations serve to validate recently published findings from Chung et al ., who observed an increased risk of pneumonia for PCa patients receiving GnRH agonists .…”

“…Although ADT is an established treatment modality for patients with advanced PCa and recommended as an adjunct to radiotherapy for high‐risk patients, guideline‐discordant use has been reported in men with localized disease, where an oncological benefit has not been shown . Furthermore, there is increasing evidence that ADT in these patients is associated with increased risk of cardiovascular morbidity and mortality, diabetes, acute kidney injury, fractures, and venous thromboembolism …”

Adjuvant androgen deprivation therapy for prostate cancer treated with radiation therapy

“…Men receiving ADT (average duration of 2 years) experienced a 9% absolute increased risk of new incident diabetes, an 11% increased risk of incident coronary heart disease, an approximately 3% increased risk of myocardial infarction and nearly 4% increased risk of sudden cardiac death, findings which were robust to propensity-matched analysis. Surprisingly, these data suggested that even men on short-term duration of ADT (defined as 1–4 months) experienced increased risk of diabetes and heart disease, although other data suggest that the cutpoint of 8 months ADT duration predicts for increased cardiac events ( 53 ). Data from the CaPSURe database ( 54 ) corroborated these findings as well.…”

Variation in National Use of Long-Term ADT by Disease Aggressiveness Among Men With Unfavorable-Risk Prostate Cancer

“…The total corresponding months of androgen suppression were summed as in previous studies. [14][15][16][17] For example, a patient who received 8 injections of leuprolide acetate, 22.5 mg (3-month dosing), would be considered to have completed 2 years of ADT. We also derived the Charlson comorbidity index from Medicare claims data 1 year before prostate cancer diagnosis and categorized the index as 0 to 1 versus 2 or greater using a previously described and validated algorithm.…”