Patterns of Declining Use and the Adverse Effect of Primary Androgen Deprivation on All-cause Mortality in Elderly Men with Prostate Cancer

Sammon, Jesse D.; Abdollah, Firas; Reznor, Gally; Pucheril, Daniel; Choueiri, Toni K.; Hu, Jim C.; Kim, Simon P.; Schmid, Marianne; Sood, Akshay; Sun, Maxine; Kibel, Adam S.; Nguyen, Paul L.; Menon, Mani; Trinh, Quoc Dien

doi:10.1016/j.eururo.2014.10.018

Cited by 44 publications

(29 citation statements)

References 30 publications

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“…Indeed, worse overall survival has been show for men with localized PCa treated with primary ADT [30,32,33]. A possible explanation for this finding may be the competing risks of other-cause mortality in these patients [34].…”

Section: Discussionmentioning

confidence: 88%

“…The impact of ADT on cardiac events/mortality was examined within the comorbidity-adjusted life expectancy subgroups according to Cho et al [29] to account for the influence of coexisting comorbidities [30]. Briefly, the effect of individual comorbidities on survival was estimated with Cox proportional hazards modelling, and the weights for the individual comorbid conditions comprised the coefficient estimates of the condition indicators.…”

Section: Endpointsmentioning

confidence: 99%

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

et al. 2015

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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.

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Section: Discussionmentioning

confidence: 88%

Section: Endpointsmentioning

confidence: 99%

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

et al. 2015

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“…In this context, studies based on several of these data sources have demonstrated that better outcomes might be achieved in high-volume hospitals and/or with more experienced surgeons [21,76]. The evaluation of large cohorts with follow-up data on cancer control has an important role in assessment of the safety and efficacy of PCa treatments [77][78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][93][94]. Data on health-related quality of life after treatment can also be analyzed.…”

Section: 4mentioning

confidence: 99%

Prostate Cancer Registries: Current Status and Future Directions

Gandaglia¹,

Bray

Cooperberg

et al. 2016

European Urology

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Context: Disease-specific registries that enroll a considerable number of patients play a major role in prostate cancer (PCa) research. Objective: To evaluate available registries, describe their strengths and limitations, and discuss the potential future role of PCa registries in outcomes research. Evidence acquisition: We performed a literature review of the Medline, Embase, and Web of Science databases. The search strategy included the terms prostate cancer, outcomes, statistical approaches, population-based cohorts, registries of outcomes, and epidemiological studies, alone or in combination. We limited our search to studies published between January 2005 and January 2015. Evidence synthesis: Several population-based and prospective disease-specific registries are currently available for prostate cancer. Studies performed using these data sources provide important information on incidence and mortality, disease characteristics at presentation, risk factors, trends in utilization of health care services, disparities in access to treatment, quality of care, long-term oncologic and health-related quality of life outcomes, and costs associated with management of the disease. Although data from these registries have some limitations, statistical methods are available that can address certain biases and increase the internal and external validity of such analyses. In the future, improvements in data quality, collection of tissue samples, and the availability of data feedback to health care providers will increase the relevance of studies built on population-based and disease-specific registries. Conclusions: The strengths and limitations of PCa registries should be carefully considered when planning studies using these databases. Although randomized controlled trials still provide the highest level of evidence, large registries play an important and growing role in advancing PCa research and care. Patient summary: Several population-based and prospective disease-specific registries for prostate cancer are currently available. Analyses of data from these registries yield information that is clinically relevant for the management of patients with prostate cancer.

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“…67 Furthermore, the preponderance of evidence from multiple large population based studies demonstrates no improvement, and in some causes worse survival, with the use of primary ADT. 68–71 As a result, guidelines from both the NCCN and the AUA both recommend against the use of primary androgen deprivation therapy. 72,73 …”

Section: Hormone Therapymentioning

confidence: 99%

The comparative oncologic effectiveness of available management strategies for clinically localized prostate cancer

Tyson

Penson

Resnick

2017

Urologic Oncology: Seminars and Original Investigations

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Patterns of Declining Use and the Adverse Effect of Primary Androgen Deprivation on All-cause Mortality in Elderly Men with Prostate Cancer

Cited by 44 publications

References 30 publications

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

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

Prostate Cancer Registries: Current Status and Future Directions

The comparative oncologic effectiveness of available management strategies for clinically localized prostate cancer

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