Study suggests that androgen deprivation therapy (ADT)may increase the incidence of cardiovascular problems. Click here to read abstract and access article. In an editorial in the same issue of the Journal of the National Cancer Institute , Jerome Seidenfeld, David J. Samson, Peter C. Albertsen attempt to put the study into perspective for physicians and patients. They say:

Selecting a primary therapy is not the only choice facing patients with localized prostate cancer. Some patients are offered androgen deprivation therapy (ADT) after prostatectomy or radiation therapy (adjuvant ADT) that can continue for years. Others are offered several months of ADT (neoadjuvant ADT) before definitive primary therapy. Many trials on adjuvant or neoadjuvant ADT for localized or locally advanced prostate cancer fail to report the key outcome of interest, and most do not report outcomes stratified by risk groups. Some reviews address side effects of ADT but focus primarily on morbidity and quality of life. A recently published Cochrane systematic review reported estimates for outcomes of treatment efficacy by primary therapy (prostatectomy or radiation therapy) and by type of hormonal deprivation (adjuvant or neoadjuvant). ADT use for patients with localized prostate cancer has increased substantially over time , and recent evidence suggests that ADT may be associated with increased risk for diabetes and cardiovascular disease. In this issue of the Journal, Tsai et al. use registry data from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database to evaluate effects of ADT on risk for cardiovascular death………..

Because conclusive evidence is not available from randomized studies, should patients and clinicians ignore the possibility that ADT may increase the risk of cardiovascular death when evaluating the advisability of adding adjuvant or neoadjuvant ADT to primary therapy for localized disease? Dismissing this hypothesis seems imprudent. The authors’ recommendation that patients considering adding ADT should undergo careful cardiovascular evaluation makes sense.

Do these results suggest that ADT increases risk of cardiovascular death only among men given prostatectomy but not among men managed with other primary therapies? This possibility seems less likely. A pooled analysis of three trials that randomly assigned patients to radiation therapy, either with or without short-course ADT, showed statistically significantly shorter times to fatal myocardial infarction among men aged 65 years or older treated with ADT and radiation therapy than among those treated only with radiation therapy. As Tsai et al. point out, the CaPSURE sample treated with prostatectomy was nearly twice as large as the sample treated with other primary therapies, which may have limited the statistical power to detect a statistically significant effect of ADT in the nonprostatectomy group. Finally, it seems unlikely that the metabolic impact of ADT occurs only or even more frequently in patients managed with prostatectomy.

Ideally, the hypothesis that ADT increases risk of cardiovascular death should be studied in groups given the same primary therapy and randomly assigned to ADT or to placebo, in separate studies for adjuvant and neoadjuvant ADT. These studies would help elucidate whether the duration of ADT influences its effect on risk of cardiovascular death and would stratify patients to take baseline cardiovascular risk into account. Researchers need to address whether cardiovascular death continues to increase with longer follow-up than a median of 4 years, particularly in patients aged 40–59 years whose cardiovascular risks increase as they age. Researchers must also ask whether ADT increases the risk of death from causes unrelated to either prostate cancer or cardiovascular events. The article by Tsai et al. has raised an interesting hypothesis, but patients and clinicians need better risk estimates for cardiovascular death associated with ADT use that are based on randomized trials rather than retrospective analysis.

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