AHA issues advisory on potential CV risk of common prostate cancer therapy
: A joint Scientific Advisory from the American Heart Association, American Cancer Society, and American Urological Association advises physicians about the potential risk for cardiovascular disease (CVD) associated with androgen deprivation therapy (ADT), a widely used treatment for prostate cancer.
In the report, co-published by the journals Circulation and CA: A Cancer Journal for Clinicians, a multidisciplinary writing group reviews the potential relationship between ADT and CV events in patients with prostate cancer, and presents suggestions for their evaluation and management.
Glenn Levine (Baylor College of Medicine, Houston, Texas, USA) and co-authors conclude that, despite continuing uncertainty from available data, “it is reasonable… to state that there may be a relationship between ADT and CV events and death.”
They nevertheless recommend that patients in whom ADT is believed to be beneficial do not need to be referred to internists, endocrinologists, or cardiologists for evaluation before initiation of ADT. The decision as to whether or not to initiate ADT in patients with cardiac disease, for whom the benefits should be weighed against the risks, is most appropriately made by the physician treating patient for prostate cancer.
Many internists, cardiologists, and endocrinologists may not be fully aware of the possible effects of ADT on CVD risk yet are likely being consulted in patients initiated ADT because of initial reports of an association between ADT and increased CV events, the writing team explains.
ADT lowers levels of circulating androgens, which promote prostate cancer cell growth, and in combination with external-beam radiation therapy is the standard treatment for high-risk prostate cancer. It is also used is other prostate cancer states where its benefits are less certain.
A substantial amount of data now shows that ADT adversely affects CV risk factors including serum lipoproteins, insulin sensitivity, and obesity. But evidence is lacking for clinical events, with recent studies reporting a relationship between ADT and increased CVD but conflicting data for CV death.
Levine et al note that use of a GnRH (gonadotropin-releasing hormone agonist; a common form of ADT) was associated with a 1.16-fold increased coronary heart disease incidence in one population-based study, and with a 1.20-fold increased risk for serious CV morbidity in another.
Analysis of the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) database revealed a 2.6-fold increased risk for CV death in men with prostate cancer who received some form of ADT prior to radical prostatectomy, and a pooled post-hoc analysis of three randomized trials demonstrated that 6-month adjunctive ADT was associated with a 2-year shorter time to fatal myocardial infarction in men over 65 years undergoing radiation therapy.
However, four other post-hoc analyses of randomized trials found no association between ADT and CV mortality. Notably, the recent European Organization for Research and Treatment of Cancer randomized trial found no difference in fatal cardiac events with 6 months of ADT plus radiotherapy versus 3 years of ADT combined with radiotherapy.
It remains unclear whether the discrepancy relates to study design and limitations, competing prostate cancer mortality risk, or risk primarily confined to those with established coronary artery disease, or indeed a lack of any causal relationship between ADT and CV events, say Levine and co-authors.
They call for future prospective trials assessing CV risk factors before and after ADT and monitoring for adverse CV events.
In the meantime, the team advises that there is presently no reason for specific cardiac testing or coronary intervention in patients with CVD before initiation of ADT.
However, given the metabolic effects of ADT, patients in whom ADT is initiated should be referred to their primary care physician for periodic blood pressure, lipid, and glucose checks, while “prudence and good medical care dictate that patients with cardiac disease receive appropriate secondary preventive measures.”
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By Caroline Price