Androgen deprivation therapy (ADT) for localized prostate cancer increases the risk of myocardial infarction (MI), stroke, and other cardiovascular disease (CVD) events as well as death, according to a study from Norway.
These risks appear more pronounced in men with preexisting CVD risk factors and those receiving therapy for longer durations.
Although more data are needed to put these findings in context with respect to overall benefit from ADT, for now, “clinicians should carefully weigh the risks and benefits of ADT when developing a treatment plan, with possible consideration of early intervention for CVD risk factors,” lead author Rachel B. Forster, PhD, and colleagues with the Norwegian Institute of Public Health in Bergen, write.
The study was published online April 30 in the International Journal of Cancer.
While some previous research has suggested that ADT can increase the risk of cardiovascular morbidity and mortality, other studies have not demonstrated such a link, leaving the relationship between prostate cancer treatment and CVD unclear.
To investigate further, Forster and colleagues used Norwegian registry data to identify 30,923 men diagnosed with prostate cancer between 2008 and 2018. Of those patients, 8449 (27%) received primary ADT. Patients were followed for a mean of 2.9 years for CVD events and 3.8 years for mortality.
In the fully adjusted model, ADT was associated with a 13% increased risk of any CVD event, which included MI, stroke, and heart failure (adjusted hazard ratio [HR], 1.13). This association persisted in men at low (HR, 1.17), moderate (HR, 1.11), and high CVD risk (HR, 1.29). ADT was also associated with increased risk for each CVD event individually — MI (HR, 1.18), stroke (HR, 1.21), and heart failure (HR, 1.23).
The risk for all-cause mortality was significantly higher among those who received ADT (HR, 1.49), as well as for each CVD risk group (HR, 1.75 for low, 1.50 for moderate, and 1.17 for high risk). The authors found no association between ADT and atrial fibrillation.
Treatment duration was also a factor in CVD risk. The authors found no association between ADT that was administered for 7 months or less and CVD outcomes. But they did observe associations between treatment for 7 to 18 months and overall CVD outcomes (HR, 1.12) and for stroke (HR, 1.32) and heart failure (HR, 1.25). For ADT lasting more than 18 months, the risk of CVD events overall (HR, 1.23) as well as MI (HR, 1.31) and heart failure (HR, 1.28) were also higher.
Notably, all treatment durations were associated with an increased risk of dying from any cause (HR, 1.52 for ADT for <7 months; HR, 1.35 for ADT for 7 – 18 months; HR, 2.04 for >18 months).
“Although there is evidence of ADT being associated with increased risk of CVD and all-cause mortality, it cannot simply be removed as a treatment option,” the authors write. “Rather, risk reduction and mitigation strategies should be explored, specifically for subgroups of people at moderate risk of CVD.”
For instance, the authors suggest, a patient at higher risk of CVD who requires ADT may benefit from having the duration of treatment reduced. Other mitigation strategies could include careful monitoring and control of modifiable risk factors, such as blood pressure, cholesterol, and diabetes.
“Most importantly, there should be a focus on using clear guidelines to recommend ADT only to patients that have a demonstrated benefit from the treatment,” the authors conclude.
The study had no specific funding. The authors have disclosed no relevant financial relationships.
Int J Cancer. Published online April 30, 2022. Full text
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