Sunday, September 24, 2023
This activity is intended for cardiologists, family medicine and primary care clinicians, nurses, pharmacists, hematologists/oncologists, physician assistants, internists, urologists, and other members of the health care team who treat and manage patients receiving androgen deprivation therapy who may be at increased cardiovascular risk.
The goal of this activity is for learners to be better able to describe the association between androgen deprivation therapy for nonmetastatic prostate cancer and subsequent myocardial infarction, stroke, other cardiovascular disease, and all-cause mortality, based on a Norwegian nationwide, longitudinal study.
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CME / ABIM MOC / CE Released: 7/15/2022
Valid for credit through: 7/15/2023, 11:59 PM EST
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Androgen deprivation therapy (ADT) has been a mainstay of prostate cancer treatment for decades, aiming to deprive androgen-dependent prostate cancer cells of circulating androgen and its precursors. ADT is currently recommended as monotherapy or combined with other therapeutics for aggressive and more advanced cancers. It has shown to be greatly beneficial at reducing cancer-related death, but also to cause significant adverse effects.
Patients with prostate cancer have increased cardiovascular disease (CVD) risk and are more likely to die from non-prostate-cancer-specific causes, mainly cardiovascular related, than from prostate cancer. Evidence suggests that ADT may increase risk for cardiovascular morbidity and mortality, and of all-cause mortality, but findings have been contradictory.
ADT for localized prostate cancer increases the risk for myocardial infarction (MI), stroke, and other 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, "[ healthcare team members 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.
Although some previous research has suggested that ADT can increase the risk for 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, Dr 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 up 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 for 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 (HR, 1.29) CVD risk. 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 for 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 for 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.[1]
