Look and You Will Find It: Practical Considerations for Improving Multidisciplinary Management of Androgen-Deprivation Therapy–Induced Cardiometabolic Toxicity

Patients with cancer are surviving longer and are at increasingly higher risk for developing cardiovascular disease, which threatens to undermine cancer outcomes by adversely affecting shortand long-term morbidity and mortality. Accordingly, the cardio-oncology field has emerged to address the cardiovascular consequences of cancer and cancer therapies by promoting awareness of cardiovascular risk factors andcareneedsofpatientswithcancer, and by collaboration among oncologists and cardiologists aimed at mitigating cardiovascular morbidity and mortality while avoiding unnecessary discontinuation of essential anticancer therapy or overtreatment of individuals not at risk. Thus far, a major focus in cardio-oncology has been on the myocardial toxicities of conventional and novel anticancer agents associated with an increased risk of cardiomyopathy and symptomatic heart failure. The potential adverse metabolic effects of various cancer therapies and their contribution to cardiovascular injury and disease have received comparatively less attention. In the accompanying clinical review, Gupta et al have addressed the underappreciated cardiometabolic toxicities of androgen-deprivation therapy (ADT), including novel agents, in prostate cancer. Conventional ADT that results in lowering total serum testosterone to less than 50 ng/dL is the mainstay of treatment for advanced prostate cancer with about 600,000 men in the United States currently receiving ADT. However, despite demonstrated efficacy, conventional ADT causes multiple detrimental metabolic and physical adverse effects, including muscle wasting (atrophy), decreased lean body mass (sarcopenia), increased body fatmass (obesity), and increased insulin resistance, which lead to a 44% increased risk of new onset type 2 diabetes and 16% risk of new ischemic heart disease. As Gupta et al describe in their review, novel ADT agents (ie, enzalutamide, abiraterone, and apalutamide) may exacerbate these adverse effects. We believe these cardiometabolic toxicities are actually low-hanging fruit that may be monitored easily by using simple, readily available elements of the history (Do you smoke? Do you exercise?), physical examination (body mass index, bloodpressure), andbloodbiomarkers that areubiquitous andwell-accepted surrogate risk markers for coronary heart disease (lipid profile, fasting glucose, or hemoglobinA1c). By comparison, strategies for