Susan Slovin, MD, PhD: We’re here today to look at cardiovascular disease and how hormone therapy influences that. The question, of course, is, why look at cardiovascular disease? What data would have us concerned? Why would I be asking Dr. Gupta to really weigh in on several of my patients when we start hormonal therapy?
It’s interesting to note that as patients get older, there is a higher risk for cardiovascular disease. It’s a common cause of death in men with prostate cancer. We do know that LHRH agonists such as leuprolide, for example, have been linked to a higher cardiovascular mortality and morbidity. This is based on several papers, many of which have been largely retrospective and have not really been based on randomized clinical trials.
Nevertheless, the data suggest that there is an adverse effect on the cardiovascular system. It starts off very early. We can usually see it within the first year of treatment. Therefore, if a patient comes in with prostate cancer—metastatic, localized, it makes no difference—the fact that preexisting cardiovascular disease is present may put this person at a greater risk for other events. Therefore, it’s extremely important that we coordinate multidisciplinary care in the patient who has this. What’s also very important is recognizing, very early on, that it’s not the oncologist’s job to just monitor blood pressure. We need to get the internist, the primary care physician, and the cardiologist involved, particularly in these patients who are at high risk.
The incidence of cardiovascular disease in men with prostate cancer, as I’ve mentioned before, is high. If you look at the panel on your left, which shows the Y axis and the age-specific incidence per 100,000 people, these are men with prostate cancer. You can see that the peak age for diagnosis is roughly between age 70 and age 79. On the right, you can see the cardiovascular events. If you look at the very light blue, and you look on the X axis— ages 40 to 49, 50 to 59, 60 to 69, and the like—those patients in the light blue represent all patients who have some form of cardiovascular disease. As you can see, certainly, if somebody reaches the 90- to 95-year interval, their risk for cardiovascular disease is substantially higher. But, more importantly, if you look at the darker blue, there is a representation of major cardiovascular events. They’ve been defined as myocardial infarction, stroke, or death due to any form of cardiovascular disease, either alone or following complications of coronary revascularization. The point is, it really goes up significantly over time. So, this is an area where it is extremely important to recognize the potential for adverse events.
As mentioned, it’s the second leading cause of death in men with prostate cancer. As early as probably the early 2000s, 2 studies that looked at the effects of intermittent hormonal therapy discovered something very unusual. Patients had an increased risk for cardiovascular events. On your left, you can see that the EORTC (European Organisation for Research and Treatment of Cancer), based on a trial of intermittent hormonal therapy, found that patients had improved in quality of life and survival with intermittent hormonal therapy as opposed to patients who were on continuous hormonal therapy. As you notice in the pie chart, the risk of cardiovascular disease was as high as 34% in those patients who were on continuous androgen deprivation therapy.
Similarly, the Southern European Urology Group showed something equally of interest—again, intermittent androgen deprivation therapy but with the caveat that they didn’t seem to see a difference between improvement in survival whether you were on continuous androgen deprivation therapy or intermittent androgen deprivation therapy. But again, for those patients who were on continuous therapy, you’ll notice that cardiovascular disease was 27%—higher than would have been anticipated.
Transcript Edited for Clarity