Dr. Pedro Barata is an Assistant Professor of Medicine at the Tulane Cancer Center. He’s keenly interested in genitourinary tumors with a particular focus on clinical trials.
Prostatepedia spoke with him recently about the intersection between cardiovascular disease and prostate cancer.
Why do we even talk about cardiovascular disease when it comes to prostate cancer? It doesn’t come up with lung cancer, so why does it in prostate?
Dr. Pedro Barata: When we think about cardiovascular events, it’s actually a growing topic in this field. As treatments get better and better, patients live longer. Some develop cardiovascular events because they just live long enough to experience those long-term toxicities.
In regard to prostate cancer, it’s usually in relation with hormonal therapy. For context, prostate cancer is a hormonally driven disease, and so its tumor growth depends on androgens. We’ve been using surgical castration or androgen deprivation therapy (ADT) to treat men with prostate cancer for several decades. We have been doing this to treat prostate cancer since the guys who discovered this got a Nobel Prize for it in the 60s. There’s a clearer connection between cardiovascular disease and ADT.
Explanations for this increased risk include metabolic changes, such as hyperglycemia, or dyslipidemia, and factors in relation with arteriosclerosis. This has been an ongoing discussion, to determine why ADT is correlated with increased risk for a cardiovascular event and what we can do to prevent that. We use ADT in localized disease combined with radiation therapy. We use it in the biochemical recurrence space. We use it in the advanced setting. And we also have other therapies called novel androgen inhibitors, such as abiraterone or enzalutamide, to explore this pathway. All of these hormonal manipulations give an increased risk for cardiovascular events.
On the other hand, there’s radiation, which is not a strong risk factor in prostate. In the majority of the cases, we end up not irradiating the chest, and so you don’t have an increased risk for cardiovascular events as compared with lung cancer or breast cancer where radiation is given to the chest, especially to the left side where the heart is. So, the risk for cardiovascular disease is mainly in ADT, novel androgen therapies, androgen pathway inhibitors, and chemotherapy to a much lesser extent.
What would you say to a man who’s reading this and doesn’t already have preexisting cardiovascular disease but has been prescribed ADT?
Dr. Barata: The risk is different depending on the patient. It is different when you have someone who already has preexisting cardiovascular risk factors such as high blood pressure or diabetes, for instance. Because we need to use ADT to suppress testosterone levels, the advice is always to go back and control cardiovascular risk factors in the best way possible. That usually includes getting the primary care physician involved in the care. He should have good blood pressure control, good diabetic or glycemic control, and he should focus on diet and exercise. Those are the factors that we can act on, and we can reduce or minimize the increased risks caused by treatment.
So you could address things as they come up?
Dr. Barata: Exactly. In the clinic on a day-to-day basis, apart from talking about prostate cancer, we talk about which risk factors are present, which are not, and what we need to pay attention to. We usually talk about these five things: ADT, diet, bone health, exercise, and good control of cardiovascular factors.
Every time I see a patient who is at moderate or high risk for cardiovascular events, I usually engage a cardiologist with a focus on oncology. They calculate the risk in a more objective manner. When we are concerned about the treatments we’re considering and their cardiovascular risks, involving a cardio-oncologist is a good way of making sure we don’t miss anything.
There are some data, which are not very strong, that suggest that an antagonist has a lower risk compared with an agonist in causing cardiovascular events. This is not settled yet, but there is a large Phase III trial going on to answer the question. Right now, we don’t have a preference. If it turns out that an antagonist correlates with the lower risk for cardiovascular events, then we’ll change our practice, and we’ll start using the antagonist as the treatment of choice.
Do you know who’s running that trial?
Dr. Barata: The trial is called PRONOUNCE. The collaborators of the study are Memorial Sloan Kettering and Duke Institute, and it’s sponsored by a pharma company. It’s still open. It’s a trial comparing the cardiovascular safety of degarelix, which is the LHRH antagonist, versus leuprolide, which is the LHRH agonist, in patients with advanced prostate cancer and cardiovascular disease. (See Prostatepedia February 2019 for a discussion with Dr. Matthew Roe about this trial.)
I predict it might be closed soon because it’s been open to accrual since 2016. We hope to have a result in the next 24 months.
What about after ADT treatment?
Dr. Barata: Fortunately, we cure a lot of patients with prostate cancer. Every time we deliver a treatment that cures but increases the risk for cardiac events, we should let the patient know that their risk doesn’t go away.
Because we deliver hormones for a short period of time for prostate cancer, that’s not as important as it is for other cancers. In testicular cancer, for instance, we follow patients to make sure that we have cardiovascular risk factors under control. So it’s important that survivorship programs for prostate cancer be mindful of cardiovascular events.
Does the impact that ADT has on prostate cancer last even after the ADT has been stopped?
Dr. Barata: We don’t know. In the localized setting, the duration of ADT is relatively short. For instance, if you have intermediate risk prostate cancer, you usually deliver six months of hormones, and if you have a high-risk disease, you treat them for two to three years. We have no long-term data showing the long-term impact on cardiovascular events for patients treated with three years of hormones, where you suppress testosterone for three years. We do know that, if you have advanced prostate cancer, you are usually in a long-term ADT, meaning continuous suppression, and that can last for five or more years. That’s where there’s more data.
If a person has diabetes or a prior history of cardiovascular problems, their primary care physician should be engaged to make sure that, even though we are done with treatments, we are still paying attention to preventable cardiovascular risk factors, like blood pressure, exercise, and diet.
Do you have any advice for men either going into prostate cancer treatment or already undergoing treatment?
Dr. Barata: There’s frequent toxicity in patients diagnosed with GU tumors in general, and prostate cancer is more associated with ADT. Ask your treating physician about your specific risks. What can you do to prevent or minimize cardiovascular events in the future? Is there a role for a cardio-oncologist, a cardiologist with a focus on oncology, on your healthcare team?