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Alicia Morgans: Hi, my name is Alicia Morgans, and I'm a GU Medical Oncologist and Associate Professor of Medicine at Northwestern University. I'm so excited to have here with me today Dr. Vivek Narayan, who is an Assistant Professor of Medicine at the University of Pennsylvania, where he is a GU Medical Oncologist, and really focuses on understanding some of the cardiovascular complications of therapy for patients and wrote a beautiful piece about that. A nice review on GU malignancies and cardiovascular complications. He is here to talk with me about that today. Thank you so much for being here with me, Vivek.

Vivek Narayan: Thanks, Alicia. Happy to be here.

Alicia Morgans: Wonderful. So for this conversation, I'd really like to focus on the cardiovascular complications that are really afflicting men with prostate cancer. These complications are predominantly related to the unique situation that we put them into when we really lower their testosterone with androgen deprivation therapy. And of course, we're doing this in a population that's already vulnerable, an aging male population. So can you tell us a little bit about what they're experiencing?

Vivek Narayan: I think that's exactly right, Alicia. We know that cancer and cardiovascular disease are such common clinical scenarios for all patients in the United States, but there's some particular emphasis in prostate cancer because of some of the shared risk factors that overlap between the two diseases, cancer and cardiovascular disease. So like you said, prostate cancer is a disease of elderly men in general. We know that they are at an epidemiologically increased risk for cardiovascular disease just by virtue of age and sex. And in addition to that, we know that prostate cancer can follow oftentimes a more indolent and protracted disease course, and so that can oftentimes play out even over many years, even for men with advanced prostate cancer. And so that certainly opens the door potentially for competing risks, like cardiovascular disease, in the population. And then again, like you said, our fundamental therapy that we use for men, from a systemic therapy angle, is energy deprivation therapy, which has been for over a decade now associated with a wide variety of potential metabolic and cardiovascular adverse consequences that put them at risk for cardiovascular disease.

Alicia Morgans: So can you remind everyone, what are some of the metabolic changes that happen in men when we lower their testosterone with things like androgen deprivation therapy, or whether that's orchiectomy or whether that's a pharmacologic approach?

Vivek Narayan: Sure. So there is a wide variety. But energy deprivation, regardless of the mechanism by which we're doing it, has been associated with certainly metabolic derangement. So that can include changes in your weight distributions or visceral adiposity. It can be associated with a dysregulation in insulin sensitivity or glucose intolerance. It's been associated with dyslipidemia, and also with some vascular changes like arterial stiffness. So really, a whole host of potential changes that all can lead to increased potential cardiovascular risk.

Alicia Morgans: One of the things that I think is also so interesting, and important for us as clinicians to recognize, is that so many men with prostate cancer actually, because as you said, of the shared risk factors, actually have at least one or two risk factors for cardiovascular disease and may have overt cardiovascular disease. How common are these issues in patients that you treat, in patients with prostate cancer?

Vivek Narayan: I think it's extremely common, and this is being born out in a number of studies now, both in clinical trial populations as well as in more real world analysis, looking at prostate cancer patients. In particular, prostate cancer patients who are planning to start energy deprivation therapy. And so I do think there's a high prevalence of these cardiovascular risk factors in the population. One example of that is the recent phase three clinical trial HERO study that was published in the New England Journal of Medicine this past year. And to my recollection, about 90% of the patient population had at least one underlying cardiovascular risk factor entering that study.

Our group here at Penn has also looked at this in a veterans population, so in the VA health system. And I think what we learned there is that not only is it highly prevalent to have cardiovascular risk factors in this population, but I think we also, as clinicians, could do a much better job at trying to actually look for and assess these cardiovascular risk factors. So we found that up to a third of patients who have planned to start energy deprivation therapy actually have not had adequate cardiovascular risk factor assessments, such as blood pressure testing, hemoglobin A1C, lipid panels, and so forth, to really find out what is the true prevalence in this population.

Alicia Morgans: I think that work that you did in the VA population is so important because of course the rates are relatively low, but that's in a system where there are reminders and there's a team management approach. And so if that system can't even really ensure that there's universal assessment of these risk factors, it's even harder when people have care in one system or another system, and are trying to navigate and negotiate between physicians across different health systems. How do you in your clinical practice find the best ways to try to approach these problems and to try to screen patients and ensure that they have adequate management and followup for some of the risk factors that can affect their cardiovascular health?

Vivek Narayan: I think it's definitely an evolving practice change, but we're fortunate that we work alongside some really experienced cardiologists who obviously have an expertise in the cardiovascular system and risk mitigation, but also have a special interest in cardio-oncology. So understanding some of the pertinent oncologic aspects as well that we have to take into context when managing these cardiovascular issues. And so we're very quick to seek their consultation for patients who we have a sense that they may be at some increased risk, either because of existing cardiovascular disease or because of elevated cardiovascular risk factors. Seek their co-management for these patients as we initiate ADT for prostate cancer.

Alicia Morgans: Absolutely. Well, and I guess as we start to wrap things up, just I'd love to hear your thoughts on the oral agents that we use, the androgen receptor targeted agents, the antagonists, or things like abiraterone that really just reduce testosterone levels by really interfering with the synthesis of testosterone. These agents also appear to have some cardiovascular risk, or maybe just compound that risk that we induce with the hypogonadism of ADT. What are your thoughts on that? How do you best navigate when you know that this is maybe the right treatment for the patient, but you also, of course, have these cardiovascular risks to consider?

Vivek Narayan: I think we certainly use a wide variety of these oral agents now. My sense is that they all have some overlap with their potential cardiovascular toxicities, but also some unique aspects to each agent that we have to keep in mind. In particular, what I've found to be most potentially problematic is that high levels of hypertension that can be associated with these agents, even upwards of 20% of patients having grade three or higher hypertension. And so it's really clinically significant. And so we certainly try to get patients to have adequately controlled blood pressures leading into this therapy. And sometimes, again, that requires some co-management with cardiology or nephrology providers. And then really close toxicity monitoring. So sometimes it's home blood pressure monitoring, or at least at the beginning stages, co-management and visits with our cardiology team.

Alicia Morgans: Absolutely. And thank you for bringing up blood pressure control, because that is such a clinically common occurrence, to see blood pressures creeping up. It is something that I monitor, actually, at every visit with my patients and always engage with them on it. And also, of course, encourage them to reach out to PCPs. And sometimes if things are really not going well, I reach out to the PCPs or their cardiologists myself. But I think that that's sometimes overlooked. With all our discussions about cholesterol or about pre-diabetes, sometimes we don't think about that, which is something that we can intervene on pretty effectively if we at least take that first step and recognize that patients have hypertension to begin with while they're on these medicines. So thank you.

So if you had to give an overarching message to clinicians who are caring for men with prostate cancer. And really trying to think anew about their cardiovascular risks or update their prior thinking, what would that be?

Vivek Narayan: So I think first and foremost, it starts with awareness. And so we have to, as a field, be aware that cardiovascular risk factors of disease is a true phenomenon in prostate cancer patients and one that needs to be adequately managed, especially in those patients who are being planned for androgen deprivation therapy. And I think for the research field moving forward, the question would be, how do we best identify and risk stratify these patients so that as we develop new tools to mitigate that risk, we really know the right population to use those tools in? Because we know androgen deprivation therapy is not going away, and it's such a fundamentally important part of our systemic therapy for prostate cancer.

Alicia Morgans: Absolutely. Well, thank you so much for sharing your expertise, for your wonderful article. Which, again, for viewers is really covering the gamut of GU malignancies and thinking about cardiovascular complications across all of them. I really appreciate your expertise and your time today.

Vivek Narayan: It was fun. Thanks, Alicia.