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Thomas Suter: It’s great to be here. I apologize—I’m only a cardiologist, not an oncologist. So I have absolutely no idea what you guys are discussing, but I’ll try to discuss quickly with you the concept of cardiovascular side effects of cancer therapies.

OK, so here we go. Now, I think most of you realize that when we talk about the lifetime cardiovascular risk, one of the most important factors are the cardiovascular risk factors. There are modifiable ones and non-modifiable ones.

And when we talk about the non-modifiable ones, what you appreciate from this graphic here is that the risk for cardiac disease sharply increases just at the time the prostate cancer patient will present to you. So it’s in the late 60s and the late 70s.

And the other thing, what you know, is the more cardiovascular risk factors the patient has, the higher the risk of cardiovascular disease. Can I have my next slide? I struggle here with advancing the slides.

So we had the opportunity to write guidelines on cardio-oncology on behalf of the European Society of Cardiology. And I would like to motivate you to look at them. I think they’re really important. And particularly the electronic version of it.

If you register on the ESC website, you can freely download it. And the beauty of this electronic version is it has a lot of calculators on it where you can assess the cardiotoxicity risk, not only for prostate cancer, but all cancer patients.

So please do this. Next slide, please. So when we talk about the cardiovascular side effects of systemic cancer therapy, there are quite a variety of side effects. Now, in regard to prostate cancer, the most important ones are hypertension, then myocardial ischemia, and cardiac dysfunction.

And a little bit less important is QT prolongation and arrhythmia. Now let’s quickly look at—next slide, please—let’s quickly look at the different drug classes that you’re using. Let’s start with the taxanes. Next, please.

So the taxanes for us, as cardio-oncologists, are not a big deal. They’re relatively safe. We don’t see much cardiovascular side effects. We have a lot of experience, not only from prostate cancer, but also breast cancer patients. And we have long-term follow-up in these patients. So they’re relatively safe. Next slide, please.

How about the PARP inhibitors? Well, it depends on which PARP inhibitors you’re choosing. The major issue is the induction of hypertension. But that’s something you can manage. So it’s not a big deal in my view. Next slide, please.

How about AKT inhibitors? They’re still young, from my perspective. QTC prolongation is an issue with some of these drugs causing arrhythmias. But again, I think we have to observe them more carefully. Next slide, please.

The big thing is really androgen deprivation therapy—ADT. And Dr. Ryan is going to talk about this more specifically. So I only want to quickly touch on ADT. Next slide, please. So one thing which is critically important when we talk about cardiovascular side effects of cancer therapies is that you understand the mechanism of the side effects.

And I would argue, when we focus on ADT, it’s actually a cardiometabolic problem. Next slide. So what that means is, when you treat your patient for prostate cancer and your patient already has cardiovascular risk factors, you’re actually adding insult to injury.

And I think it’s important that you understand that what you’re doing with ADT is actually modifying the modifiable risk factors—you make them worse. So you have to look at them and you have to manage them to get the best outcome for your prostate cancer patient. Next slide, please.

I show you this slide—this is actually from the guidelines—not to specifically discuss it, but just to give you an impression of what we try to convey here. You see the different drugs here listed. You see the profile in terms of inducing hypertension, in terms of increasing glucose, in terms of inducing heart failure, ischemic heart disease, and atrial fibrillation and QTC prolongation.

But the point I want to make here is, even within the same class of drugs, the profile—the cardiotoxic profile—is different. And you have to address this and assess this for every single drug that you’re using in your prostate cancer patient. Next slide.

So what are our recommendations? And we’re focusing now on monitoring and prevention. Our number one recommendation is that you assess the baseline cardiovascular risk of your prostate cancer patient.

So, how do you do this? You do this ideally with the SCORE2, or if you live in the United States, you can use the Framingham score. It’s probably more or less the same. And what you do is—next slide, please—you type in the risk factors.

I have done that for one of my prostate cancer patients. He is a 72-year-old Swiss, non-smoker, has type 2 diabetes, slightly elevated blood pressure, and elevated LDL. And when you put this into—and I use here the U-Prevent website. That’s the University of Utrecht website, which is great. I love it, I have to say. Next slide, please.

What you get is you get a risk assessment—a 10-year risk assessment. What is the risk that this patient will die because of cardiovascular complications, or that the patient will experience a heart attack or a cerebrovascular insult?

And what you can see here in blue, the risk for this patient is 22%. And the beauty of this U-Prevent website is that you can now play with what happens if I modify the risk factors of my patient. For example, I wrote in here, how about if I lower the LDL from 3.8 to 1.8?

How about if I treat the blood pressure to less than 140? How about if I treat this patient with aspirin? It’s great. Look, it reduces the risk of this patient by almost 10%. Number needed to treat is 10. Isn’t that great?

So what I’m saying here is we need to manage the risk factors of the patients to optimize the cardiovascular side effects in your cancer patients. Next slide, please.

What we also recommend is that you get an EKG. You want to know what is the QTC at baseline. Next slide.

More importantly, you want a baseline EKG for your patient. Why? Because you have a risk that you induce ischemic heart disease with your drugs. So you want to know if you have a change in your EKG. If you don’t have a baseline EKG, you don’t know. So you need to get an EKG. It’s cheap. It’s easy, but you need it. Next slide, please.

You need to measure the blood pressure in your patient. In a patient who has not established cardiovascular disease, you want the blood pressure less than 140/90. For the patient with diabetes, we want a blood pressure that is less than 135/85.

And in a patient who already has established cardiovascular disease, you want a blood pressure that is lower than 120/70. So here are your monitoring and your prevention tools. Next slide, please.

So, how do you identify the patient with ischemic heart disease due to your ADT, for example? Well, you know the symptoms. I don’t have to repeat them. EKG is important here. And then the troponins. In modern cardiovascular medicine, we need troponins.

But be aware, baseline troponin is not always zero. It may be elevated, for example, if your patient has renal insufficiency, your troponin is going to be elevated. So again here, you need a baseline troponin so that in case your patient gets into trouble, you can compare these levels. Next slide.

How about heart failure? Well, that’s a complicated one. Next slide, please. This is a syndrome you need to be aware of if your patient can’t do the stairs anymore, dyspnea on exertion, weight gain, and so on. You need to think of heart failure.

And here again, second, you need to assess the BNP levels. Same story like troponin. Not all the baseline BNPs are normal. Therefore, you need a baseline BNP so that you can compare. Same story.

And if you see that this BNP is now elevated, you need to get an echocardiogram on this patient, because it’s a completely different issue if this patient has heart failure due to reduced ejection fraction (HFrEF) or with preserved ejection fraction. Next slide.

So in summary, ladies and gentlemen, what we recommend in our cardio-oncology guidelines of the ESC is optimize the cardiovascular risk factors of your prostate cancer patients. Get a history and physical exam on this patient, including blood pressure.

Assess the cardiovascular baseline risk of your patient. Try to modify it when it is elevated. Get an EKG. Get the cardiac biomarkers—that is NT-proBNP and troponin. And in some selected patients, you might opt to get an echo. Next slide.

How are we doing? This is from the RADICAL-PC analysis. So that’s a group in Canada, Australia, Israel, and Brazil who looked at prostate cancer patients—2,800 consecutive patients.

And they looked at how these patients had their cardiovascular risk optimized. And you can see that 50% of these patients had non-optimized cardiovascular risk factors. So I think there is absolutely room here to improve. And I urge you, please do it.

And my last slide, please. So, what are the uncertainties in this whole story? Well, there are plenty, unfortunately. We don’t have studies where we specifically address the cardiovascular outcome in prostate cancer patients.

We have no long-term studies. And I think this is an important point, because what you modify with ADT, for example, is the metabolic profile of your patients. So this is a long-term effect on the cardiovascular health of your patients.

And we don’t know if the primary and secondary prevention tools that we’re having are effective. But we have so much data from non-cancer patients that it is very, very likely that if we modify these factors, we do good for our patients. Thank you so much for your attention.