Protecting Your Heart During and After Prostate Cancer
PCF’s Dr. Phillip Koo talks heart health with PCF-funded leaders in the field of prostate cancer survivorship: radiation oncologist Dr. Sagar Patel (Emory University) and medical oncologist Dr. Matthew Smith (Harvard University and MGH Cancer Center).
Even if you are not on hormone therapy, avoiding heart disease is part of your survivorship plan. The good news? It starts with awareness, and there’s a lot you can do.
- Heart disease is the #1 cause of death in patients with prostate cancer — more patients with prostate cancer die of heart disease than of the cancer itself, so heart health deserves equal attention alongside cancer treatment.
- Hormone therapy (standard ADT and the newer ARPIs) can raise cardiovascular risk — through weight gain, metabolic changes, and effects on coronary arteries. These risks are manageable and shouldn’t discourage patients from treatments that improve survival.
- Simple risk assessment goes a long way. Think of it as ABCDE through Awareness, tracking your Blood pressure and Cholesterol, knowing your Diabetes risk, and starting or continuing Exercise. Make sure you have a primary care provider monitoring these alongside your cancer care team.
- Diet, exercise, and open communication with your care team are your best tools — a heart-healthy diet is a prostate-healthy diet, regular exercise (including resistance training) helps offset treatment side effects, and most cardiovascular risks from treatment are preventable with awareness and proactive care.
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Transcript:
Phillip Koo, MD [00:00:00] We hear a lot about heart disease. We see about it all, like read about it all the time. What is heart disease? Because you know sometimes, I think patients think, oh if I’ve had a heart attack, I have heart disease, but we know that’s not true. It’s more than just a heart attack.
Sagar Patel, MD [00:00:14] Yeah, no. Phil, that’s a great question to kind of just set the stage, you know, I look at heart disease more as cardiovascular disease, any sort of insult on our heart function that limits the ability of the heart to perfuse or deliver blood appropriately to our peripheral organs, various parts of our body, including our brain, as well as having blood flow to the heart itself. So, any sort of disease that may compromise that even well before a heart attack can be attributed as heart disease.
Phillip Koo, MD [00:00:43] So if a patient is diagnosed with hypertension, high blood pressure, then that puts them into the heart disease category.
Sagar Patel, MD [00:00:50] Exactly, I mean, that’s one of our risk factors that may compromise the heart’s ability to push blood flow out to the rest of the body and high blood pressure definitely does decline that the heart functions that I would attribute high blood pleasure as a heart disease risk factor.
Phillip Koo, MD [00:01:06] And then why, you know, this is sort of a hidden risk in prostate cancer, so explain that to us and why does it matter so much today?
Sagar Patel, MD [00:01:17] So I think you hit the nail on its head when you stated the number one cause of death across all prostate cancer patients is heart disease. That’s across the board. Regardless of the stage of your cancer, if you’re diagnosed with prostate cancer, you’re most likely to die of heart disease, and that’s based on our statistics using kind of population-based databases of the United States patients. So, it’s really important to level up your cardiovascular health, your heart health at the same platform at the level as your prostate cancer management because based on the statistics, you’re more likely to die of heart disease. So, I think that’s where predominance, the importance lies.
Phillip Koo, MD [00:02:00] Great. All right. So Matt, we’re going to shift over to you and start talking about sort of this awareness gap Maybe in some ways it’s been a knowledge gap, but you know, we are very honored to support some of your work that’s led to the changes in these guidelines Can you talk to us about? Why this awareness gap and this knowledge gap exists?
Matthew Smith, MD, PhD [00:02:22] Yeah, so I think a lot of work supported by PCF has helped to close that gap, but it certainly still exists. Going back decades to the early part of my career and a lot of work supported PCF, I was able to participate with the research team to help define some of these risks or understanding the relationship between androgen deprivation therapy and side effects. At that time in the late 1990s, the view was, you know, ADT had side effects. It caused hot flashes and loss of sexual interest, for example. And that was kind of the end of the conversation. But, you know, as we dug into it deeper and other investigators dug into this deeper, it’s very clear that common treatments for prostate cancer, including androgen deprivation therapy, increased the risk for a variety of conditions, including diabetes and very likely cardiovascular disease. The reason we became interested in that is because outcomes for prostate cancer were improving, right? And we’re moving a lot of the therapies earlier into the course of the disease. So, while we’re improving prostate cancer outcomes and helping men live longer, they’re also living longer with a burden of more treatment. And so, understanding possible side effects of treatment was really paramount. And a whole series of studies over the course of time, population-based studies, metabolic studies, prospective clinical trials, all help to define some of these risks and to better understand strategies to prevent potential harms of treatment.
Phillip Koo, MD [00:03:52] So that’s interesting, and it’s great. It’s actually a good story because we’ve made so much progress. Patients are living longer, hopefully living better, and paying attention to issues like this become even more paramount. So, I think it’s just one of those things where there is real no-free lunch, but it’s how the field has evolved over time. So just stepping back from a clinical perspective, who owns this conversation? How does this dialogue occur because there are patients on our webinar right now who’ve lived with prostate cancer for years Some who might have advanced prostate cancer Some this is a completely new topic to them How do they start that discussion, or should they even start that discussion with their physicians?
Matthew Smith, MD, PhD [00:04:39] I think it’s super important that our patients become involved in that conversation, right, that they ultimately take ownership. But there are different models of care, right? In some settings, the primary care provider is going to be the leader in assessing these risks. That’s very commonly the case, looking at risk factors for cardiovascular disease, looking at strategies to reduce the risk of cardiovascular disease. In patients at particularly high risk, cardiologists may become involved and, in my view, the individuals providing oncology care, if they’re using medications that could increase a patient’s risk for the disease, you need to own that by acknowledging those potential risks and either managing them with the patient or appropriately communicating with the rest of the provider team. For example, the primary care provider to discuss those risks.
Sagar Patel, MD [00:05:35] Yeah, and I’ll add to Dr. Smith’s point that, you know, we’re fortunate, and at least in the US, that we have very excellent multidisciplinary care for our prostate cancer patients, which many doctors are involved in a patient’s journey. And I think the patient has to be their own advocate, which I think webinars like these help create awareness and education for these patients. But I think a lot of the awareness kind of needs to stem from a patient to bring up these conversations. But I definitely agree with what Dr. Smith said, that PCPs definitely, you know, manage a lot of these risk factors for patients. They often are a quarterback of a patient’s care. But because there’s so many doctors involved, the patient needs to be equipped and empowered to start these conversations in the clinic.
Phillip Koo, MD [00:06:22] And I think this is a really good takeaway point for all the patients and caregivers on the line. I think sometimes we assume behind the scenes all the physicians are talking to each other, they’re all on the same page, and we know that’s not always true, it’s just logistically very challenging. So, for patients to be able to connect the dots with their primary care physicians, their urologists, their radiation oncologists, their medical oncologists. Whoever that might be, and cardiologists, if necessary, to make sure they are sort of addressing these major issues. All right, so now we’re going to transition into sort of the risk factors, and we sort of talked about this already. Explain to us, Sagar, I’ll start with you. How is it that ADT, you know, leads to this increase in cardiovascular risk?
Sagar Patel, MD [00:07:11] Yeah, so, you know, a lot of the research we have kind of really stems as we mentioned from Dr. Smith’s seminal work over two decades ago, but you know I think it’s a multifactorial contribution of hormone therapy on cardiovascular risk. Historically we’ve attributed the cardiovascular risk from deep testosterone suppression, which results in metabolic derangement, weight gain, especially central adiposity or belly fat, insulin resistance or glucose intolerance. And those types of changes elevate an individual’s risk factor for developing heart disease, having higher blood pressure, higher cholesterol levels, and developing diabetes. And then more recently, with work that’s been directly funded by the PCF, we’ve actually identified perhaps a more direct biology from hormone therapy on cardiovascular risk, specifically that certain types of hormone therapy drugs may exacerbate coronary plaque progression. And that there may be a direct involvement of the drug itself on propagating coronary plaque, which again, diminishes the ability of blood to flow to the heart cells themselves and diminish its function of pumping blood to the rest of the body. So, I think it’s twofold. It’s multifactorial from an elevation of risk factors due to weight gain, metabolic derangement, and also a direct effect of the drugs on, for example, coronary plaques and atherosclerosis.
Phillip Koo, MD [00:08:34] So that’s real interesting. And then, you know, if that’s the case, we know that patients are on ADT pretty much throughout most of their journey in general. Are there differences if someone is on ADT earlier versus someone who has metastatic disease who’s on ADT?
Sagar Patel, MD [00:08:54] So I think a lot of it is that ADT initiation is a risk factor. So, if you have a patient who’s on it for a short term versus long term, I think generally speaking, we do believe that patients on longer term are at higher risk because that has more of an insult on their overall risk factors, including weight gain, metabolic derangement, et cetera. But even individuals who have a short course of hormone therapy, for example, if you’re pursuing the course of radiation and you require six months of hormone, therapy. You may still be at risk because of the direct attribution of the drug on, for example, coronary arteries and coronary plaque development.
Phillip Koo, MD [00:09:32] Great. So Matt, we focus a lot, we know the relationship between ADT and heart disease. So, if you’re not on ADT, do you not have to worry about this?
Matthew Smith, MD, PhD [00:09:43] Yeah, so it’s a perfect question because I wanted to say, we kind of jumped to the side effects of ADT, but to be fair and balanced, we have to also comment that we’re using these drugs in settings for which they’ve been shown to improve survival for the most part. So, it’s important for everyone, physicians first and foremost, but patients as well to understand why is this recommendation being made to add ADT to radiation, for example, for intermediate or high-risk disease or to use it as the mainstay of treatment for metastatic disease. It’s based on very strong evidence of improved outcomes. And I would say, despite what we now recognize are the possible side effects for some patients. But here I’ll talk with my hands, right? So, if a patient, you know, it isn’t like turning on and off a light switch, right. Like it isn’t like someone has no risk and then you give ADT and they have risk or other androgen targeted therapy. So, patients come into treatment with a certain amount of risk and then we may increase it by further by the unintended effects of the androgen deprivation therapy. Accordingly, patients who don’t require ADT are also at risk. And much like we said that, you know, men with prostate cancer are more likely to die of cardiovascular disease than of prostate cancer, that’s true regardless of ADT. And so, if you’re at lower risk prostate cancer such that you never require ADT, then you really have to consider the potential risks of other causes of morbidity and mortality. I think it’s well documented in social sciences that humans are very bad at evaluating and sizing risk, right? Like, we all know people, they’re very worried about dying in an airplane crash as they drive dangerously down the highway without their seatbelt on. So, they’re misunderstanding the risks involved of their behaviors. And similarly, I think. The word cancer is so scary to some patients that they sort of forget about the other factors that could influence their health. And here we’re focusing on a very important issue of cardiovascular disease.
Phillip Koo, MD [00:11:49] So, you know, there’s a lot of different medications now available, different formulations. For ADT you have injectables, you have orals, you’ve agonists versus antagonists. I mean, even for myself and for all the patients online, it gets really confusing. So, what sort of goes through your head when you’re prescribing these medications for patients and how do you sort of assess and figure out which one’s best for them?
Matthew Smith, MD, PhD [00:12:15] Maybe I’ll take the first part of that just and then leave the other part to Sagar about the agonist versus antagonist and the rest of it too. But the first, I think big picture, you got to zoom out and say, why are we recommending this treatment and does the age and health of the patient alter that calculation? So, we have national guidelines that might say, add ADT to radiation, for example, for intermediate, unfavorable intermediate risk disease. But if it’s an older gentleman, who has known severe coronary artery disease, maybe that calculation is different and you might choose to omit androgen deprivation therapy because the potential downsides of such treatment would outweigh any potential benefit in a very specific scenario like that. So, I think we also have to think about the age and health of a patient in terms of their expected mortality and the comparative risk of their cancer. So, considering the overall health of the patient’s, extremely important, just making fundamental, frontline decisions about what the recommended treatment is. And then further, if you decide that treatment, including systemic therapy with ADT is important, then you need to think about what’s the optimal form of treatment? Does that impact recommendations about duration of therapy? And certainly, as we’ll get to more, like what are the other considerations about monitoring and preventing potential harms of treatment.
Sagar Patel, MD [00:13:40] Great, yeah I’ll pick up where Matt left off in terms of specific drug types that you know there’s been emerging data over the past five to six years that there may be a difference in risk based on specific hormone therapy drug types specifically for example a gonadotropin releasing hormone or GnRH agonist versus an antagonist and we have drug formularies for each of these types of drugs and its controversial we’ve had conflicting data. Maybe one shows that an antagonists may have lower cardiovascular effect than an agonist and leuprolide being a common agonist we prescribe. And the data is murky and it can be quite conflicting. Recent data that the PCF has helped supported suggests that an antagonist may diminish the coronary atherosclerotic effect of hormone therapy compared with an agonist. There’s limitations to this emerging data, but I think all in all, there’s pros and to each of these drugs. From a cardiovascular standpoint, I’m personally a believer that there is a difference in risk. And for certain individuals who are having multiple cardiovascular risk factors, but have or need ADT for their prostate cancer, I do consider utilizing these, an antagonist or these newer forms of hormone therapy drugs.
Phillip Koo, MD [00:15:01] You know, I think this is a really good moment just to step back and for patients to recognize it’s such a complicated topic. And when you make the decision that you need ADT, you could see how complex it gets. It’s the type, the formulation, the frequency, duration, a lot of these come into play. So, I wanna make sure the patients initiate those conversations and are getting the answers that they need. And I think there are a lot of tools online that help you with information, but that interaction you have with your provider team, your physicians is vitally important. And just make sure you feel comfortable with the explanations you’re receiving. And if not, ask more questions. So, this question has come up a couple of times. You know, we’re talking a lot about ADT. We haven’t talked about the ARPI drugs and their risks, contributions to cardiovascular risk. But is there any direct correlation between the prostate cancer itself and heart disease? You know, we hear a lot about sort of inflammation in the body that might be the cause of cancer and heart disease. I think it’s more of a hypothetical question, but I’m just sort of interested to hear what you guys know and think
Sagar Patel, MD [00:16:12] Yeah, I mean, I’d love to take an initial thought on that. So, you know, some of the research that our group has done, again, directly supported by the PCF, has suggested that there is a bidirectionality of your prostate cancer and heart disease. And as you mentioned, Phil, this may be due to a systemic inflammatory response that cancer burden heightens our body’s innate immune response across the board. And that immune response may impact our coronary arteries or our heart muscle cells themselves. So, what we’ve seen in our initial data is that perhaps men who have higher risk prostate cancer, meaning higher Gleason scores, higher PSA, a higher stage within the prostate, they have higher baseline coronary artery disease independent of other risk factors, which suggests maybe the burden of cancer, prostate cancer may have a direct correlation with the burden heart disease in their body.
Phillip Koo, MD [00:17:11] Matt, any thoughts?
Matthew Smith, MD, PhD [00:17:12] No, I’d say, I think it’s really super interesting observations that Sagar just pointed out, and I hope that there’s a lot more work done to look at this in larger data sets to really better understand this, because I think you could really be onto something very important. But it’s just a further reminder that if you’re diagnosed with prostate cancer, it’s a teachable moment, not just to address the cancer itself, but to really consider the other health risks that may accompany that disease also being attended to.
Phillip Koo, MD [00:17:39] You know, I think this is always so fascinating how complex it is, and oftentimes, I’m sure you guys experience the same thing, we get these questions and people want sort of binary yes or no answers, and there really is no simple answer oftentimes, and it’s still an area that needs to be looked at, and that’s why I think research is so important to all of this, to help unlock these questions that we have. So, we’re going to go on to assessment and care team coordination. So, Sagar, I’m going to start with you because I know we funded a project looking at risk stratification. You know, patients, when they’re diagnosed, they’re going to see usually a urologist, they’ll see a RadOnc. Obviously, you need to be in good heart health to undergo surgery. But just sort of talk us through this risk stratification, risk assessment for patients regarding their cardiovascular health early on at initial diagnosis.
Sagar Patel, MD [00:18:34] Yeah, so, you know, I think when we see a new patient in the clinic with the diagnosis of prostate cancer, we hyper-focus on their cancer and risk stratify their cancer and tailor our therapies around that. But it’s very important for your provider to also do a stratification of your cardiovascular risk factors. And it can be quite simple. You know, we have a mnemonic, an acronym A, B, C, D that we think about, or at least I think about my clinic. A, standing for awareness. B standing for blood pressure, C standing for cholesterol or lipid levels and D standing for diabetes assessment. So, if you can take B, C and D and basically address those basic cardiovascular risk factors, hypertension control, lipid control and making sure you’re not at risk for diabetes or if you are, you’re on appropriate medications to optimize, then that’s a basic assessment that I think every patient deserves regardless of what risk of prostate cancer you have and regardless of what therapy you’re about to pursue.
Phillip Koo, MD [00:19:34] So, Matt, I’ll turn to you. You often see patients more with advanced disease. How do you sort of look at cardiovascular risk? How do assess these patients? How do sort of figure out where they fall in and how does that impact the treatment choices that you have to make together with patients.
Matthew Smith, MD, PhD [00:19:53] Yeah, in our model of care, just to say, I see patients across the entire spectrum of disease. I only see prostate cancer. So, from early-stage disease to metastatic disease, obviously medical oncologists are more commonly involved or most commonly involved in quarterbacks for care in patients with more advanced or metastatic disease. But the issues are the same. Clearly like the proportional concerns are different, right, for someone diagnosed with the de novo high volume, high grade metastatic disease. The priority is treating the cancer, cardiovascular and other health considerations are still important, but maybe less important than a patient of similar age diagnosed with unfavorable intermediate risk localized disease. So very different considerations in that regard. I’d say that I incorporate this as part of my initial evaluation of patients, have that conversation with patients. And I’d say, you know, and we talked about this in preparing for the call today, is like a lot of times we find information in the course of the workup that leads you down this path. Like, so for example, PSMA PET CTs were forever getting reports that say, you know severe coronary calcification incidentally noted on the scan. And then you have the conversation with the patient, like were you aware that you have coronary artery disease? They say, absolutely not. This is the first time anyone’s ever told me that. So that, this is a very common finding, it happened today this morning when I see patients in clinic, you know, pointing out to this very fit, athletic 70-year-old man that he has coronary artery disease based on his PSMA PET CT scan that shows coronary calcifications. So that initiates an important conversation about additional strategies to mitigate risk.
Phillip Koo, MD [00:21:39] You know, I think that’s a great point. And for all the patients on the line, you have access to your radiology reports. And oftentimes, there’s a section that they’ll say heart or cardiac, and they may or may not comment. But if there is a lot of calcifications, they should be commenting on that. And that’s a trigger where you can take some action to take control and bring up the topic of cardiovascular health with your physician teams. So, we haven’t talked about ARPIs. So that’s like the abiraterones, darolutamide, apalutamide, enzalutamide, what do we need to know about that with regards to its effects on cardiovascular health? And Sagar, I’ll start with you.
Sagar Patel, MD [00:22:21] Yeah, yeah, I’m happy to take an initial stab and then this is this is Matt’s wheelhouse being a medical oncologist and what he routinely prescribes. You know, from my thoughts, I personally don’t directly prescribe these. I refer these patients to our medical oncologists like Matt to oversee these. But what we do know from the data is that the inclusion of second-generation hormone therapies or ARPIs like the ones you mentioned, they do exacerbate cardiovascular risk, including hypertension or blood pressure and the risk of major adverse cardiac events like a heart attack or a stroke. We know that through really good, robust, prospective data, including drugs like abiraterone, which is more commonly used, even in patients with localized, high-risk prostate cancer compared with metastatic. So, my thoughts from my standpoint is that these drugs are very powerful. We’ve really pushed the needle in terms of curability for prostate cancer with these drugs. We’re utilizing them earlier and earlier, and I think as the field moves forward, probably sooner and sooner in these patients, but they can exacerbate risk. So, if you are pursuing a second generation on top of basic ADT, your risk may be higher, and it’s definitely worth starting that discussion with your providers.
Phillip Koo, MD [00:23:32] I think that those are great insights. Matt, from your perspective, there’s some questions and always a lot of discussion about intermittent ADT. How does that affect cardiovascular risk and sort of how do you approach the idea of continuous versus intermittent and figuring out where to give breaks and does it even matter?
Matthew Smith, MD, PhD [00:23:49] Before I answer that, I just wanna add one thing about the ARPI. So, I would say I completely agree with what Sagar said that we have good data from randomized controlled trials that these drugs increase the risk for cardiovascular events. That said, those same randomized controlled trial were done for the primary purpose of evaluating efficacy and ARPI’s have been transformational in the field. So, I don’t want the audience to leave this meeting thinking like ARPI is bad. It’s really quite the opposite. They’ve transformed the field of prostate cancer and have shown consistent improvements in progression-free and overall survival across almost the entire spectrum of prostate cancers. Sagar raised a really great point, which is as we move the drugs earlier and earlier, we are gonna find the point where we are not doing more benefit than harm. We may have found it already, but the common settings for which guidelines recommend use of these drugs, it’s very clear that they improve progression-free and overall survival. We may be pushing those boundaries as we move the drugs earlier and earlier, but certainly in patients with metastatic disease, been transformational, and I think account for a lot of the improvements in prostate cancer outcomes over the past decade or so. Intermittent therapy is another, so we sort of push and pull, right? We’ve intensified therapy by giving two or three drugs instead of one. And in other cases, we try to deescalate therapy by doing what you mentioned, Phil, which is the intermittent ADT. So, this is really in the domain of patients who have less serious forms of the disease, not high risk, high volume, de novo metastatic prostate cancer, but recurrent disease after treatment with curative intent. So, despite having surgery and or radiation therapy, patient then has a rising PSA, may or may not have detectable disease on imaging, and is at lower risk for serious prostate cancer outcome, but there’s enough concern to recommend treatment. So, there are settings there where we would do intermittent therapy, typically treat a patient for one year with systemic treatment, ADT, with or without an ARPI, and provided they have an excellent response, discontinue treatment, and then resume treatment when their cancer progresses sometime later. And with that approach, some patients can be managed most of the time being off treatment. It’s not for everybody. And it certainly can improve quality of life because while you have a normal testosterone, you don’t have the side effects of ADT. But I’m really intrigued by Sager’s work where it shows that sort of that initial systemic therapy can promote plaque progression. I don’t know that we have data to say that it regresses when you come off treatment. I would suspect it does not. And whether those cyclic on-off effects is actually better for cardiovascular disease I think remains to be tested.
Phillip Koo, MD [00:26:40] Great. Fabulous. So now we’re going to transition to, okay, whether you’re low risk or higher risk or whatever it might be, you know, maintaining heart health is critically important. And I think we’ve established that. Now we’re gonna go towards sort of transition into this idea of managing risk. And, you know I think we can’t say enough. Matt, I’m glad you brought it up again. This is a story of success. The fact that we’re here today talking about this means and patients are living longer and better, it means the drugs that we’re doing are working. We’re just trying to find ways to, again, find that sweet spot and this is why medicine is always so fascinating. So now we’re gonna talk about managing risk and the hot drug these days are the GLP-1s and we know for a lot of patients who might be overweight or looking to lose weight, GLP-1s are being prescribed very, very commonly. In the setting of cancer, there’s always some questions because maybe there’s a loss of muscle mass or whatnot. You know, Saiger, I’ll start with you and Matt, I’d love to hear your thoughts on this as well, just because it’s such a hot topic. But Sigar what are your thoughts on GLP-1s?
Sagar Patel, MD [00:27:44] Yeah, I mean, GLP-1s have been revolutionary for endocrinologists, cardiologists, primary care physicians, just as second-generation drugs have been for us as prostate cancer providers. It’s really impacted us, our population as a whole. We’ve seen remarkable benefits in the general population. I’m seeing more and more patients in my clinic on GLP-1 agonist for various other reasons, whether it’s cardiovascular, diabetic control, or just pure weight loss for high BMIs. I encourage patients to maintain on those drugs because I postulate that there may be a benefit for patients who are on those while they receive hormone therapy or pursue their prostate cancer journey. And there may a protective effect on their cardiovascular risk. I think it’s to be determined that direct effect, we don’t have great studies to date that have really validated that, but I encourage patients to remain on it. I think that the data and the general populations It’s very reassuring, it’s very exciting, and I think that it may have a benefit in our prostate cancer patients, in particular the ones who receive and start hormone therapy.
Matthew Smith, MD, PhD [00:28:53] Great, Matt, your thoughts?
Matthew Smith, MD, PhD [00:28:54] I agree with Sagar and take much the same approach in my own practice. I don’t personally prescribe GLP-1 agonists but encourage patients to either continue if they’re already on them or have that conversation with their primary care doctor. I would add this is universal guidance for patients on GLP 1s because they reduce appetite and caloric intake. The quality of the calories is more important than ever. So sufficient protein intake in particular, and resistance exercise training, because the concern is that you can get kind of a starvation phenotype, which is you lose weight, but you also lose muscle. And so, patients on GLP-1 agonists, and the rest of us, should be following a very healthy diet and exercising regularly. That becomes even more important for those on GLP-1 Agonists. I’d say it’s a double concern in patients on ADT, because we already know ADT causes fat accumulation and muscle loss. So, if you then take a drug that causes muscle loss and fat loss, then the net effect is you could have very severe muscle loss, I don’t know that to be true, but I think it’s just a reason to be thoughtful about that and it wouldn’t discourage appropriate patients from taking GLP-1 agonists on ADT, but to be particularly mindful about the importance of healthy nutrition and regular exercise to maintain muscle mass.
Phillip Koo, MD [00:30:21] Great. So Matt, you brought this up a little earlier. What’s your approach to monitoring patients while they’re under your care, receiving prostate cancer treatments for these cardiovascular side effects? Or is there even a standard protocol?
Matthew Smith, MD, PhD [00:30:38] Well, in my practice, I mostly delegate that to primary care providers. So, I have a conversation with the patient, communicate with the primary care provider. I think in busy oncology practices, it’s very difficult to take on like all of the aspects of primary care. So, I collaborate with primary care providers to do that. And I try to be very clear in my communication with patients about that too. Like so, for example, the example I gave of this morning, and this happens every week, of like you have coronary artery disease, I can see that on your PSMA PET CT, that leads to, you know, an email to the patient’s primary care provider, a very clear conversation with the patient so they know the right next steps to take. The other thing I’d say is that a lot of the drugs that we use to treat prostate cancer interact with commonly prescribed drugs, including antihypertensives, statins, blood thinners. So those are really important things to consider as well. And so, and you certainly don’t wanna be discontinuing those medications in patients. Like for example, a statin, there’s a lot of interactions with statins and the ARPIs. So, you wanna be very mindful about continuing appropriate medical management of say elevated cholesterol in patients who require an ARPI.
Phillip Koo, MD [00:32:02] Yeah, and we all know that gets really complicated, so I love that, you know, it’s a must do. That coordination between primary care and the oncologist, whoever it might be, is so critical to making sure all of your medications are managed correctly and so that they stay effective. Sagar, I’m gonna ask you this question about multidisciplinary care, which you brought up. There are so many different team members and these days we can talk about nutrition we can talk about physical therapy you know exercise we have supportive oncology we have you know psychology you know to deal with the stress we have other support you know systems out there including cardiology and cardio oncology which is a growing field how do you figure out when best because it’s a these are limited resources how do sort of create a strategy and what advice do you have to patients to figure out when more higher level resources need to be brought onto the team.
Sagar Patel, MD [00:33:03] Yeah, it’s a great question. I think, you know, Matt and I practice in settings where we’re well equipped with these multidisciplinary experts in their various niches. So, we have cardio-oncology at our hand that I can refer to, but the reality nationally is that a lot of medical centers don’t have those capabilities that we do have, you know the point person being the urologist, the medical oncologist, the radiation oncologist and we rely heavily on the PCP. From my standpoint, it really goes back to risk assessment, and it doesn’t have to be complicated. Like I mentioned, the ABCD kind of format, it’s just overviewing each of those risks, your blood pressure, your cholesterol, your diabetes risk and making and assuring patients have a PCP that they follow and making and allowing and bridging that gap if they don’t. If they do have a PCP and they’re optimized on medication, but they have imaging features like Matt mentioned on a PSMA PET that shows really bad disease. I think that may buy the patient a referral to cardiology or perhaps cardio-oncology if that practice has access to one. So, I don’t think there’s not a clear-cut recipe for this. I think we haven’t harmonized our approach across the country, but it does involve your provider, whoever it may be, whether it’s the surgeon or the oncologist, to have some basic risk assessment. Ensuring you do have continued PCP follow-up, and if your risk seems to be elevated despite that, then perhaps referral to cardiology or cardio-oncology.
Phillip Koo, MD [00:34:40] And I think that’s a great point for all the patients and loved ones on the line. It’s a conversation, if you don’t feel comfortable, you know, bring it up. Maybe suggest, hey, I’d like to see a nutritionist you have, someone you’d recommend. So now we’re gonna transition into what patients can do to sort of take control as much as possible for their journey along this path. So, lots of questions, lots of topics that we could discuss. Let’s first start off with nutrition. And I do want to give a disclaimer, you know, both of you are not nutritionists and it’s a whole other specialized area and we’ve actually funded a lot of research on nutrition with people who specialize in this, but given the fact that you guys both see so many prostate cancer patients, what advice do you give patients regarding nutrition and diet? Matt, I’ll start with you. You know, I think the vegan diets, vegetarian, Mediterranean, all these different things are out there, different options. What advice do give to patients?
Matthew Smith, MD, PhD [00:35:37] Yeah, so at a high level, I’m reminded of a museum exhibit I saw years ago, and I give this anecdote to patients, and it had pictures from different families throughout the world with a week’s worth of food on their dining table, and the differences that you saw between these different ethnic, racial population groups were just so wildly different, it’s stunning. But that’s how you should think about nutrition. Like if I say to people, tell me about your diet and they’ll often I’ll get the answer with they’ll tell me what they ate for breakfast. That isn’t what I meant. Or like I eat a healthy diet. I had a salad for dinner last night. I’m like, that really doesn’t tell me anything. So, you need to think about the totality of what you’re eating. And it’s also your diet is not what you don’t eat. It’s actually what you do eat. And I think that we have a big problem in the United States and elsewhere about this, you know, this fad diet concept, you the idea swing. And having prostate cancer often leads to some big changes in the way people think about their health and improve their diet. And I that’s great, but you wanna find something that’s gonna be a sustainable approach. Very few people are gonna, there aren’t very many vegans in the Unites States because most people aren’t willing to do that. I was vegan for a couple of years and enjoyed that time, but then the pandemic came and I’m no longer vegan. But all kidding aside, so you got to think about all of what you eat, you have to think about nutrition as not a choice, but a series of choices, and you try to maximize that. And if you make it painful for yourself, you won’t continue it. And it’s also got to be a group effort in terms of the household where you eat. It can’t be your diet, and your spouse eats something else, and your children eat something different. It’s got to be a plan that works for you. And I’d also add another, just a very high-level comment is you got to think about the totality of what you eat. It’s lots of choices. And you don’t have a prostate diet, and a heart diet, and a diabetes diet. You have your diet. Now the good news is that for the most part, They appear to be pretty well aligned the eating behaviors, the nutritional behaviors that would reduce your risk for cardiovascular disease are also probably good for prostate cancer and certainly good for diabetes prevention. So fortunately, it’s pretty well-aligned. But commonly, I get the question, I’m sure Sagar does too. It’s like, now I have prostate cancer, what should I be eating? And I’ll say, well, what were you eating before? You don’t suddenly have a prostate cancer diet, you have your diet, and fortunately, it’s pretty well harmonized in terms of what would be good for both cancer prevention or delaying cancer progression, reducing risk for diabetes and heart disease.
Phillip Koo, MD [00:38:40] You know, I agree with that, and it’s interesting. Whenever people ask me that question, I always sort of respond that heart healthy is prostate healthy, and you’re right. It’s cancer healthy in general, and there is a lot of that overlap. Sagar, from your perspective, anything to add? And then additionally, if you could comment on nutritional supplements. You know obviously, there’s so much written, there’s a lot of things, I don’t think they’ve really been proven, but what advice do you give patients on supplements as well?
Sagar Patel, MD [00:39:06] Yeah, it’s a great question. So, I’ll add nothing major to add on to Matt’s remarks on his general diet. I just wanna highlight that point that I think it is what you just said, a heart healthy diet is a cancer healthy diet and harmonizing that is quite easy. And as Matt pointed out, making sure the whole household buys in, it’s very challenging for one individual to have a separate kind of menu of the day versus the rest. And the good news is that a heart-healthy diet benefits all, especially if you have prostate cancer and especially if don’t. So, I think that that’s easy for a household to adopt and a diagnosis like this can be very scary, but this is an opportunity for transformation in the household to improve everyone’s health. In terms of supplement. That’s a very very emerging topic I get a lot of it in terms lycopene, soy, all sorts of other over-the-counter supplements you can take how it impacts. In my own personal practice, I’m usually very clear with my patients that I have not seen any evidence that gives us a strong indication that any of these supplements really impacts their overall health and care. And I stick to the basics, keep a heart healthy diet and stay active and exercise. You’re doing all you need to. There’s emerging data that I’ve caught wind of, specifically around soy or lycopene that may have some positive attributions against prostate cancer. But me personally, I’m not aware or familiar or know if there’s any data that’s strong enough for me to make a strong recommendation to patients at this time. I’m curious if Matt, you do or you’re aware of anything.
Matthew Smith, MD, PhD [00:40:41] Yeah, so this comes back to like the zooming out the big picture of like, what are you actually eating? And what did our healthy ancestors eat? It’s whole food, right? Like it’s not supplements. And so, I emphasize to patients that like, spend your money in the produce section, not in the supplement section of your local grocery store. The supplements I recommend are a multivitamin and vitamin D, end of story. Like, and the rest of your nutrition, you should really be getting through whole foods, you know, unprocessed foods as to the best of your ability. And that involves spending money in the produce section, not the supplement section.
Phillip Koo, MD [00:41:25] I think that’s a great take home message for everyone listening. Sagar, we’re gonna shift to exercise, which we talked about GLP-1s, we talked the importance of resistance training. What counsel advice do you give to patients regarding exercise, especially since you see, actually you see patients along the whole spectrum, at initial diagnosis and later on for metastatic disease as well.
Sagar Patel, MD [00:41:47] Absolutely. So, this this whole abbreviation acronym, I bring back ABCD, the E that follows after the D for diabetes is exercise. I think that’s a huge patient-controlled factor that can be employed. It’s extremely important for a multitude of reasons. On an overall scale exercise obviously has a positive impact on our cardiovascular health. And it has in my belief a protective impact on treatment related cardiovascular risk as well. And secondarily, in my patients who I see are very active, who do exercise, who stay ahead of it, they actually tolerate day-to-day the hormone therapy detriments better than those who have a more sedentary lifestyle. So, I think overall, in a big picture, exercise is extremely important to improve your cardiovascular health, improve your long-term outcomes and survival. And then two, from a day-to-day pragmatic standpoint, I see that patients have a better tolerance to these therapies. For example, hormone therapy when they are more active and have a regular exercise routine.
Phillip Koo, MD [00:42:52] I think that’s so important for patients to hear that exercise is so helpful and reduces stress as well, which we know that it’s a stressful time. You know, we are very fortunate to have Matt Smith who did the seminal work regarding bone protection, you know, the importance of bone health. The question that’s asked often is, how do I manage exercise if I have weak bones or perhaps metastatic disease that involves my bones? What advice do you give to those patients, Matt?
Matthew Smith, MD, PhD [00:43:19] So it’d be very unusual that your patient’s bone metastases or risk for osteoporosis would preclude them from doing exercise. So that’d be a very special situation. I don’t put any restrictions on patients in terms of form of exercise. I do encourage my older patients not to begin repairing their own roofs and things if they weren’t already doing that before getting up on tall ladders, but that’s sort of just common-sense advice. Exercise, super important, completely agree with what Sagar said. Find something that you like to do and do it almost every day for exercise. Like there is no optimal form of exercise, the optimal form of exercise for the individual patient is what they will do on a consistent basis and preferably do it on most days. Because if exercise is something you might do, should you have extra time, it means you won’t do it. So, let’s be just very clear about that. You know, the best way to form habits is to just do things on a consistent basis. So, you should be exercising almost every day.
Phillip Koo, MD [00:44:21] So then what advice do you give to patients regarding the aerobic exercise versus weight training?
Matthew Smith, MD, PhD [00:44:29] That’s the personal part of it. So, I stand by what I said, which is do something that you will do. Like I’m a runner, a lifelong runner, so that’s great for me. I don’t particularly enjoy resistance exercise training, but if I were on ADT, I would definitely do more resistance exercise training because of the concern about muscle loss specifically.
Phillip Koo, MD [00:44:50] Yeah. Great. You know, we do have resources on the PCF website regarding diet and exercise. We also have a new heart health fact sheet that we just published and another manuscript that we’ve just supported talking about a lot of these topics. Sagar, how do you sort of counsel patients on the importance of exercise and any sort of tidbits that might help patients today?
Sagar Patel, MD [00:45:16] Yeah, I mean, I’ll reiterate some of the points that Matt said that I completely agree with. I think doing something that you can stay consistent with and doing it almost every day, five to seven days a week is very important. I personally like to encourage patients to have a balance between aerobic kind of cardiovascular endurance training, whether it’s running, biking, long walks where you’re going at a brisk pace for at least 20 minutes a day is important but incorporating two to three times some weight bearing exercises. With your upper extremities and lower extremities. We know that muscle mass has a positive effect on longevity and having muscle mass as you get older is protective for your overall health and improves your metabolism. So, I personally encourage a little bit more weight training activities. Now it doesn’t need to be deadlifting 450 pounds. This can be light weights but doing some sort of resistance to your upper and lower extremities is important, especially as Matt said, if you’re pursuing hormone therapy.
Phillip Koo, MD [00:46:13] Great. So, before we get into closing comments, we’re going to get into an area that’s a little bit more controversial, or an area we don’t know as much about. And Matt, it’s about estrogen, estradiol. We’re hearing more about this in the news. We’ve talked a lot about ADT. It’s not approved in the U.S., my understanding. Where are we headed with this estradiol with regards to prostate cancer management.
Matthew Smith, MD, PhD [00:46:42] Yeah, I worry a little bit about the evidence from estradiol. So, I mean, without a doubt, ADT with estradiol, going back in time, like this was the original form of ADT when it was given orally at higher doses, was quite unsafe, caused cardiovascular disease and thromboembolic events, and then went away. And we have GnRH, agonists and antagonists. And now we’re back with transdermal estrogen as an alternative form of ADT. Certainly, it would protect bone. Because estrogen is an important hormone in bone metabolism. But we have other non-hormonal ways to protect bones. So, I don’t think that that’s like a sufficient reason to give estrogen as an alternative. And while the study that was done in the UK was relatively large, I’m not sure it was adequately powered to understand small potential risks for serious lower rate events. So, I’m still very cautious about that. And it has different side effects, right? Like, so it can cause breast symptoms and other things. So, you have less hot flashes, better bone health, but other symptoms. And I’d say some possibility of unmeasured adverse effects because of the sample size of the study that was done. Well done study, but we don’t exclude all the possible harms is what I’m trying to say.
Phillip Koo, MD [00:48:04] And that’s where I think it’s important for patients to realize a lot of these studies are, you know, well designed, but they can’t answer every single question. So, I think here there’s clearly, you now, I think we need to learn more. And this is where hopefully PCF can continue funding more studies to answer some of those questions. There was a question about ADT 24 months. I noticed a trend, there is a lot more discussion, a lot in the meetings about, you know, sort of re-looking the duration of ADT shorter courses and perhaps more intermittent therapies. We’re gonna go to closing comments. Sagar, I’ll start with you. Just give us some, your closing thoughts and perhaps some other pearls that you might wanna share with the audience.
Sagar Patel, MD [00:48:44] Yeah, I think one point I was kind of itching to reiterate, which Matt brought up, is that ADT has been transformational for prostate cancer. It’s really revolutionized our care. We’re getting better ADT hormone therapy drugs on the market and for many patients, that’s extremely impactful. So, I hope this conversation doesn’t deter patients or make you wanna go to your providers and say, why am I on hormone therapy? Look at the risk. No, ADT as remarkable effect and benefit for prostate cancers, but it’s just important to have awareness because a lot of the risk factors and secondary effects, for example to your heart, can be prevented through appropriate medical optimization, through blood pressure control, cholesterol control with the statin use if you require it, and making sure you are protected from getting diabetes or if you have diabetes, you’re appropriately optimized as measured by your hemoglobin A1C. So, I think from this conversation, I just want patients to know that awareness is number one, asking a question to your doctor. And recognizing that these effects we’re discussing today can be prevented through just basic medical optimization, a large kind of push for that is just bringing up the conversation to your providers and then it can kind of go from there.
Phillip Koo, MD [00:49:56] Great Matt, final words
Matthew Smith, MD, PhD [00:49:59] Beautifully said, I’ll just add a very little to add to those great closing comments, really. I just say, just bear in mind that the treatments do have well-established benefits, like Sagar said. The potential harms we discuss are not inevitable. So, some patients come to me thinking that like, if I have ADT, that means I will get the following things. It’s not true, they’re possible harms. And as Sagar nicely pointed out, mostly preventable. So that’s the super important part to note. But to prevent them, you have to acknowledge them and understand the risks.
Phillip Koo, MD [00:50:31] These are great closing words. They’re preventable. So hopefully everyone on the line learned something today and has something more that they are equipped with to have that productive conversation with their care teams. And again, it’s preventable, so it’s a day where we celebrate success that we’re having this conversation. And we appreciate having both of you to enlighten us about this very complicated but encouraging topic. So, appreciate it and until next time.
Sagar Patel, MD [00:50:58] Thank you so much, appreciate the opportunity.
Matthew Smith, MD, PhD [00:51:00] Thank you, take care.