Alicia Morgans: Hi. I'm so excited to be here at APCCC 2022 in Lugano, Switzerland, where we've convened a panel to talk about complications of survivorship and how we support patients who are being treated with ADT for their prostate cancer. I have here Dr. Fred Saad, Dr. Tom Beer, and Dr. Chuck Ryan all really expert in this aspect of care for men with prostate cancer. Thank you so much all of you for being here. So let's start with bone health. I think this is an underappreciated area of care for men with prostate cancer and Dr. Saad, you certainly are an expert in this particular aspect of supportive oncology.

Can you tell us a little bit about the importance and what we should be thinking about for men on ADT?

Fred Saad: Right. So, so men who are going on to ADT and we're casting them to treat their prostate cancer, and we're doing an extremely good job. And now we have treatments that are doing even better to keep patients alive. So this problem accentuates itself. So when we give ADT, we castrate men, there's a certain amount of bone loss, especially in the first year, but it continues forever. Even if we do intermittent, we're continuing to lose bone. People get this impression that if we stop and we restart. But the fracture rate we're recognizing already years ago that it was quite high if patients are on ADT for any amount of time.

But now men are on for 10 years and it's about a 50% fracture rate at 10 years. And with new therapies like enzalutamide, like abiraterone, that are extremely effective, we're seeing this fracture rate actually going up. And so it's extremely important to think of bone health and to try to not treat everybody, but try to identify patients at most risk of having fractures and intervene. And the situation compounds itself if patients have metastatic disease because now we're combining the bone loss from ADT and the metastatic burden that causes bone fragility, fractures and what we call skeletal complications that can be catastrophic for patients.

And so hopefully that message is getting out. It's been over 20 years we've been talking about this and unfortunately some people still don't take it seriously.

Alicia Morgans: So thank you so much. And I am hopeful that your conversation and you're raising awareness will help all of us really keep this top of mind because fractures can certainly limit mobility, but they also increase mortality and really can severely limit an individual's ability to be independent. And I think of all of this as sort of a frailty type phenotype and that can come from of course bone health issues, but also from loss of muscle mass, sarcopenia. Dr. Beer, I know you do a lot of work in this area, not only how to identify these patients who are becoming more frail, but also how to prevent or reverse that complication.

Can you tell us a little bit about it, how you think about it in practice?

Tomasz Beer: Sure. So I think in men with prostate cancer, we are dealing at the intersection of aging and hormonal changes, which can lead to loss of muscle mass, weight gain in the form of fat, diminished activity and of course, other side effects. And we're fortunate to have Dr. Kerri Winters-Stone at our cancer center, one of our leaders who's been leading a number of research projects designed to define the optimal exercise programs for prostate cancer. But as we learn more about exactly what the exercise prescription should be, the basic rule of thumb is that I think all men on hormonal therapy to the extent that it's physically safe for them should be participating in regular exercise that includes both cardiovascular exercise, as well as weight training, strength training.

And those have been shown to improve strength, improve mobility, reduce weight gain, and there's some suggestion they may help with bone health. There's some suggestion that they may also help with depression and activity levels. So when I talk to patients about starting hormonal therapy, we really talk about exercise as a regular part of their treatment prescription.

Alicia Morgans: I think that's phenomenal. And especially with the resources that you have with Dr. Winters-Stone, who is really a pioneer in this particular area, and we'll have to talk more about how we can help meet patients where they are in terms of that exercise prescription. Because I think that ensuring that patients are given an achievable goal and then achieving and continuing that process is so important and we don't want to under or over prescribe exercise. We want to find the right fit for the patient. So we'll get back to that in a minute. And part of all of this as we said, and actually as Dr. Beer mentioned, is mental health.

And that can include things like depression, cognitive change, which we know are associated at least to some degree with exposure to androgen deprivation therapy. So how do you think about those particular problems, especially since they can be so complex in society?

Charles Ryan: Sure. First, I want to thank the APCCC for putting the topic of mental health on the agenda. I am not a mental health expert, but I think that any of us who face patients with prostate cancer understand that much as the patient has that confluence of androgen deprivation, aging, etc., men in particular who are at risk for major depressive disorder compared to women, for example, who are then faced with a cancer diagnosis, who are then faced with a hormonal depleting therapy are at multi-time augmented risk for depression. And I think we need to raise the awareness of this in our clinical time that we spend with patients in our clinics.

We need to know how to screen for depression, and we need to know how to route a patient or guide a patient if they are experiencing depression. And so the efforts that I'm trying to get across in my talk here at APCCC and I think as far as an overall survivorship strategy is that we're not going to know about the mental health of our patients if we don't ask, and so we need to be empowered with the tools to do that. And we are facing a very at risk population. Many of our patients could improve their quality of life enormously by addressing an undertreated or an untreated depressive disorder.

And everything you're saying about bone health and cardiovascular health applies to mental health as well to a large degree. Exercise, etc., all is very, very helpful, but it's not enough in many cases in many patients. And so they need to get the guidance from mental health professionals. And that's going to start with us because we are seeing them in the clinic as the gatekeeper and we need to help them get the resources that they need.

Alicia Morgans: Absolutely. And there are treatments for depression just like there are treatments that we've just alluded to for all of these issues. And I think depression of all of them can be one of the more complex to discuss because there are sometimes concerns that people have just from societal concerns, and I don't need that, that's not me. How do you deal with that?

Charles Ryan: Well, I would also just point out that there are treatments for depression. But when we think about this patient population and what we are doing for our patients hormonally, etc., one wonders if there's a particular type of depression or flavor to the depression that can occur in a man on androgen deprivation therapy. And there's surprisingly little literature on the use of antidepressants and psychiatric care in general for men on ADT. So that's how I'm thinking about it is thinking not only personally and what I'm lecturing about here APCCC, but also what we're thinking about in the overall survival context with what we do in the Prostate Cancer Foundation.

This is something that I think is an underappreciated area. It's a wholistic part of everything we're talking about, exercise and treating the whole patient as the whole self. But there's still so much to learn and I was really quite surprised at the lack of definitive data on treatment of depression in androgen deprived patients.

Alicia Morgans: Absolutely. Well, one area where there's actually a fair amount of data, but under utilization of it is the bone health data and that bone health area. So I wonder, Dr. Saad, if you had to give a message to patients, to clinicians on that particular topic, what would that message be?

Fred Saad: Well, it's very much like everything else we're talking about. I mean, we have to be aware first. You have to be aware that there are issues in terms of muscle strength. You have to be aware that these patients are at risk and you have to be aware because patients don't look like they're sick when we start them on therapy. And if you don't ask, they're not going to tell. And so being aware and considering the risk of the patient. So, what we do in the clinic is first, make them aware that this is going to happen. It's undeniable that it's going to happen.

And then we have to identify the risk, the age of the patient, patient history. And we've got tools that are easy to use. Within a few seconds, we can figure out whether the patient is at low risk, moderate, or high risk. Calcium and vitamin D is a minimum. Exercise is extremely important for bone health and muscle strength and for depression for us. And then in patients at moderate or high risk, these patients need a bisphosphonate or a RANK ligand inhibitor like denosumab. And if they're non-metastatic, once a year, bisphosphonate intravenous daily, or denosumab every six months at a very low dose.

If they're metastatic, castration-resistant, that's a whole other ballgame. These patients really need intensive therapy. And we saw that in two studies, one that didn't insist on using bone protective agent and the fracture rate was astronomical. It actually probably led to an increase in mortality, as you said. And in another study where before you force patients to have bone protective agents, the rate of fracture within a year was over 30%. And this is even in patients that didn't get radium, just enzalutamide alone in ADT in these MCRPC patients.

And that plummets down to under 3% just by using a bone protective agent. And so I think the data is there. It's very solid. We just have to be aware and personalize the care for our patients.

Alicia Morgans: I agree. And also talk about it, like you said, to raise awareness is so critical and to remind us while we're in these busy clinic visits that these are issues that are real for our patients. It's not just their PSA or their measurable disease. It's the rest of them too. And Dr. Beer, as I mentioned, you have such an opportunity to work with a team that is so focused on this and is doing research and clinical support in the prevention of physical frailty and maintenance of physical strength and balance and all of it. What would your recommendation or guidance be to programs that may be in smaller private community practices or other places?

What are the key things that they can do now without having a Dr. Winters-Stone?

Tomasz Beer: Sure. So I think some of the things that we found in our research, which may not be immediately translatable into every community, but I think are of interest for folks to know is that exercise aimed at cancer survivors in dedicated groups is a wonderfully successful approach. We found that folks that participate in those form social bonds with like-minded individuals. And these groups, it's been just remarkable to see how enduring they are. And the most recent research from the group has shown the power of couples exercise where both the cancer survivor and their spouse or partner come together serve as mutual coaches.

And we have preliminary data that shows that actually strengthens the relationship in addition to the physical health. But in an environment where such programs are not available, one can do 90% of that. I think for my patients who don't have access to those groups, I would suggest first starting with their physician to make sure exercise is safe and perhaps a one time assessment by a physical therapist or a qualified trainer to design a program. And for most patients, what we're talking about is a three times a week program that includes about a half hour of cardio and a half hour of weight training.

That's kind of the base minimum. The weight training seems to be a surprise for most of the folks I talk about. Everyone thinks about jogging or treadmill, but we actually do need to lift weights to maintain strength as we age, even when we're not on hormonal therapy. But certainly when we're on hormonal therapy and muscle loss is a big feature of that.

Alicia Morgans: Thank you for that guidance and advice. Because like you said, I think weight training is underappreciated, maybe because we focus on that aerobic activity so much but it's so critical. And any recommendations or guidance, what would that be from a depression standpoint?

Charles Ryan: So my recommendation is that if you're a clinician taking care of men with prostate cancer, you at least know how to screen for depression. It's pretty simple. There are a couple of guidelines that you can look up that can do it. It starts with somebody who's in a depressed mood several days per week, and then there are other associated symptoms that come up, sleep disturbance, etc. And I think that what I would suggest is clinicians know that this exists, it's obvious that it exists, but know to ask about it and then know your resources locally to get help for patients who need, whether it's pharmacological help or counseling or other things.

We lose patients to suicide who have cancer. A cancer diagnosis is a risk for suicide. We are doing tremendously dramatic physiological interventions to our patients with regards to their mental health, and we need to be aware of that.

Alicia Morgans: Thank you. Well, I appreciate all of you really coming together on this big topic, because I think that our patients need it and our clinicians appreciate it. So thank you so much for your time and your expertise today.

Tomasz Beer: Thank you.