Considerations of Bone Health in Men Treated for Prostate Cancer Discussion - Michael Cookson, Alicia Morgans & Fred Saad
November 8, 2020
Discussion: Considerations of Bone Health in Men Treated for Prostate Cancer - 20 minutes
Independent Medical Education Initiative Supported by Myovant Sciences
Fred Saad, MD, FRCS, Professor and Chief of Urology, Director of GU Oncology, Raymond Garneau Chair in Prostate Cancer, University of Montreal Hospital Centre (CHUM), Director, Prostate Cancer Research, Institut du cancer de Montréal/CRCHUM
Michael Cookson, MD, MMHC, Professor, and Chairman, Department of Urology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
Alicia Morgans, MD, MPH Associate Professor of Medicine in the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.
Michael Cookson: Hi, I'm Dr. Michael Cookson at the University of Oklahoma and a professor and chair at the Stephenson Cancer Center. It's my pleasure to talk to you today about bone health. And that was an excellent presentation by Professor Saad. One question I had for you, and I think I saw it in your risk-adapted approach, but for the average urologist treating men on ADT, in those men who don't have bone metastases, what is your recommendation for monitoring their bone health? How often should they do a DEXA scan, a FRAX score? How should that be incorporated into the routine practice?
Fred Saad: That's a great question, Mike. So I think we need to estimate risk before we even start ADT in the ideal world. How do we estimate risks? Ideally, if patients get a BMD, that helps a lot. But there are some patients that are elderly that have other risk factors that we don't even [inaudible] and introduce therapies to reduce that risk and then follow them as they go along. And so BMD is really important when patients are at some form of gray zone and we want to make sure, do we need to do additional therapy or can we just recommend the basics? And so, I think that is, for the average urologists or radiation oncologists who are starting ADT, I think it's important.
If we can get access to BMD, obviously that helps to refine. And once they are, if we decide they are at low risk or intermediate risk and we don't treat, then they need to get a repeat BMD within about a year to see, because once they start the ADT, the first year is the most critical, is where there is the most amount of bone loss, so this is where you actually can help to determine if they need therapy. If you are going to treat because they are at high risk, then you can just repeat it two years later and make sure that these patients are being helped by their treatment. And also to make sure that they are taking their treatment, which is not something insignificant.
Michael Cookson: In your experience, do you see the preservation of their bone mineral density, or do you expect to see a decline as you go through treatment, even if they follow your prescribed plan?
Fred Saad: With low BMDs, when they are elderly, even before starting ADT. And it's amazing how many patients are actually walking around with osteoporosis. And if you talk to the osteoporosis expert, just being over 65 is a risk factor. But I think men are undertreated, and this is, I guess, a kind of gatekeepers opportunity to screen men that are walking around, smokers, and family history. And we pick up osteoporosis even before we start ADT. These are men that don't recognize, a bit like heart disease, where we've established criteria to try to pick up heart disease before their first heart attack, which is the ideal situation.
Michael Cookson: Exactly. So I find that too, men's health comes right into the intersection of the treatment for their advanced cancer. And so, we have a responsibility and a role there.
Fred Saad: We can't just think of their cancer and imagine that nothing else counts. I think we have an opportunity when we see these men to make a difference. And obviously, medical oncology is much more attuned to thinking of these things. But you and I are urologists and it's unfortunate, but sometimes we think too much about the PSA and the cancer and getting that PSA down, and sometimes we lose a bit of the big picture.
Michael Cookson: Exactly. Another question I have for you, on the patients with metastatic CRPC who have bone lesions, the two studies that you showed give some inference into the risk of fracture while treating their cancer. So in a patient not on a clinical trial, what would be your guidance for use of the AR targeted therapy when you're going to interject radium 223?
Fred Saad: Okay. So obviously if patients were well-managed in terms of bone health before reaching the state of castration resistance, that's great. But you saw from the studies, only 10% of these patients who reached the state of non-metastatic CRPC, which is years after starting ADT, only 10% are on bone-targeted therapy. We have a problem recognizing the importance. So if they weren't treated and they are non-metastatic CRPC or even metastatic CRPC, I think we have to try to figure out their risk.
So if they are metastatic CRPC, these patients need to get bone-targeted therapy. And at the higher dose, because these are really high-risk patients for significant skeletal events. If they are non-metastatic, then these patients, we have to figure out, are they at risk of osteoporotic fractures? So there is no indication at the high dose, but at least in the osteoporosis fracture prevention doses, those have to be considered. And obviously, if they develop metastatic disease over time in the bone, then that dosing has to go up to the level of trying to protect their bones from the complications of metastatic CRPC, where they go into a really high-risk category.
Michael Cookson: So would you feel comfortable treating them or continuing their AR targeted therapy if their bone health was in order while they are undergoing the radium? Or should they withhold that?
Fred Saad: So if they are on radium, they absolutely need to be on a bone-targeted therapy. That is now a strong, very strong recommendation that anybody on radium should be on a bone-targeted therapy because of the risks of complications. For the other AR targeted therapies, then I would just continue monitoring them like I would for anybody on ADT alone.
Michael Cookson: Okay.
Alicia Morgans: Wonderful. So Dr. Saad, I just have a couple of questions so we can kind of round out our understanding of these bone health agents as we start to wind down. We all want to make sure that we are doing the best for our patients, but we also have to recognize that part of that is understanding the complications. And one of the things that I have seen when I see patients who are treated elsewhere and then come into our clinic, is that sometimes medical oncologists, in their enthusiasm, to use bone health agents actually use the dosing that we would reserve for metastatic CRPC in the hormone-sensitive setting, whether that's metastatic or non-metastatic, more commonly in the metastatic setting. Can you just reiterate why it's important to stick with, really, what the guidance is because that is what is studied? And maybe talk a little bit about the complications that come when you use these agents for a prolonged period of time or the risk of those complications.
Fred Saad: Okay. So that's a really important part, Alicia. So obviously the risks of complications are really linked to the time of exposure. So at the high dose, beyond two years, we start to get into more of a higher risk of the main complication that we are worried about, the osteonecrosis of the jaw. So by simple measures of preventing, getting them to go and see a dentist before starting, and making sure that if they need any dental work, to get it done. But obviously, even if you do all of that, if you expose patients for five or six years, the risk becomes a little bit exponential. So this is really the basis of why it is important to limit the high doses to the mCRPC patient, where those are the patients at the highest risk of complications.
Outside of the mCRPC setting, whether they are metastatic hormone-sensitive or castration-resistant that are non-metastatic, we're talking about the osteoporosis doses. For denosumab, that is one 12th, the dose we would be using. For zoledronic acid, it would be once a year, rather than once every four weeks. So really, we are not talking about the same. And in those levels, we very rarely, if ever, will see osteonecrosis of the jaw. So as long as they are not metastatic CRPC, we need to restrict.
And this goes with the level one evidence. All the trials showing efficacy were based on mCRPC. Even though it's very tempting to use it in the metastatic hormone-sensitive. If those patients respond well to therapy, they are going to live way beyond five years and you don't want to be exposing these patients to five years of intense therapy. So I think we need to follow the guidelines. But, more importantly, we need to follow the levels of evidence that the trials help us to understand.
Alicia Morgans: Great, thanks. And one final question I've heard from patients, "do I need to keep taking my calcium and vitamin D while I'm taking these? Aren't they supposed to work?" What is your comment on that?
Fred Saad: It's even more important to take the calcium and vitamin D if you are on these therapies because these therapies are rebuilding the bone. And how do you rebuild bone? You need calcium and vitamin D. So the risk is, if you're not taking adequate calcium and vitamin D, and not making sure they are not vitamin D or calcium deficient even before starting, is that you can get into problems of hypercalcemia, which almost never occurs if patients are adequately supplemented, and also check before you even start it.
Alicia Morgans: Absolutely. I just tell my patients, "These are the bricks and the mortar. If you don't have them, you can't actually rebuild that bone. Your levels will go down." So thank you for clarifying that and for sharing that with all the clinicians, who I'm sure after this re going to use a lot more attentive measures to make sure that bone health is really optimized for our patients, whether they are metastatic or nonmetastatic, castration-resistant or not. So thank you for your time today, Dr. Saad, Dr. Cookson. We'll wrap this up.
Fred Saad: Thanks a lot.