Darryl Mitteldorf – Executive Director, Malecare Cancer Support
Dr. Neal Shore – Medical Director, Carolina Urologic Research Center and has a practice with the Atlantic Urology Clinics in Myrtle Beach, South Carolina
Joel Nowak – Social Worker and Director, Advocacy and Advanced Stage Prostate Cancer for Malecare Cancer Support
Darryl Hi, everyone. This is Darryl Mitteldorf. I’m Executive Director of Malecare Cancer Support. Tonight we’ll be doing a teleconference that you’re all going to be listening to about bone health and prostate cancer, specifically around the advanced stage realm of prostate cancer. I’ll briefly introduce our organization and then our speakers and then we’ll get on with the show. I’m happy to report there are about, right at this moment there are 948 people on line, so with any luck we’ll top out at 1,000, which will be quite nice, and I hope you all benefit from this.
Malecare, we were founded in 1998, and we’re America’s largest prostate cancer support and patient advocacy non-profit organization. We’re also America’s only men’s cancer survivor support and advocacy organization. We’re a founding member of the Global Prostate Cancer Alliance and a leader in advocacy for underserved populations, such as gay men with prostate cancer and African-American men with prostate cancer. More information about Malecare services can be found at www.malecare.org. We also fund research through our cancer research funding platform called Start a Cure, which you can find at startacure.org, and startacure.com as well. And one of our speakers runs an extraordinarily informative website called advancedprostatecancer.net, which I invite you all to go to.
Tonight we’re honored to have Dr. Neal Shore as a speaker. Dr. Shore serves as Medical Director for the Carolina Urologic Research Center. Dr. Shore has conducted more than 250 clinical trials focusing mainly on prostate and bladder disease, and serves on the boards of several academic and advocacy networks.
Joel Nowak, our other speaker, is a Social Worker and Director of Advocacy and Advanced Stage Prostate Cancer for Malecare Cancer Support. He is a member of a number of committees and board of directors for various prostate cancer organizations.
Gentlemen, please continue the conversation.
Joel Good evening, Dr. Shore. This is Joel Nowak, by the way. I’d like to say it’s really a great pleasure again to have the opportunity to speak with you about prostate cancer, with the goal of educating survivors about how to live longer with a better quality of life. I would like to remind our listeners that anything they hear this evening is meant to provide them with thoughtful questions that they may take back to their own treating physicians. Also, I want to remind you that Dr. Shore does see patients, so I’m going to first ask that he provide you with his contact information, if he’s so inclined, so that if you wish to see him you could arrange that.
Dr. Shore, welcome. Before we actually jump into the topic of bone health, I’m wondering if you would like to share your contact information.
Dr. Shore Well, thank you. I’d be happy to. Before doing that, I’m honored to speak to the audience tonight on behalf of Malecare. I want to thank Joel and Darryl, you guys are doing just a tremendous job. Advocacy for men with prostate cancer, thanks to an organization like Malecare, has not only improved funding for the research that’s given us these great new advances in prostate cancer and improving patient survival, and at the same time therapies that are so better tolerated, but also creating a role in terms of our legislative awareness and the importance of men and the family, so getting the right screening, the appropriate testing, the appropriate therapies, and the right research. So, my hat is off to you guys. You do a great job. It’s a great organization and I’m proud to be here to speak with you.
My contact, I’m in Myrtle Beach, South Carolina, I’ve been there for over 20 years. I did my training at Duke for college and med school. Don’t hold that against me, since we lost in the first round of the NCAA. And I went and did my residency and additional training at Cornell New York Hospital and Sloan-Kettering. But for those who want to reach me, I’m the Director of Carolina Urologic Research Center, it’s www.carolinaurologicresearchcenter.com, and our address, our phone numbers, it’s all in there. Our main phone number in the clinic would be 843-449-1010. And anything we can do to help the listening audience with referrals or access or concerns regarding research studies, we would be happy to do so.
Joel Terrific, thank you. So we’re going to talk about bone health today, and I guess probably a good place to start, if you could please explain to us what is bone health.
Dr. Shore Well, that’s a great question. Women are such better advocates for so many of their health issues. Most women are fully aware of the concept and the definition of bone health and osteoporosis. And I had the good fortune of giving a plenary presentation just two years ago at the American Urologic Association on one of the challenges of bone health, identifying the issues surrounding bone health, specifically for our men with prostate cancer who get put on androgen suppressive therapies, but the National Institute Health Consensus definition of osteoporosis or worsening bone health is “Any skeletal disorder characterized by a compromised bone strength which predisposes the patient, male or female, to an increased risk of a fracture.”
So what’s bone strength? Bone strength, or bone health, is really equivalent to a combination or the two factors of bone density and bone quality. We’re able to measure bone density with what we call dexa scans. Bone quality, we don’t have very well described instruments, but we have family history and we have risk factors to better understand aspects of quality.
But when we have weakening or a demineralization of the bone density which leads to poor bone quality, this results in what’s known as either osteopenia, or really at its worst osteoporosis. And this is where women are much more intuitive about osteoporosis, because most women recognize once they go through menopause, postmenopausal osteoporosis, the acronym PMO, they’re at much higher risk for bone fracture. And yet there’s a real significant risk for male osteoporosis as we advance with age. Over the age of 30 we lose 1% per year of our bone mineral density. Men who undergo androgen suppressive therapies, whether it be with injections or surgical therapy, are at a dramatically increased risk for developing osteoporosis. So, having or being instituted upon any testosterone lowering therapy, for good cause, of course, for appropriate cause to combat prostate cancer, creates a significant risk factor.
Other significant risk factors for worsening bone health, i.e. creating the risk for osteoporosis which results in a marked increase for a fracture, and I’ll talk a little bit more of those fractures in a second, but other big risk factors are excessive alcohol use, chronic use of immunosuppressive therapies, for example, chronic use of steroids, are also a big risk factor. Other big risk factors is a sedentary lifestyle, not exercising on a regular basis, spending all one’s time watching TV and surfing the net, and not getting out and doing any type of aerobic activity.
And then the other thing would be family history. If you have a family history of a mother or father, a first degree relative that have a significant risk or have sustained fracture, you’re probably at an increased risk too. Diabetes, particularly significant diabetes, is also a risk factor, excessive smoking is a risk factor. So, these are all things that can be either recognized, and oftentimes proactively guarded against.
Joel Right, so obviously we have a couple of issues here as men with prostate cancer. Obviously, we’re getting older, which, as you’ve indicated, creates a problem for bone density. And in most cases, or many cases, we’re on certain treatments which encourage, or even advance the process, so, we’re at very high risk. Now, you mentioned measuring bone density, one of the measures you mentioned was a dexa scan, I think. Is that correct?
Dr. Shore Yes.
Joel Could you tell us a little bit about that? First of all, are there other scans, or things men can do, to monitor their bone density, or their bone health? And could you also tell us what the process actually is and how it’s done?
Dr. Shore Well, there’s a few things. The dexa scan, or the bone densitometry scan, is a relatively inexpensive, low exposure to radiation test that gives the physician information, with various scale, of a patient’s risk for developing a fracture. It’s a painless, fairly quick test. There’s not much preparation on the part of the patient, really anything at all. And the density is evaluated through the scan. And there’s what’s called a T-score and a Z-score, and really what it does is it gives a scaled reference to the physician and the patient to let them know do they have normal bone density, or do they have outright high risk for fracture, that would be osteoporosis, or a middle zone known as osteopenia. So that’s one nice way to measure and consider.
There’s another thing that’s really easy to do, and I don’t think as many physicians do it as they should, and I would encourage you, the listening audience can virtually do it themselves, and it’s recommended by the World Health Organization and by the National Osteoporosis Foundation, their websites are both excellent, particularly the National Osteoporosis Foundation website, where you can go and look up what’s called the FRAX, F-R-A-X Index. And it’s a very nice questionnaire. It’s really simply 12 questions assessing one’s risk for fracture, and it’s not only country specific, it’s age specific and phenotype specific. So, they’ll ask you your age, your sex, your weight, your height, prior fracture, history of smoking, glucocorticoids, and whether you have secondary osteoporosis.
Now, what we do in the prostate cancer world is if you’re on a testosterone lowering agent we consider you have secondary osteoporosis, so we check that off as “yes,” and also there’s a question on your alcohol consumption. And then what is also included is your dexa scan result. Twelve simple questions, pretty quick to put in the data, and then it creates a risk for you, a risk tolerance or a risk assessment, and whether or not you should then be recommended to be on an interventional therapy. Regardless of the FRAX score, virtually everybody should be on a really well balanced diet as we age. And there’s some controversy about supplemental calcium and vitamin D, but for our patients who are on therapies that are lowering their testosterone, what it does is it dramatically not only lowers their testosterone, but it also lowers their female hormone of estrogen, putting us in that same high risk category that postmenopausal women are. And it’s the estrogen that we start to lose dramatically too, in addition to the testosterone, that creates the poor bone health quality and the decrease in bone density. So, virtually all treatment algorithms recommend supplemental vitamin D and calcium to patients who are on any type of testosterone lowering agent.
Joel Terrific, good. Now, I know a lot of men confuse the dexa scan with a bone scan. They’re not the same thing.
Dr. Shore Correct, absolutely. They’re totally different. The dexa scan, also known as a bone densitometry scan test, strictly measures the density of the bone. It does not detect cancerous lesions, or metastases, as we sometimes call them. It is not a test to measure whether there’s been spread of cancerous lesions from any form of cancer, inclusive of prostate cancer. The bone scan test that we typically, traditionally order is called the technetium bone scan, and that’s a test that’s designed to measure abnormalities in the bone that could be consistent with cancerous spread, sometimes it can be false positive and show an old trauma, or arthritis, or a bone cyst.
Other tests that your physicians may order to look for spread of cancerous lesions are known as PET scans. Probably the most common one right now is what’s called the Sodium Fluoride PET scan, which is just another form of scanning to look for lesions in the bone. Neither the technetium bone scan nor the Sodium Fluoride PET scan has any type of measurement for bone density. And here’s another kind of important thing, once you have disease in the bones, if your cancer has spread to your bones then the dexa scan, the bone densitometry test, is no longer valid. It’s only valid in terms of an accurate measure of density when there are no cancerous lesions in the bone.
Joel Interesting. So, for a man who does not have any lesions, they still should be having a dexa scan, so, how often for a man who’s on hormone deprivation therapy should they actually have this scan?
Dr. Shore Well, you know, that’s a really good question. And there’s a little bit of controversy to it, but others and myself have looked at this and if a man is over the age of 70 and he has been diagnosed with prostate cancer, he’s already at significant risk for having osteoporosis. And then there are men who are under the age of 70 who have other risk factors that would put them at high risk for having bone loss and fracture. And that could be because of being on androgen deprivation therapy, that could be because of their alcohol or steroid history, their sedentary lifestyle, cigarette, tobacco abuse, all of those may put them at dramatic increase; men over 70, absolutely. Actually, it’s real interesting data that newly diagnosed men with prostate cancer, before they get any treatment, for unclear reasons, are at increased risk for decreased bone mineral density. We’re not exactly sure why. But once the diagnosis is made, we look at those risk factors.
Then what I typically do is we do the FRAX score, it costs nothing, it’s simple, it’s been very nicely validated to show an increased risk for fracture, we recommend lifestyle modifications, active lifestyle, get out there, supplemental vitamin D and calcium, get the dexa scan. If they have a T-score that puts them at risk, we start them on therapy, and we also look at their T-score in combination with their FRAX score.
Joel I see. Now, is there a relationship between loss of bone density and the development of bone metastases for men with prostate cancer?
Dr. Shore It’s never been that highly correlated. Honestly, the biggest risk of low bone density is a dramatic increase in fracture. Now, we’re talking about significant fracture, so when a man gets a hip fracture because he trips over some loose carpet in the house or some packages in a shopping mall, there’s a 30% higher mortality associated with that for men than for women. So, it can be a life ending event because of the complications associated with it. Other fractures and risks include lumbar spinal fractures and their associated back pain and requirement for surgical intervention.
So, there is no known association right now that we can really speak of between low mineral bone mineral density and the likelihood for developing a metastases, but one can have prostate cancer and get treated, get low bone mineral density, poor quality bone, suffer a fracture and the associated complications of that, and it can become a life ending event prior to the cancer coming into play.
Joel That’s pretty significant. I was not aware of that. Now, we’ve already discussed that treatments like ADT or hormone deprivation therapy can lower bone density. What about some of the other treatments men with prostate cancer have, radiation, chemotherapy, even the pain medications that we may take, will that have an effect on our bone density?
Dr. Shore You’re absolutely right. Chemotherapy, steroids, any of the other novel and new oral androgen deprivation therapies, all of these can have further potential negative impact on our bone mineral density, and of course radiation therapy as well in addition to our natural aging process.
So, I love the fact that you’re tackling this, because historically my specialty, and many others, we didn’t pay enough attention to this until the data has become overwhelmingly clear, it’s been well published in the New England Journal and in other organizations, and third party payors now recognize, not just Medicare but all the big insurance agencies out there, that preventative care to avoid these complications of these fractures is not only life saving in preventing of morbidities, but there’s a huge cost savings to it as well.
Joel Men with prostate cancer, what bones are more likely to be affected, where do they need to be careful, and so forth?
Dr. Shore Well, the fractures and the impact, we mostly see it in the lumbar sacral spine. We can see in what’s called a Colles’ fracture, one can fall, stick their hand out, and fracture their radius, that’s the classic areas that we look at, the lower forearm bones, the entire axial spine, as well as the hips. But suffice it to say, when one develops a lack of bone density or worsening bone density, worsening bone quality, there’s really no site of the entire skeleton that is spared, perhaps with the exception of the skull.
Joel Right. Now, one of the problems that I think many have, I certainly have shared it, is sometimes I wake up and something hurts, what I think is a bone, and more often than not it’s not a problem. So, at what point should a man decide that a pain, or an uncomfortableness, is worth calling their doctor about?
Dr. Shore That’s a great question. Look, I mean, most of us, myself included, when you get past the age of 40 we wake up with some sort of back achiness, unless you’re a devotee of Pilates or yoga, which I’m not but would strongly recommend. I think stretching and strengthening exercises are absolutely integral to good quality life longevity, regardless of the diagnosis of cancer. But your question is a very good one. We have various sundry pains, and part of it is one’s judgment, but I think also part of it is new onset of pain that persists in the setting of a known history of having a cancer, I think it is absolutely essential that one discusses that with their physician. One needs to use good judgment in terms of avoiding over testing, but at the same time having that judgment to recognize could this potentially be a new lesion, could this potentially be the first onset of a spread of disease.
And the really wonderful thing right now is we have so many great therapies to proactively treat the potential spread of the disease. We’d like to avoid it in its entirety, but when it happens, in the last few years we’ve had virtually six new approved therapies in advanced prostate cancer, so we want to make sure to at least have the discussion and to be able to avail both patient and physician to that therapeutic opportunity.
Joel Right. Now, obviously as the disease progresses and we get older we’re going to have to start dealing with some sort of bone problems, I kind of break it up into two categories, what I would refer to as the non-medical way and the medical way. And I don’t know if you …, but you’ve kind of touched on some of the non-medical ways, talking about drinking, talking about some supplements, so from a non-medical standpoint something that any of us could do without having to consult with our doctor that wouldn’t put us at risk, if you would review what you would recommend, what you’d like to see your patients do.
Dr. Shore I’m a huge proponent of any type of core strengthening exercise, whether you do meditation and yoga, and Pilates, or swimming, or a treadmill, or any sort of exercise tape, or brisk walking around your block, but getting out there, and movement and regular stretching and strengthening. One can get on to any website and just Google “stretching and strengthening core exercises,” and pick what’s good for you.
Our bodies are like the chassis of a car, you know, if we don’t maintain it then it will eventually break down and we lose our car more quickly. With the natural aging process, with a cancer or not, with additional therapies which can affect your bone density or not, or drugs that might affect your immune system or not, we’re aging, and we’re all effectively breaking down. I’m a huge proponent of making sure we try and prevent that as much as possible by a regular regimen of exercise. And it can be whatever it is that you are comfortable doing, 30 to 45 minutes a day, that’s all one needs to do, literally. It’s good not just for the skeletal complications of aging and cancer related therapies, it’s also vitally important for maintaining good cardiovascular healthcare.
So, regular reaching exercise, and then maintaining the right body mass index, so not being excessively skinny, but certainly not being overweight, and one can just look at one’s height and age and calculate your body mass index. I tell my patients, people always talk about the “little old man,” the “little old woman,” they never talk about the big, obese, fat man or woman who lives a long time. Obesity, as well as undernourishment, are both two ends of the spectrum that impact our bone health and also impact our immune and cardiovascular system, so, it seems almost trite to say it, but a very well balanced diet.
And then the next question is: well, what’s a good, well balanced diet? And honestly, I think any heart healthy diet is a good cancer preventive diet, and it’s a very good cancer diet if diagnosed. So, avoidance of excessive carbohydrates, lots of natural, organic fruits and vegetables, balanced, and lean meats, that, and a combination of regular exercise, avoidance of tobacco products, and alcohol in moderation.
There’s really no other data out there suggesting that excessive supplemental vitamins is beneficial, a basic multivitamin is fine. With the exception, if your vitamin D and calcium levels are low, then those should be supplemented to avoid the risk of further bone demineralization and worsening bone health.
Joel How would one measure one’s vitamin D and calcium level?
Dr. Shore Simple blood test, inexpensive, your physician can get that any time.
Joel So, you don’t recommend generally supplementation of them without knowing where your levels are, would that be a correct assumption?
Dr. Shore That is my assumption. I like to know what one’s levels are, because then I can give further guidance on the milligram dosaging.
Joel Right. And are there any other supplements that you think may be appropriate for a man with prostate cancer to consider taking?
Dr. Shore Right now that’s really my mantra. Of course, we can always individualize when we get full levels of complete blood count, liver, kidney, electrolyte functions, but I would be the first one to recognize and acknowledge and say take this one or that one. And I know there’s folks listening here who, they’ve read various articles, or they’ve gone to various supplemental stores and they’re very comfortable with what they’re taking, you know, as a physician scientist I still like to say I have to see the data to show the prospective study that it really makes a difference. There may be some things out there we just don’t know about yet, but, again, I don’t like to advise my patients to take on therapies that I haven’t seen well designed studies showing the benefit; and B) avoiding them from a cost standpoint taking something.
And the other third part of it is, Joel, is that so many of these over-the-counter vitamins and herbal supplements and mineral supplements, there really is a tremendous lack of any quality standards and quality control. Now, I’m not saying it’s true for all of them. It may just be true for a small minority. But the fact is from a regulatory standpoint, because the products are over-the-counter one just needs to be very careful of who they’re buying them from to make sure that the purity is there.
Joel Right. Are there any specific supplements that you urge us not to even consider taking, forget the quality control issue, but do you think that could be deleterious to our cancer?
Dr. Shore Well, I don’t know that it would be necessarily deleterious. It might be more deleterious to one’s pocketbook. But saw palmetto was very popular for many years, I mean, I think it’s been clearly shown to have virtually zero value. I used to see many of my patients coming in wanting to take it. It’s a phytoestrogen extract, it may modulate PSA in some patients, but it’s absolutely never been shown to have any clinical benefit whatsoever. There were other things that were out years earlier, and it’s a real cautionary tale. So, my advice would be, it gets back to regular exercise, a balanced diet, avoidance of tobacco, alcohol in moderation, and then take the therapies that are A) approved; or B) a well reviewed and carefully monitored clinical trial.
Joel Terrific. And now I’d like to move into a conversation about some of the medical methods of dealing or treating bone mineral density issues and of course prostate cancer lesions in the bone. Could you talk a little bit about what options are available out there?
Dr. Shore For the treatment of bone mineral density issues, one can be started on regular exercise, like I said, vitamin D, calcium, and then one could theoretically, these are for just men and women in general, they can supplement with therapies known as bisphosphonates. And these are medications that can be given intravenously or orally which are designed to help stabilize bone loss in healthy patients. As it pertains to men with prostate cancer today there’s only one bisphosphonate approved, and that’s known as zoledronic acid, the trade name is called Zometa, and that’s given intravenously to men who have bona fide disease lesions in the bones to prevent further complications of those bone lesions, fracture, pain, the need for surgical intervention. So, zoledronic acid was the first and to date the only bisphosphonate approved for men who have spread of their cancerous lesions into the bone.
A few years ago another, and this is called an antiresorptive therapy, and what it does is it prevents these little Pac Men-like molecules called osteoclasts from further scavenging up the bone. Interestingly, the bone is a dynamic organ, we have what are called osteoblasts which build bone, and osteoclasts which resorb the bone, and our bone is constantly in a state of remodeling itself. When we develop lesions in the bone, that dynamic mechanism, or that homeostasis, that balance gets disrupted because of the cancerous lesions, and that’s where we get into an increased risk for developing fractures and pain associated with lesions in the bone.
The therapy that got approved a few years ago is an antibody, it’s not given intravenously like zoledronic acid, it’s given with an injection under the skin that’s known as giving it subcutaneously, and that’s called denosumab, and it blocks a receptor which slows down the scavenging effect of the osteoclasts. The trade name for denosumab is called Xgeva, and we give it to men who have cancerous lesions in the bone to prevent them from getting any complications from those lesions. That same drug, that same antibody, denosumab, at a lower dose is given twice a year to men, and to women, to prevent osteoporosis, whether it be related to aging or for men who are on any testosterone lowering therapy.
Joel How do you decide, since they both have somewhat the same bottom line, or end result, Zometa and the Xgeva, how do you decide which is the more appropriate drug for your individual patient?
Dr. Shore Yes, that’s a very good question. Both zoledronic acid (Zometa), denosumab (Xgeva) are approved for men who have advanced prostate cancer bony lesions, and the medicine’s given to prevent the complications of those bone lesions, which is what we call SREs, or skeletal related events. Zoledronic acid (Zometa) was approved first back in around 2004, and denosumab was approved in late 2010.
Zoledronic acid is given intravenously, Xgeva subcutaneously, so it’s a little easier to give it, you don’t have to put it in an IV, the Xgeva’s given just underneath the skin so it’s quicker and simpler. I like that. The zoledronic acid is cleared by the kidneys, so you always have to check the kidney function before giving it. The Xgeva is not. It’s a form of an immune therapy. It’s cleared by the immune system, not by the kidneys, so you don’t have to check kidney function each time, so I think that’s an advantage.
And then, quite honestly, we did a head-to-head trial, I’m one of the authors, we presented our findings in The Lancet and we published it there, we did an actual head-to-head study of men with advanced prostate cancer who had bone lesions, they either got Zometa versus Xgeva, and actually Xgeva was superior in terms of better delaying complications known as skeletal related events. And so I tend to be really an exclusive user of Xgeva. There are some who will use Zometa, I think there may be some cost advantage right now, but for my mind the Xgeva was superior in a head-to-head trial in delaying the complications that you’re trying to delay, it’s easier to administer, it’s subcutaneous versus intravenous, and there’s no risk for kidney impairment.
Joel My perception is that many more physicians prescribe Zometa, so it may well make sense for some of us listening in on the conversation to question their physician as to how that choice is being made, or why the choice is being made.
Dr. Shore Well, I don’t know that. I think that both are good and effective therapies. My impression in the prostate cancer world, but I’d have to look at that data, is I think really virtually all new starts would be getting Xgeva. But I’d have to see some fresh data. But, you know, honestly this was a trial known as the 103 Trial, we published it in The Lancet. For the listening audience, The Lancet is the European version, I think it’s fair to say the equivalent to the New England Journal of Medicine, so it was a fairly landmark publication. I was proud to be one of the authors on it. Again, zoledronic acid (Zometa) a good drug but I think in a head-to-head trial, we see so few of them, and this was a phase III multinational prospective blinded trial, Xgeva bested the results of Zometa.
Joel What about side effects of these two drugs?
Dr. Shore Well, you know, like everything there is the risk of side effects. Kidney dysfunction is a potential side effect of zoledronic acid; not at all really for Xgeva, also known as denosumab. Both of these therapies they can develop some very mild muscle ache type symptoms right after infusion. That’s not really been an issue. Both of these therapies can develop this rather unique complication known as ONJ, or osteonecrosis of the jaw. It sounds like a really horrible, weird name, osteonecrosis of the jaw, but in reality it occurs about somewhere a little over 1% per year in each of these therapies, and it’s primarily associated with, not so much dental surgery, but oral surgery, so, having a tooth extracted, or periodontal work, there’s poor healing at the gum line. So, all of my patients who are going to start on either zoledronic acid or denosumab, I always recommend that they see their dentist and if they’re intending any type of oral surgery they get that done way in advance.
Joel And if a man is already on these drugs and they need periodontic work, what do you recommend?
Dr. Shore Well, that’s a great question. There’s no easy answer to that. There’s no wrong answer. I think in my situation typically what I’ve done is I’ve withheld the medication. We don’t know that that makes perfect sense for some. It’s sort of a balance. It depends upon the severity of their disease. Oftentimes I’ll usually be more conservative and hold therapy, but I do have to individualize that to the patient.
Then the question becomes, how long can you hold the zoledronic acid, or the denosumab? For one thing, zoledronic acid, another potential small disadvantage is it stays in the system for years. Denosumab is usually cleared in about five half-lives, which is in about four to five months. So some of my patients I’ll tell them if they can hold off on their tooth extraction, get off of the denosumab for at least a four to five month period, and then have their oral surgery.
Joel Right, so there’s another question that comes up periodically, and that’s at what point a man should actually start therapy.
Dr. Shore Yes, I’m fairly aggressive in that. Of course, you know, one has to always individualize the patient, and that’s still the art of medicine and why it’s still such a privilege and joy to practice medicine, because there is the practice of medicine. What’s good for one patient might not be good for the same next door neighbor, despite the fact that they have advanced cancer with bone lesions. One needs to look into the volume of the bone disease, the lifestyle of the patient, any other co-morbidities or other health processes that they may have. But I tend to be fairly proactive in trying to start patients on therapy, because we have so many therapies out there right now.
One of my philosophies is I want to keep my patients with advanced prostate cancer going for absolutely as long as possible. And if they progress I want to make sure they haven’t progressed too far that I wasn’t able to offer them all of the approved agents at an appropriate and timely nature.
Joel At ASCO GU there was a paper, or actually a poster, that talked about some long term negative effects of therapy. Are you familiar with that, by any chance?
Dr. Shore Well, which –
Joel Well, there was a couple of them, but the one I’m thinking about is the other more serious femur fractures.
Dr. Shore Yes, there have been some data in long term use of intravenous bisphosphonate, primarily zoledronic acid, and some, what are called atypical femoral neck fractures. Fortunately, they’re a very small number, and it’s not really well understood what the pre-disposing factors are to that. It certainly is something that needs to be considered.
Both zoledronic acid is approved, in its label, to be given once every three weeks, denosumab once every four weeks, and what we don’t really know is, we don’t have adequate data to understand would patients do better, not necessarily better, maybe better in terms of less side effects, we don’t have this data, nor do we have data to know would they do equally well in terms of delaying complications by extending those three week and four week regimens, respectively. And so that data, we just don’t have that data. I would imagine that some patients and physicians, somewhat off-label, maybe extend the timing of the therapy in the hope of avoiding some of these small but potential complications.
Joel Right. And to move on a little bit, obviously when a man develops bone metastases which is the most significant … target of prostate cancer lesions, we have some treatment center now available for these men who are dealing with bone metastases. Perhaps you could talk a little bit about what is out there and where we’re going with that, if you don’t mind.
Dr. Shore Sure. Well, we just touched on the fact that men with advanced prostate cancer in the last few years have certainly had a discussion with their medical oncologists, urologists, radiation oncologists about the antiresorptive therapies of zoledronic acid (Zometa), denosumab (Xgeva), because these drugs prevent the development of those complications delaying the onset for pain and delaying the risk for fracture. We have focal radiation therapy to help with that pain and potentially reduce the risk of fracture as well.
But one of the biggest breakthroughs, specifically for bone lesions and bone related complications has now been the approval of radium-223, also now known commercially as Xofigo. And this is a radiopharmaceutical, or an isotope, it’s in the Periodic Table of Radium, and it’s given intravenously over about a 45 second timeline once every month for a period of six months. And the large phase III multinational trial that the FDA and the European Medical Authority have now approved, the FDA approved it last May 15, 2013, and it’s been commercially available since the summer, in fact, we were the first site in the entire country to give it at the end of May, post FDA approval, so I’m proud of that. It’s very easy to administer, it’s 45 seconds. There’s no pre-medication, there’s no post-medication to take. And the drug was approved because it’s the first and only, what’s known as a radiopharmaceutical to not only delay complications of bone lesions, but it’s the first and only radiopharmaceutical that has been shown to prolong life. And that’s a huge breakthrough. So, it’s received Medicare approval in all the Medicare carriers throughout the United States.
So it has a very unique mechanism of action, the way it works. It works strictly on bone lesions, where the bone mineralization is occurring from this imbalance between osteoblasts and osteoclasts because of the cancerous cells, and it’s very well tolerated. It’s not metabolized through the kidneys or the liver, like most drugs are, but rather just comes out in the gastrointestinal tract, so the only side effects that we saw in the study was a very low grade, low incidence of diarrhea. There’s no hair loss. There’s a very small, about 1% to 2% potential incidence for some suppression of the bone marrow.
The radiopharmaceuticals that were available prior to radium-223 that never showed an impact on improving patient survival but only helped ameliorate pain, which radium-223 does as well, were different kinds of radiopharmaceuticals, they were smaller molecules, and the nature of their small size put them at a much higher likelihood for causing suppression of the bone marrow, much like chemotherapies do. And when you get suppression of the bone marrow one has increased risk of complications, infection, risk for bleeding, anemia, etc. And we saw a remarkably low incidence of this with Xofigo, X-O-F-I-G-O, and so in addition to prolonging life, much like all the other great new therapies we have in advanced prostate cancer, very well tolerated, short infusion, and a unique mechanism of action.
Joel Right. Now, those other drugs, the earlier drugs you were talking about, strontium-89 and samarium, can one assume that they’re drugs that will go in history and there’s really no place for them any longer?
Dr. Shore Right, the strontium and samarium, because these are beta and gamma isotopes, radium is an alpha isotope, so they’re different types of isotopes, the alpha being larger it doesn’t penetrate deep into the bone marrow. In the United States I think it’s fair to say that with the accessibility of radium-223 I do think that the samarium and strontium will become relegated to history. But in other parts of the world where radium isn’t necessarily available, I think some folks will still have access to it and will use it for palliation of pain.
Joel Right. And what about the role of IMRT, or external beam radiation, to target some of these mets, and how does that interplay, if it’s a reasonable thing to do, how do you decide when that’s an appropriate treatment as opposed to the Xofigo?
Dr. Shore Yes, it’s a great question. It’s always important to have a collaborative and a multidisciplinary discussion, whether it’s your urologist, or medical oncologist, with your radiation oncologist, because it’s only radiation oncologists who are going to administer IMRT or external beam radiation therapy, spot radiation for the acute amelioration of pain, and it’s only either a radiation oncologist or a diagnostic or a nuclear medicine radiologist who can administer the Xofigo. It has to be somebody who has the appropriate licensure, so that’s very important. I’ve given now many patients Xofigo, and I’ve given many of them who have undergone a 10 day course of treatment with focal radiation to get acute amelioration of their pain, and then once they’ve concluded that, then I proceeded on to the Xofigo, because the Xofigo is administered over a six month period.
Joel And just to move on a little bit, use of pain medications, always a controversy, and obviously as metastases develop and grow they become very painful.
Dr. Shore Well, you’re right, and it’s very important that, and you just jogged my memory, the phase III trial that led to the approval of Xofigo and its label approved indication is for symptomatic bone metastases, symptomatic bone lesions in the setting of patients with advanced prostate cancer. And so by symptomatic, symptomatic can be somebody who might be on a narcotic analgesic, but it could also be somebody who’s on ibuprofen for cancer related bone pain, so, there is a nice flexibility. As long as the patient and physician feel that their bone lesions from cancer are causing symptomatic pain, then they are a potential candidate for Xofigo.
Joel Right. And can I assume that you would be supportive of bringing a pain specialist in at some point to help with palliative issues if necessary?
Dr. Shore Well, you know, that’s an interesting thought. In my clinic, in my area we don’t necessarily have a “bona fide” pain specialist. I think of myself, my radiation oncology colleagues, my medical oncology colleagues, some of my pain specialty colleagues who really mostly work on nerve blocks, I would occasionally consider bringing them in as well. My experience is that most pain specialists per se, they deal with the eradication of pain, but may not have a full understanding of the overall oncologic issues involved. But I don’t think there’s a problem bringing them in, especially when you have refractory pain. If you can give an injection and get amelioration of the pain, that certainly is not unreasonable.
Joel Right. Now, I’m going to push the envelope and ask you an out-of-the-box question. What about the use of estrogens to support bone health along with perhaps a hormone therapy?
Dr. Shore As I said earlier, and you’re absolutely right, estrogen is vitally important to bone density integrity. Most men don’t realize that we have estrogen levels, and women have testosterone levels. The ratio is normally obviously very different and it accounts for our muscle mass, hair patterns, etc. But when we go on, as we age we undergo these therapies and we get depleted of testosterone, we get depleted of estrogen and estradiol, it can dramatically affect our bone mineral health, our bone density, our sexual function, and thermal regulatory, hot flash issues as well. There have been studies, and there are people who do look at supplemental estrogen, transdermal estrogen, some low doses of estrogen to help with symptoms, and even to help with progression of prostate cancer itself. There are some good studies looking at that. They’re ongoing. But right now I think so much of it, quite honestly, is mostly investigational.
Joel Got it. Unfortunately, this is – not unfortunately, this has been really informative, but we’ve eaten up time and I have a bunch of questions that people had sent in. So, I’m going to just kind of cherry pick just a few of them, if I can still hold on to you for a little bit longer. Would that be okay?
Dr. Shore Sure.
Joel Okay, now Dan asks if Xofigo stopped the growth of bone lesions, or he said, “as my physicians tell me, just relieve pain and offer a statistical life extension?”
Dr. Shore That’s a great question. One of the challenges in the ALSYMPCA trial, which was the phase III trial, there wasn’t a regular follow up to look radiographically to get that data. I can tell you empirically and from talking to my colleagues, it’s certainly not all, but there’s definitely a number of patients where we’ve seen eradication of lesions and certainly stabilization of the lesions. But I would say that’s not the majority. But that data and further prospective looks at following up radiographic assessment is ongoing. But I can just tell you anecdotally that I have seen some very nice resolution of bone lesions, but not in all patients.
Joel Right. And Herb asked if you would comment on the potential role of strontium as citrate or ranelate in bone protection, both for osteoporosis and for metastases prevention treatment. And maybe you can explain a little bit what that is.
Dr. Shore Yes. So there’s no role for strontium for osteoporosis prevention or prophylaxis. There’s no role for strontium in prevention of developing metastatic disease. The only role for strontium is in amelioration of symptomatic bone pain. And it can’t be given concomitantly with chemotherapy, nor can Xofigo, for that matter either. But there are some studies that are now looking at giving chemo and Xofigo concomitantly, at the same time. That’s in study, but it’s not approved by label.
There’s only one study to date that has shown a therapy to delay the onset of metastases in patients with advanced prostate cancer, those with a rising PSA and a testosterone level that’s been suppressed, and that was a trial that was done by Amgen using denosumab, the Xgeva drug. And we did that study, and again, we published it in The Lancet, and I’m proud of that publication, it was a wonderful study, it was well over 1,000 patients and it showed a statistically significant improvement in delaying the onset of metastases. Unfortunately, the FDA did not approve it. They felt that the improvement of four months delay was not clinically significant and we had what’s called an ODAC, and unfortunately they did not vote for its approval. I think it was personally, from my standpoint, very unfortunate, because it is to date the only therapy that’s been shown to delay the onset of metastatic disease in a population who are starting to have a rising PSA despite a suppressed level of testosterone.
Joel Right. And Mary Sue asks an interesting question. Should people with node only prostate cancer also be concerned about their bone integrity? And what treatments, if any, would you recommend, or supplements, that may help them not progress on to bone metastases?
Dr. Shore That’s an important question. As I said, virtually everybody with newly diagnosed prostate cancer in and of themselves is at an increased risk for having decreased bone density; patients with nodal only disease certainly have advanced disease outside the prostate. If it was picked up by lymph node sampling and not by x-ray it’s microscopic disease as opposed to macroscopic, found in larger volume on CT scan presumably. I’m of the opinion that if you have significant nodal disease you almost invariably have microscopic disease, probably somewhere in your bone milieu, the bone environment. We just haven’t necessarily found it. We don’t have any approved agent right now to prevent the onset of developing bone metastases.
For patients with lymph node metastases who failed primary therapy, whether it’s surgery or radiation or some form of freezing or heating, the standard of care at some point is to just be started on an androgen suppressive lowering therapy. Recently there was that very interesting data that came out of a large study looking at patients who presented with advanced disease who actually were randomized to testosterone lowering therapy versus a testosterone lowering therapy in combination with chemotherapy. And that data has apparently been statistically significant, showing a prolongation of life, the ones who got chemotherapy who were started initially with androgen deprivation treatment, and that data will be presented at ASCO this year.
Joel Right. And I’m going to ask one more question, if I may. Rhonda, who is married to a 54-year-old man who is on intermittent hormone therapy, failed surgery, he is very active, goes to the gym every day, and unfortunately he had a fall and he broke his wrist bone and is in a cast. And he’s now not able to go to the gym. Are there things that he can do, supplements, you know, other things that he can do to help his wrist to heal more quickly and properly so that he can get back to the gym and do what you recommended?
Dr. Shore Yes, I would definitely want to know, if I were him, what my vitamin D and my calcium levels were. And just because I had a cast on my wrist, it wouldn’t prevent me from doing other forms of safe, aerobic exercise related activity. Please don’t fall and break the other wrist or your hip, but get out there and do something that’s safe, but continues to create a cardiovascular workout.
Another little simple thing is, especially for our older patients, is well fitting shoes, invest in good quality shoe care. Get rid of all loose rugs and carpets and tiny stools and chairs in the house, things that you could trip over, you know, slippery floors, get rid of slippery tile in the house, and dog bowls and children’s toys. All these little things, they seem trivial, but they can sometimes end up causing a fall from imbalance and these lead to these fractures, what we’re trying to avoid. But for the patient here, keep out there and keep staying busy, but just do it in a safe way.
Joel Terrific. Dr. Shore, I have to say that this has probably been one of the best teleconferences that we’ve had, and I really thank you for that. What you’ve shared with us I think is important and what makes it really good is that it really talks directly to us in our daily living, which is so vital and important. I look forward to perhaps trying to convince you to come back and talk about another topic. I think it would be really appreciated. So, thank you so much.
Dr. Shore Well, thank you, and thank you for all the great work that Malecare does. I really appreciate it.
Joel And again, you had a chance to meet Dr. Shore and if you are anywhere in the North Carolina area, I think you should feel free, if you so want, to call, make an appointment, and get a consult. Anyway, thank you, again, everyone, and remember, take care of your bones. Good night.