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Alicia Morgans: Hi, my name is Alicia Morgans and I'm a GU Medical Oncologist and Associate Professor of Medicine at Northwestern University. I'm so excited to have here with me today, a good friend and colleague, Nurse Practitioner, Brenda Martone, who is the nurse practitioner who sits next to me and tells me how to practice each day and is an incredible addition to our clinical practice. I wanted to talk with you today, Brenda, about how we think about choosing patients for treatment with radium because this is sort of a unique patient population and is a decision that really, I think we contemplate on a regular basis and engage patients in those conversations. So I would love to hear your thoughts on how you consider this particular therapeutic.

Brenda Martone: I'm happy to be here and looking forward to talking with you.

Alicia Morgans: Great, thank you. So, radium is approved in the metastatic castration-resistant prostate cancer setting, but as I mentioned, it is really a specific population that actually, in many cases, people consider potentially pretty narrow. But I think of it as actually a fairly broad population only limited by certain sites of disease spread, for example, or perhaps cytopenias. How do you think about when to use radium and who the right patient might be?

Brenda Martone: The patients we think about radium for are those patients who have bone-only metastatic prostate cancer. Radium is not indicated for those who have any soft tissues, such as lymph nodes or visceral disease. And we think about using radium based on prior treatments and where that patient is as well as how symptomatic that patient is. So radium is indicated for symptomatic metastatic prostate cancer to bone and oftentimes people assume or think that the symptoms have to be related to bone metastasis or bone pain, but that is not the entire picture basically. You could also consider people who are having loss of appetite, increased weight loss, worsening fatigue. Radium-223 is designed to help palliate symptoms. So we would consider that if patients are not only having bone pain but also if they are having these other symptoms and also the extension of prolonged overall survival is another thing to consider when talking about treatment options for patients.

Alicia Morgans: Yeah, I think that is a really important point because, as I was mentioning to you right before we started filming, I was talking with one of our fellows just yesterday about whether radium might be a reasonable option. This particular patient had bone-only metastatic disease, had some fatigue related to that disease, but didn't have specific intense bone pain. And we really discussed that fatigue is absolutely a symptom of the progression of his prostate cancer. And in this setting, particularly because we know that radium not only palliates symptoms but also prolongs survival, radium was actually the right choice for this patient who was, for multiple reasons, not interested in chemotherapy.

So I really think it is important for us to consider and recognize that symptomatic disease can be things other than bone pain specifically and I really appreciate that you have brought that up. And kind of to that point, sort of thinking back to my conversation with this fellow, in this particular patient, we chose to use radium in a patient who had not received chemotherapy, and the ALSYMPCA trial included patients who had had docetaxel previously, but also patients who were not fit for docetaxel or patients who opted to not be treated with chemotherapy.

How do you think about the timing of radium in terms of sequencing around chemotherapy when you are in your practice? Is this something that you think really should be after chemotherapy? Does it depend on how the disease is progressing? Does it depend on the patient's preference? What do you think?

Brenda Martone: I actually think all of those things kind of come into play when you are helping patients decide treatment options for them. Oftentimes, some patients just are not chemo fit and would be better off with the radium and getting some palliation of symptoms. Other patients just prefer to have a treatment that's targeted, more targeted, that gets taken up directly by the bone and has hopefully fewer toxicities or less toxicities in terms of chemo. So, for patients who are symptomatic, this would also be a really good treatment choice and chemotherapy could also be appropriate in this setting.

The other thing to think about is making sure the patient's bone marrow is strong because again, you have to watch blood counts, et cetera. So that may influence timing and treatment choices and opportunities. And again, because it is only recommended in bone-only disease, the past doesn't predict the future. So you certainly want to have multiple options and not have a treatment option fall off the list if they develop visceral disease. So in terms of also directing patients, you can think about, well, we have this opportunity right now, let's go ahead and take it. And again, just like any other treatment, if we find that it's not helpful or it's causing side effects that are not tolerable, we stop and then we reassess and move on to the next treatment.

Alicia Morgans: Yeah, I think that's a great point. Sometimes when patients especially are thinking about multiple treatment options and they have one option that's available now, but may not be available in the future, I similarly try to say, "Well, perhaps we should get this treatment under our belts now while we do have the decision-making capacity, while we can actually make that choice, because we may not have the opportunity to think about that in the future." So that's a really great point.

One of the things that's interesting and kind of unique to radium is that we have the opportunity as medical oncologists to partner with nuclear medicine physicians and teams to give this therapy. And I know you work hand-in-hand with the physicians and the technicians in the nuclear medicine department. Can you tell us a little bit about how you make that collaboration work so well and how you monitor patients in a way that doesn't get bothersome? Because we do need to have the CBC about a week before we give each dose. So how do you help make that really work?

Brenda Martone: Well, we have an excellent relationship with our nuclear medicine colleagues and from the very beginning, when this treatment was originally approved, all of us were at the table. And so we all kind of decided how we should do things to make things flow. So we have a dedicated nuclear medicine technician, so once we identify a patient that potentially could be eligible or wants to pursue radium, we immediately complete paperwork and reach directly out to this person, Munther, he is amazing and we let him know right away who it is, and then that person is on his radar. So as soon as he gets some paperwork back or approval back, he reaches out to us.

We then work on, together, how old the CBC is, can we use that, when do we need to get the lab repeated to get started? And then we identify treatment days and times, and then we circle back with the patients. Of course, they are always in the conversation and find out from them, when is the best day and time to come for treatment. And I think the process is really seamless because we all know who is doing what, and we understand the responsibility, as well as Munther, is outstanding also in the way that he keeps us on track. So he has his own patient tracker and he will let us know when it is getting close for somebody to come back for their next radium and just gently say, "A friendly reminder, we are going to need to get a CBC so that we can go ahead and assess and have the medication ordered," because it does need to be ordered and it is patient-specific and it takes some time to get delivered to the facility.

In terms of future treatments and planning, since the radium is given every four weeks, we like to see the patients back a week prior. So, basically, we are seeing them every four weeks, but it turns out to be that third week. So we're getting the CBC with differential as well as any other chemistries, doing our physical assessment to make sure that there are no side effects, the treatment is being well-tolerated, and we don't need to make any adjustments. There are times that we will get labs locally and the patient will come in the same day that they are getting their radium to see us first, and then we administer the radium in nuclear medicine. We're just really trying to make it as seamless as possible for patients because it does require multiple visits and it is to different departments so we want to just really make the experience for patients seamless and as easy as possible.

Alicia Morgans: Yeah, and thank you for pointing that out. One thing that I think is really special about the way that you collaborate is that yes, we need to see the patient every cycle, nuclear medicine needs to see the patient every cycle, and we need a CBC about a week before treatment. So whether the patient comes in to see medical oncology on the same day as the CBC, and then a week later comes back to nuclear medicine, or whether the patient gets a CBC at a local laboratory to have faxed into us and then sees us to determine whether they are really safe to pursue that dose on the same day as their treatment, it is something that can really be tailored to each patient and to his needs and travel restrictions or schedule. And I think that is so, so helpful and other permutations may be right for other practices, but our flexibility here, you are working so closely with the nuclear medicine team, I think has helped our patients. And as you said, they really keep us on track too.

So as we start to wrap up, I wanted to just touch on one thing that I know we both learned, certainly we've known from guidelines, but learned firsthand from ERA 223, which really demonstrated to us that bone health in the setting of treatment with radium is so important. And we know that bone health is important in metastatic castration-resistant prostate cancer, but this, I think, was a bit of a wake-up call for every practice. So wondering, how do you talk to patients about bone health? And is this something that you try to ensure that they are receiving before they start their radium or as they are starting?

Brenda Martone: Yes, being on xgeva, or denosumab, is so important. And so basically if patients are not already on this agent for CRPC, then we talk about why it's important to have it. We have them facilitate dental clearance, continue calcium and vitamin D, and I practice in a way that I won't give radium if they are not on the xgeva, it just isn't safe, knowing what we know. And so just sort of explaining the rationale, why there was an increased risk of bone-related events, and it's important that we have the supportive medication on board and the treatments kind of go together, it's layering. So they are on their androgen deprivation, and they are going to be on the radium, and they need to be on the Xgeva. So there are three layers of treatment, not only to treat prostate cancer, but safely.

Alicia Morgans: Yeah, and I think that patients really are supposed to be on these bone health agents to prevent skeletal-related events regardless of their treatment for metastatic CRPC. But I really, like you, take this as an opportunity to have a mental check and for anyone who maybe is getting radium in their first line for their metastatic CRPC or for whatever reason, hasn't yet started their bone health agent in that setting, it's nice to have that mental check.

I always think about bone health whenever we are getting into radium, and we move forward. And there are some patients who have really poor dentition or for whatever reason, refuse to have a bone health agent, but it is a good opportunity for us to talk with them. And nearly all of our patients are on these agents or start them as they begin their radium. So just another important thing for us to think about. And I know that some medical oncologists actually even partner with nuclear medicine to have a second set of eyes, to just check, "Hey, make sure your patient gets on that bone health agent." And this is, I think, just a way for us to keep ourselves ensuring that patients are getting what they need for their treatment.

So if you had to give, I guess, a summary or a final recommendation for folks who are considering how to best integrate radium into their practice, what would your message be?

Brenda Martone: To keep that on your list of potential options for patients who have CRPC with bone metastasis with any sort of symptoms. And again, that includes fatigue, weight loss, loss of appetite, and not just bone pain and offering this as an opportunity, knowing that the past doesn't predict the future. So because it is only for bone-related metastatic disease, you don't want to eliminate a treatment. So letting them know that this is the time to get this treatment under their belt. And the rationale for that is, it not only has an overall survival benefit, but if they are having symptoms, it has a palliative effect, which is definitely an improvement in quality of life. And then again, always thinking about bone health and making sure your patients are on their bone-strengthening medications to reduce any sort of bone-related event that could happen.

Alicia Morgans: Absolutely. So this is yet another tool that we have a way for us to try to help patients feel better and certainly live longer with that survival benefit. Thinking broadly about the definition of symptoms and getting every available therapy into our patients possible is absolutely our goal, while always considering other supportive measures, like attending to bone health. So thank you, it is always a pleasure to talk to you and just my joy to work with you every day. So thank you for your time today, Ms. Martone.

Brenda Martone: You are welcome and I reflect back at you that I love working with you too.