Alicia Morgan: Hi, I'm so excited to speak again with Dr. Neal Shore, this time about how we really optimize the multidisciplinary care team as we think about radiopharmaceutical administration, in particular radium-223. Thank you so much for talking with me today, Dr. Shore.

Neal Shore: Oh, great pleasure for me. Thank you, Alicia.

Alicia Morgan: Wonderful. So, Neal, I know that you've been thinking about this for years, radium of course been around for years and you have a practice that is extremely active, particularly within the advanced prostate cancer population, that you care for some men over many years. I'm wondering how you work in your urologic practice to really collaborate with nuclear medicine doctors or radiation oncologists, medical oncologists, to give treatments like radium, which is a drug that, of course you can't give on your own and neither can I. How do you do that?

Neal Shore: Yeah, well, we have a great multidisciplinary communication. We have virtual tumor boards. We had in-person tumor boards. Actually, we found since COVID, we've been doing a lot more on the virtual side, but the other part is I have had three fantastic radiation oncologists, five fantastic medical oncologists, and we're all on speed dial. There's a text or a dial and the communication is instant. That's how we've really done it. We don't have the luxury of all being under one roof. I will say that we also collaborate extensively on clinical trials. We collaborate extensively with the use of a pharmacy that my medical oncology colleagues have. So, we all work really very nicely together. They send me many clinical trial referrals.

For the radiation oncologists, they've really been wonderful in procuring their radio activities materials licensure. Back in the day when they needed to do it for radium-223, they were really keen to get it early. And we were lucky enough to be the first site to administer radium-223 post FDA approval. That seems like a long time ago, was 2013. But even now they're working very assiduously to get their unique RAM, Radio Activity Materials license, for administering lutetium and then even for administering some of the newer PSMA PET scans where you need additional RAM licensure.

As to your point, I don't have that and these are all controlled by the Nuclear Regulatory Commission, both federally and even on a state-by-state basis. And so, you have to know your state's NRC requirements, but once you can do that, then you can do clinical trials. You can offer approved therapies as we're doing, and that's been the secret sauce and it's not so secretive. It's just really very transparent and clear communication.

Alicia Morgan: So, I think to your point, communication is absolutely key, whether you're doing it in a virtual tumor board, whether you're doing it because you're just calling down the hall to somebody or whether you're texting them or calling them. I think that is so important. Now, I wonder how you and your team actually communicate and collaborate around radium treatment, which of course we could extrapolate to other therapies too. But radium is a treatment where we need to actually get a CBC at some point. Usually a week in advance of treatment administration, because you have to clarify and confirm that someone is going to be safe for administration and then order the drug of course and have that delivered. So how do you work around that as a urologist? Do you give that to your nuclear medicine team or your radiation oncologist to own? Do you own it? And then how do you communicate safety back and forth with the rest of the team?

Neal Shore: So, we try to make it as easy as we can for our radiation oncology colleagues. We would use nuclear medicine. Our nuclear medicine radiology colleagues in big hospital community centers. They're not administering it. We do the CBCs. We take that off of the hands of our radiation oncology colleagues. They're happy that we're doing it. We do lots of blood drawing and we start IVs. So, we've got good venous access within our clinic, both in my research and in the clinic. And so, we check that regularly. We check that regularly if we're giving a PARP inhibitor. And as it relates to the safety, here's the thing that's really so encouraging. I remember when radium first came out back around 2013 and everyone was like, oh my gosh, this is going to be like strontium and samarium.

And these are really tough drugs. And patients are going to get super sick. Far from it. Radium is a large alpha particle. And because of that, it is a totally different safety profile from the beta gamma particles such as strontium and samarium. Totally different. So, what does that mean really in practical terms, the patients there's no pre medication, there's no post medication. It's literally a 60 second peripheral IV infusion given by their radiation oncologist, or your NUC med radiologist patients are just simply instructed to be hydrated, which is like saying, remember to keep breathing, if you're a urologist. We tell everybody to be hydrated throughout any oncologic or non-oncologic treatment, and then that's really it. And then afterwards, their precautions are just basic universal precautions, no special precautions in terms of having to exclude them from being in a room with a loved one or anything else.

I mean, if they have any bodily fluids, they just would be use appropriate precautions. It's a little bit different for the PSMA RLTS. It's a much more restrictive precautions for those drugs. But having said that it's mostly, if anything, some very low grade, one grade, two diarrhea, which I rarely see in all my years of administering therapy, I've never had to start an IV for hypovolemia related to diarrhea. I've never admitted a patient. Gosh, I've now treated a couple hundred patients with radium. So, this is really I think an important aspect.

And yet I still think there's many of our colleagues in the US, outside the US, who think that radium may be more challenging to administer and/or more difficult to tolerate. And I think that's still very disappointing to me because it's such a perfect drug to give throughout the spectrum of the mCRPC journey. I will say we're actually going to be starting a trial. I'm really proud of to be leading in the US. We may take it outside the US called the CARE trial, and we'll be looking at mCSPC patients receiving ADT and an AR pathway inhibitor plus minus radium 223. Pretty cool. So, we're taking it into the mCSPC population and largely because it is really well-tolerated drug. And of course, this will be in bone-dominant patients and patients without visceral metastases.

Alicia Morgan: Well, I think that's really interesting, and I do hope that we see at the conclusion of that trial, that there might be some synergistic benefit. And again, earlier use of drugs tends to give us a better or a bigger bang for our buck. That is highly anticipated. And congratulations on putting that together. And I would just say that the way that you and your team work together sounds wonderful, but whatever way we can work with our colleagues in radiation oncology, nuclear medicine, whatever we can come up with. I think it's important to have a strategy, to have a style, to have a way to confirm safety and to communicate with our teams so that we can get every single possible agent to every patient who can tolerate it because we may miss the opportunity of treatment for radium. If we really delay and use it only at the end of the line as a palliative treatment. And it would be a shame to leave something on the table that could be helpful for our patients. So, I thank you so much for talking this through with me. I appreciate your time and your expertise.

Neal Shore: Thanks very much Alicia.