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Alicia Morgans: Hi, my name is Alicia Morgans and I'm a GU medical oncologist. Really happy to be joined today by Dr. Rana McKay, also a GU medical oncologist.

Rana McKay: Thanks so much for having me. It's great to be here.

Alicia Morgans: It's great to be here because I think we really need to talk about an important topic for patients and for clinicians, which is thinking about how do we sequence treatments when it comes to advanced prostate cancer, especially when we think about metastatic castration resistant prostate cancer. This is a setting where patients have had their disease move forward in the earlier settings, and there's a lot of treatment options here, right?

Rana McKay: Yeah. No, I think the treatment armamentarium has really been exploding. There's hormonal therapies, there's targeted therapies with the PARP inhibitors. For select patients there's even immunotherapy, of course, there's chemotherapy and there's even radioligand therapy, which has now entered into the treatment landscape. I think selecting between those different agents can sometimes present a challenge to think about all the different factors to weigh in when selecting any one given therapy for any given patient.

Alicia Morgans: Yeah. I think what's so important is we include patients a lot of times in those discussions because so many of the things that we think about are really dependent on what the patient wants to do and how the patient is feeling and their strength, their function, their blood counts. All of these things can weigh in. When I talk to patients, sometimes the things that they talk about are they want to be able to go out and keep doing the things that they need to do or want to do, like taking care of people or spending time outdoors and having fun. Sometimes hair loss can be something that they think about or being concerned that they might be at risk for an infection. These are just some of the things I hear about. What things do you hear about from patients that they struggle with as they're trying to make these choices?

Rana McKay: Yeah. I think that's a huge thing is their ability to continue to be high functioning individuals with their family and loved ones and caregivers. I think the mode of administration of different kinds of therapies matters. Some therapies are given in pill form. Some therapies are given as an IV infusion or an injection, and I think that also impacts decision making. The side effects of any given regimen; what's the likelihood that they may end up with an adverse event that may result in them feeling unwell or ending up in the hospital? I think these are all things that we think about. Of course, efficacy matters, but there's a lot of other things beyond efficacy when we have a lot of different treatment options that are all slightly unique in the way that they're administered and their side effect profile and mechanism of action.

Alicia Morgans: Yeah. Thinking about efficacy or really how well the treatment works against the cancer, what I think is so fascinating is in this setting, metastatic castration-resistant prostate cancer, most of the benefits in terms of how much more these treatments make someone live or how much they can increase the amount of time someone's alive, it's actually really similar across all of the options, which makes it tough to choose one of the treatments based on disease control or cancer control alone.

Rana McKay: Yeah. No, absolutely. I think there's a lot of things to weigh in. A lot of times the decision making is based off of what patients have seen before, what's going on with their disease at the present time, where are their sites of metastases, what's happening? Those are, I think, the clinical things that we take a look at, but it's critically important to also weigh side effects of therapy, how therapies are given. How does that therapy integrate into somebody's life plans, like if they're intending to travel or go see a loved one or do something or have a major trip coming up, that is important to think about how to sequence any one given therapy.

I think what's been really unique in prostate cancer is the introduction of all the radioligands, which is really novel and exciting.

Now there are two FDA approved life prolonging radioligand therapies in prostate cancer, which is excellent, but they're very different in the way that they're given and also in their side effect profile, and the type of radiation does matter. For example, alpha therapies have a very short half-life. They're in circulation for a very short period of time. Their focus is directly in the tumor microenvironment. They don't tend to cause too much toxicity beyond that microenvironment with regards to fatigue and affecting the bone marrow counts.

I think sometimes there can be some fear that's associated with radioligand therapy. I think there's this notion that I'm going to be lighting up when I get a treatment and how is it going to affect my loved ones and how is it going to affect my grandchildren that I may be hanging out with? I think the beauty of an alpha emitter is that it's pretty short-lived, and it has a very short half-life with a focused range of activity as compared to beta emitters, which tend to have a longer half-life, they're in your system for a longer period of time, and there can be some other, at least with the radioligand therapies, PSMA, for example, is expressed in other parts of the body beyond the prostate cell itself, so sometimes it's a misnomer that it's prostate specific membrane antigen, so there can be some other on target effects, but because the target is found in other parts of the body.

Alicia Morgans: Absolutely. I guess in simplest terms, when I think about an alpha particle, this is something that should not make someone give off radioactivity to people around them. It's really that particle's not going to get beyond the outer part of their bone, let alone probably even just microns in the microenvironment of inside their bone marrow, so it's not going to make them glow in the dark. It's not going to make them radiate anybody around them, but when we think about treatments that are beta particles, they are going to give off some radioactivity.

In general, we talk about people staying away from others, adult others for about three days and trying to keep their distance so that they are not giving someone a radioactive exposure. For pregnant women and for children, they do need to spend longer away, so seven days is usually what we say in our center. These are just some differences. To your point though, the other things that these agents can radiate can cause some of the side effects as well. There are definitely differences, but they're both still part of the options that we have for treating metastatic castration resistant prostate cancer.

Rana McKay: Yeah, absolutely. I think with the alpha emitters, they're really focused on a two to 10 cell radius. That's where their activity is, so there's really little activity beyond that diameter, but with the beta emitters, it's a little bit different. There does need to be additional precautions with regards to being around loved ones or sharing a bed with somebody for a prolonged period of time at night, and thinking also about bodily fluid and having a separate bathroom and making sure that there isn't any release of radioactivity through bodily fluid, urine, stool, saliva, things like that. Yeah.

Alicia Morgans: Absolutely. Well, if you're trying to make these choices with patients, I can tell that you're thinking about a lot of important things. Anything else that you want to add in as we wrap up?

Rana McKay: I think treatment decisions can sometimes really be an opportunity to understand where the patient's values are and what their goals of therapies are, because I think every patient that we encounter in the clinic has a different priority set of things that are really important to them. I think whenever we're at that juncture of deciding what to do for any given patient, it's really important to just step back and understand, okay, what are our goals of therapy? Yes, to make you live longer, but to make you feel better, make sure you're high functioning. What is going to be the therapy that really allows us to do that in the best way? I think it's really important to do that when you're deciding on a therapy.

Alicia Morgans: Absolutely, and for patients to feel empowered to say, hey, these are my goals. This is what I'm thinking about. This is what I'm afraid of. This is what I don't want to happen. Those conversations can really be so important in helping make sure that the patient gets the right treatment for him. That's what we all really want at the end of the day. Thank you so much for talking this through with me.

Rana McKay: Of course. Yeah. No problem. Thank you.