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Zach Klaassen: Hi, my name is Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center, and I'm pleased to be joined today by two folks who are friends of the website. And we're going to be talking today about the continuum of care among metastatic hormone-sensitive prostate cancer. I've got Dr. Jason Hafron, who is from the Michigan Institute of Urology in Michigan, and Elisabeth Heath, a medical oncologist at the Karmanos Cancer Institute. Thank you both for joining us today.

Elisabeth Heath: Thanks for having us.

Jason Hafron: Yeah, thanks so much for having us, Zach. We really appreciate it.

Zach Klaassen: So basically, the goal of this discussion is to talk about the collaboration between medical oncology and urology in terms of triplet therapy. We've had the ARASENS data for a couple of years now. So just to kick things off, how did you guys start collaborating together? How did we meet? Kind of a question. Let's start with Jason first.

Jason Hafron: Now you're getting personal. So we're fortunate enough, our practice is located in southeast Michigan. Dr. Heath, Elisabeth, is located in Detroit at the Karmanos Cancer Institute. So we're fortunate to have a national leader in prostate cancer, literally in our backyard. So when as urologists we got involved in advanced prostate cancer, we relied on Elisabeth to teach us, and we would frequently ask Elisabeth to come lecture the group. I know it started off with docetaxel. Elisabeth would come and lecture us on the indications and teach us a lot about prostate cancer, and we moved into genetics. So as much as Elisabeth wants to come, we always welcome her because she's always a wealth of knowledge for us to get better.

And then that transitioned to, we do research, and Elisabeth obviously does a lot of research as well at her NCI-designated cancer center, and there's a lot of synergy. Elisabeth does early-stage, late disease stage trials. A lot of those we don't. We do early-stage, early treatment trials. So we work together and we help each other find patients for our trials. When we're stuck on treating a patient or we have a tough patient, we'll send them to Karmanos, to Dr. Heath, and we hopefully can get them on a trial, or Elisabeth can solve the problem. So we give Elisabeth our hardest, toughest cases, and fortunately, she has the resources and the wherewithal to help these men.

Zach Klaassen: That's great. You mentioned something in your answer, Jason, about identifying patients. So maybe I'll ask Elisabeth, how do these patients, do they come to Jason, do they come to you in terms of urology, medical oncology? Maybe a little bit of both? How do you collaborate on these patients? How do you identify them?

Elisabeth Heath: I think that's the beauty of our working relationship. It really is working because it's constantly evolving. As the landscape changes, we're changing. And the reality is, most of the patients, whether it's in Detroit, Michigan, or elsewhere in the US, you're getting treated by the doc that's in your backyard in that health system. So we're from two totally different health systems, but I think we completely respect what we do and the service that we provide. And in doing so, I think in addition to what's new, I think it's also identifying patients that would benefit from one approach to another. When it was the CHAARTED data era and it was docetaxel, it was more of the, "Geez, are these folks chemo fit?" And those are really practical conversations that he would say, "I think you may want to learn more about this. I have a conversation. If it doesn't seem like it's going to be going towards chemo, then you follow back up."

And Jason, in your practice, I think over the years you guys have developed an advanced prostate cancer clinic, which really has elevated all of your care there so that you're asking your own urology folks, your colleagues, to also refer within. And in that sense, it's been really helpful for us. For folks, for I guess more of the ARASENS, we really feel like the high-volume and de novo presentation folks are the ones we really worry about. We know those, median overall survival is so much less, three years about, compared to the low-risk recurrent patients, overall survival around eight years.

So those are already day-to-day things that he and I look at individually and say, "I'm not sure if this person really warrants a referral. If they have no interest in trials, then that's a waste of both of our times." But most of the patients, Jason, that you send are absolutely happy to hear about other options. And if it doesn't work for them, then they feel like they had a moment to say, "Oh, I learned something. I'm going to move on, but really appreciate it." And maybe it's not then, it could be later. And that's really where I think it's been really productive.

Zach Klaassen: Absolutely. So when we've identified a patient, they're going to have triplet therapy, is there delineation to who's prescribing what? Obviously, we have ADT, we have darolutamide, and docetaxel. Who's prescribing what? I'll maybe ask Jason.

Jason Hafron: Yeah. I think Elisabeth and I have a good understanding, and she understands our practice. And I think that's the key. Even though we're in totally separate parts of the city, separate health systems, she understands what we do and what we do well. And for us, when we work with Elisabeth, we manage the ADT, we manage the oral agent, and Elisabeth will manage the infusion of the docetaxel. So that's pretty much already set in stone, and we don't really have to communicate that much. We just know each of our lanes. And then if Elisabeth has a cool trial or some alternative, she'll reach out and communicate, "We're going to go in this direction."

So I think it's not just that we know our lanes, but also when I send a patient to Elisabeth, it's an evaluation too, because it could be something I missed. It could be that she has a trial or some nuance that needs to be managed. But if it's just a straightforward ARASENS triplet therapy patient, I'll do the ADT, I'll do the oral, Elisabeth will do the docetaxel, and then we'll co-manage or co-survey for the patient's future. Because the other part of this too, which you don't realize, is that these patients will progress at some point. And the reality is, and Elisabeth knows this, once they progress after triplet therapy, as a urologist, we don't have a lot to offer them. And it's really where Elisabeth will step up and take control. So we kind of go back and forth, depending on the stage of the disease, on who will manage it. We do early stage, and then Elisabeth will come in and help us with these late-stage recurrences.

Elisabeth Heath: Zach, I think the other piece that always gets a bit missed sometimes is that a lot of these men have urologic issues; it's not just a systemic piece, where they really appreciate staying with a urologist. Sometimes, Jason, you've cared for these folks for many years. So there's a sense of loss sometimes when it's like, "Oh, well, everything will be done at our center." And my answer to that is, "Why?" If it's triplet therapy, you're like, "Listen, we're together for six of these, and then you go back and you come back if you need me." But a lot of them have issues: frequency, problems voiding, incontinence. I have no business in that particular arena. And they really like the fact that the continuity of care with their long-standing urologist remains.

Zach Klaassen: Yeah, it's a great point. And I think if I look at the mCRPC patients in my practice, it's a social visit. It's twice a year. I make sure they're urinating okay; we talk about sexual function. I think that's a great point, Elisabeth, because it's more than just co-managing treatment. We have our own set of things that we check on as urologists. So I think that's a great point. When you have these discussions with the patient, and especially you guys have a pipeline for a true triplet therapy patient, how do you discuss those with the patient when, say, Jason, you see a patient, you start them on ADT and the oral, you say, "Okay, we're going to go to Dr. Heath, she's going to talk about docetaxel"? How do you talk about that to the patients?

Jason Hafron: I think we've got to start and level-set their expectations. They have to realize they have a very serious cancer. And I think as urologists, we're used to downplaying prostate cancer. Here with these patients, we have to go in the other direction because the majority of prostate cancer I treat all stages, but the majority of what I treat is early-stage or localized. This is lethal prostate cancer. This is cancer. And if you look at SEER data, the five-year SEER data, which is about 30, 32% five-year survival using ADT monotherapy, that's the most lethal cancer a urologist will see in their clinic. And that's more aggressive than some of the bladder cancers we see. So I think as urologists, we have to appreciate that this is very serious cancer.

So my discussion starts off with laying it out: "We have a very aggressive cancer." I'm just thinking of the classic de novo patient: high PSA, high-volume disease, and we've got to be maximally aggressive. We can't sugarcoat this, we can't treat this lightly. This is very serious cancer that needs aggressive, full-bore treatment to get you to stabilize this disease. So I think I start with the expectations, and I tell them that, "We're going to throw everything at you, everything we have," assuming they're chemo fit, they're young, and they're appropriate. And that starts with ADT, goes to orals, and then we're going to layer in the chemotherapy.

In working with Dr. Heath and my local oncologist, I think as urologists, we've got to better understand the adverse or side effect profile of chemotherapy. And I think it gets overrated. And I think we have a responsibility as urologists to reeducate patients. The chemotherapy that we're talking about, docetaxel, is not this horrible thing. No one wants chemotherapy, but when you compare it to classic chemotherapy or what patients have in their mind of chemotherapy, it's a different beast. And I think that we've got to recognize it's a single agent, it's six treatments, four months total. Dr. Heath and the oncologist give various steroids to minimize the side effects. But I think that we've got to realize it's a single agent. It's not forever. It's like Elisabeth said, "I'm just going to treat you for a short period and move you on."

So I think as urologists, we've got to do a better job of educating about the severity of disease, recognizing that these are the patients that require aggressive therapy, and also level-setting them with their expectations for chemotherapy. And I was guilty of this early starting APC, overestimating the adverse side effect profile. Most good oncologists can manage docetaxel very well with minimal side effects. I don't know. Elisabeth, do you agree?

Elisabeth Heath: I do. And Jason, you're doing a great job because when you set that expectation, they're coming to me not freaked out. They actually appreciate that you're reaching out to talk about things like this. They know that it's a discussion and not a, "You're showing up for cycle one, day one, the day you see her." So I think they know it's just, "Let's see how you feel about this. What are some of the thoughts that I have as to why this would be an approach versus just pills alone?" And most of them, I think, really appreciate that you're thoughtful about it and that it is serious.

Actually, the last person, you and I just had a patient yesterday, the very words out of his mouth were, "My urologist thinks what's happening here is serious. He's never said those words to me before." So his wife was like, "I don't know what this means." I'm like, "Well, I think it means you're in the right place and we're going to have a discussion." So it really does help that we're not, in a way, the bad guy in the relationship. "Oh, here I come with the poison." It's more like, "What can we do to really address this serious problem?"

Zach Klaassen: Yeah, it's a great point. I think a great take-home point is the urologist has to set the table. If we're seeing these patients first, getting the medical oncologist on board, setting that table for that visit, I think is a great take-home point. I want to talk a little bit about the education to the patient. So who in your clinic is doing the educating about darolutamide, about ADT side effects, about chemotherapy? Maybe I'll start with Jason.

Jason Hafron: I am. I'm a community urologist in a large group. I educate them. We do have support. We do have in-house pharmacists, we do have navigators that also, but if I'm prescribing the drug or I'm giving the therapy, I have to know this cold, and I have to prepare these patients for what to expect. And God forbid a side effect or adverse event develops, I'm going to manage it. So fortunately, the quality of the drugs and the side effect profile of these drugs are very good, and I'm very comfortable, but I think as the urologist, as the physician, it's our responsibility to educate them on what to expect. So I would not put that on my nurses, I wouldn't put that on my pharmacist. They're additive. They definitely help when questions come up. I think also it's key to have the alignment that what I'm messaging or what I'm talking about is the same message that my pharmacist, my navigator, my nurse practitioner, everybody's saying the same thing so we don't confuse these patients.

Zach Klaassen: Excellent. How about from a chemotherapy standpoint, Elisabeth?

Elisabeth Heath: Yeah, same thing. They want to hear from me what I'm most worried about. So I always cut it down to the top three things that I'm concerned about. Because even when we give them the chemo care sheet, there are two pages of, "These are the things that you can expect." So that's one approach. And then I actually have our pharmacists go into more in-depth. So then they really, as we're consenting and going over each thing that they may feel on that day, to what happens that week, to maybe what happens that month, and then when you're done after four months, and then talk about long-term effects, they really feel like, "Oh, that's the second time I've heard it."

And then before they go, our nurse comes in and sort of the third time, "Are there any other questions? You understand this is what's been said?" And then if even all of that doesn't hold, on the day of treatment, we ask them to again spit it out. So it's more of an ask, tell, ask, "Here, how's this? Say it back to me. What are you thinking?" And then most of them are, they're ready. They're super informed. It doesn't take away that they're scared, but they're certainly informed.

Zach Klaassen: And the next question, as we get close to wrapping this up, is very important. And I'm really curious to hear your guys' thoughts, and you alluded to it a little bit throughout the discussion. You guys have a very unique system. Jason's a community urologist, different part of the city, Elisabeth at the NCI, the ivory tower. But you guys collaborate well in different specialties, in different systems, in different parts of the city. So I want to ask, because one of the questions we get asked quite frequently is, how do we collaborate? Are there barriers to the concept of "Are we able to share patients? Are we going to lose patients?" But in reality, it's about the collaboration, multiple sets of eyeballs. So I want to hear from you guys, and I'll start with Elisabeth. What potential messages to folks that are hesitant to share patients?

Elisabeth Heath: I think there's so much cancer to go around. Please don't worry about who belongs to whom. And cancer now is so multifaceted and so many people from different disciplines, we all need one another. And I think where Jason and I have been successful is we completely respect each other and our expertise, and we're aware of what's happening in each other's shop. So he knows the trials that I run, I'm aware of what he's running.

And then it's us both endorsing one another's importance in the treatment plan to the patient. Because if the patient doesn't see it and doesn't believe it, because the question I get is, "Well, but I come here all the time, can't I just get my shot here, or you prescribe the pills?" I say, "Well, I could, but I don't think that's in your best interest. Dr. Hafron's known you all these years. They have a system. They're literally 10 minutes from your house. He's been managing you with this, this, and this." And they're like, "Oh yeah." "And on top of that, you still have a lot of problems with your urination," yada, yada, yada. And then they go, "Oh, you're right. You're right. He's just not the prescriber." So I said, "More doctors as part of your team is always welcomed." And I think by both of us endorsing that, it really goes a long way.

Zach Klaassen: Yeah, that's a great point. Jason, anything to add to that?

Jason Hafron: No, I agree. I think we're successful because we respect each other's missions in our institutions. Elisabeth has a great understanding of how we operate and what's important to us. And it actually is very synergistic because at the end of the day, we have a tremendous amount of synergy that we can offer, and we're really not stepping on each other's toes. And I think it starts with that respect of understanding our mission, our business models, and what our goals are. So I think linking up with an NCI-designated cancer center is going to be a win-win for our patients because we are going to get the highest quality of care. We are going to get our patients and encourage our patients to join the phase one, phase two, the trials that we can't offer in the community. And that is really critical.

On top of it, just working with Elisabeth and her team, we've learned so much. It's raised our game. We look at Elisabeth's notes, "What's she doing? What's this new drug?" I'll send a patient over, the patient will get on this trial, and I just start learning about a new drug I never even heard of, a bunch of numbers and letters, that Elisabeth is offering to our patients. So it is important to respect each other, but it also can be obviously rewarding or improve the quality of care, but it also can be intellectually enjoyable to see what a GU oncologist at a major center's doing.

Zach Klaassen: Yeah. Great answers. It's been a great discussion. I'd love to give each of you a moment to wrap things up with maybe a couple of take-home points for our listeners. I'll start with Jason.

Jason Hafron: I think in this day and age, the ARASENS data is very provocative and very important. In the high-volume de novo patient, this is quickly becoming the standard of care, assuming that the patient's chemo fit. And I think that all these patients should be offered triplet therapy or should be at least offered the opinion of an oncologist on what they think is best for treatment. Low-volume, low-risk patients is an option. I think it's a discussion, but I think where in our practice, when we see these high-volume de novo patients, that's a patient that requires triplet therapy.

Zach Klaassen: Elisabeth, you have the final word.

Elisabeth Heath: I think Jason said it so well. It's also just in addition to us working together, it's knowing the patients you're serving and what their capacity is and meeting them where they're at. And I think we've both been really fortunate by working together to be able to understand who our patients are and what's the right treatment plan for them. So really important to recognize who you're serving.

Zach Klaassen: That's great. You guys have a great collaboration and we thank you so much for sharing that with our listeners today. Thank you both very much for your expertise and time.

Jason Hafron: Thank you, Zach.

Elisabeth Heath: Thanks for having us.