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Zach Klaassen: Hi, my name is Dr. Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center, and I'm pleased to be joined today for a UroToday discussion with medical oncologist Dr. Chandler Park, who is the co-director of GU Clinical Trials at the Norton Cancer Institute and Advisory Dean at the University of Louisville, and urologist Dr. Ryan Malone, who is the Clinical Director of the Advanced Therapeutic Center at First Urology in Louisville. Gentlemen, thank you both for joining us today.

Ryan Malone: Thank you.

Chandler Park: Thanks for having us, Zach. Great to see you.

Zach Klaassen: You too. So, we're going to discuss basically the continuum of care for metastatic hormone-sensitive prostate cancer and really focusing on the collaborative approach between GU medical oncology and urology for managing these patients with triplet therapy. And so, I guess just at a high level, how did you guys find each other? What's your setup at your clinics, and how do you collaborate with certain patients?

Chandler Park: Yeah. I'm very fortunate, being from Kentucky and from the Fort Knox area, kindergarten to 12th grade. And so, I've been practicing here for close to 10 years now, and I had an opportunity to work with a lot of different urologists. Dr. Malone and I, we met each other through meetings and also developed a relationship. Then it just progressed to the point where we're seeing patients together. I'm very fortunate because Dr. Malone is so strong clinically and also very knowledgeable, and patients love him. Ryan, what are your thoughts about how we met up?

Ryan Malone: I think it was just that we naturally had a similar interest and met not only through conferences and through the discussion of material but also through shared patients that happened naturally. I think as we had more and more common patients, we gravitated toward each other in terms of clinical collaboration. We've had a lot of outside discussions, specific to certain patients. Then also from a higher level, about philosophy and approach to addressing these things and how having co-management is so important to some of these disease states.

Zach Klaassen: Yeah, and we're definitely going to get into some of those aspects for sure because I think that's what our listeners need to hear. The collaboration is really the key for these patients. When you guys are either seeing them first, maybe medical oncology sees or urology sees them first, what's the typical patient you guys are looking for to start with triplet therapy? Maybe I'll start with Chandler first.

Chandler Park: Yeah. We were very fortunate to work together with First Urology, which is the main great urology group here in Louisville. We actually participated in the ARASENS study with First Urology, and we were actually the leading enrollers in the whole country with First Urology.

I think the main thing with the ARASENS Study for me for the patient population is two things that I think about. Is the patient with stage four metastatic hormone-sensitive prostate cancer, is it a synchronous presentation, or is it a metachronous presentation? If it's a synchronous presentation, that portends a very aggressive cancer, and then also metachronous, if they've had the prostatectomy or radical radiation treatment and so on.

Then within that subgroup, there's are four quick boxes I'll put patients in, high risk, high volume. What do I classify as high risk? It's based on the LATITUDE Study. In that study, patients with three or more bone mets, if they had Gleason 8, 9, or 10, or if a patient had visceral mets. So, if they have two out of those three, they're considered high risk. And so everybody with high risk, I do triplet therapy.

Now, what about high volume? If a patient, based upon the CHAARTED study, if a patient has four or more bone lesions and one outside of the spine and pelvis, that's considered high volume, and that's what I consider. Also, the patient's factors. The patients always see Dr. Malone first, and so I trust his judgment. Some of our patients may be older, maybe not as strong, they can't tolerate chemo because nobody should be getting chemotherapy by itself. So, I rely on him when he sees the patient and he lets me know before I see the patient. Ryan, what are your thoughts?

Ryan Malone: No, I would echo your comments, and I think it's really important that, Dr. Park does a nice job of being humble, but it's important to note that when I see a patient who I think might be a candidate for triplet therapy, I really rely on his judgment on whether or not chemotherapy is appropriate. I don't send them for chemo. I send them for truly his evaluation, and also as a check, and a collaborative approach, to make sure that I'm evaluating them fully and appropriately, and to make sure that I've considered all the comorbidities when we're adding all of these therapies together. When we choose the oral-oncolytic agent, sometimes that decision, because of coverage, does depend on whether or not the chemotherapy is going to start. So, the communication that we have is really critical, and the timing is critical for coverage. So, to get those patients optimized and optimized quickly, when they are in the setting of being on fire, so to speak, our communication is what allows that to happen.

Zach Klaassen: That's great. It sounds like Ryan's sort of the triage guy. Who prescribes the medications? Do you guys divide it up, or how do you do that from a logistical standpoint?

Ryan Malone: Often, we manage the hormone and the oral-oncolytic here through our office, and then, of course, the chemotherapy is done through Dr. Park. There are times where those patients will present through Dr. Park for whatever the referral pattern is, and if he sees them first, sometimes those patients are prescribed those medicines there. I think it's just a really important point of the communication to make sure that we communicate as to who's doing what. But typically, it's who sees them first starts the process.

Zach Klaassen: Yep. Chandler, when you discuss with these patients about chemotherapy, obviously this is a six-cycle hard stop. Is there are there any specific factors that you maybe highlight for the patients?

Chandler Park: Sometimes you have to think about, does this person have a history of heart failure? Are they going to have leg swelling? Things that I look at, and Dr. Malone does a wonderful job, is we are doing more and more liquid biopsies, and Dr. Malone does the germline and somatic testing. And so, if they have a PTEN, Rb-1, P-53 mutation, I consider that as high risk, and so I would consider that for chemotherapy. On the other hand, if they have an S-pop mutation, they might not need a triplet therapy. Those are the things that I look at. Now, once I talk to the patient, I use the stand and go, if the patients can move around, because you're going to get a lot of neuropathy. So, if they get up out of a chair and they're stumbling, that might not be the best candidate for triplet therapy.

Zach Klaassen: Yeah. No, that makes sense. When you guys see these patients, and you've already decided on triplet therapy, do either of your practices have educational services? Or who's doing that to really give the patients and their families the best understanding of what they're getting into? Maybe I'll start with Ryan on that one.

Ryan Malone: Yeah, I think it happens in about three or four different places, and I think it's reinforced each time it occurs. We have a fairly robust handout that we put together in terms of the ADT and the oral oncolytic. I don't give out a lot of information other than verbal about the chemo. I'm not managing that portion of it, nor honestly taking the phone call when they have issues, so I really need that for Dr. Park and his team. But they get a lot of that information. They get handouts, they get some of the industry-sponsored pamphlets that are available as well, and we give them websites that they can reference also. We have an in-office dispensary. They have that direct contact and that number, and our staff there, who knows how to triage those folks. They have that information with them when they go and see Dr. Park, and then he can double down on that information, as well as add the things he needs to add.

Zach Klaassen: Yeah. Chandler, how about you? In terms of specific chemo handouts or how do you educate them?

Chandler Park: Yeah. First of all, I think when cancer patients hear the word cancer, it's overwhelming. The more often that the team members mention about the different treatments, I think the more it sticks. I know Dr. Malone and Rhonda that works with Dr. Malone, they do a wonderful job talking about the oral oncolytics and helping us talk about the chemo.

Now, in terms of the medical oncologist side, we have a nurse clinician, an OCN-certified oncology certified nurse. She goes through all of the side effects of chemotherapy, and also we highlight some of the side effects of darolutamide. Then, if the patients start getting into trouble with more pain, we have a dedicated palliative care team with a dedicated palliative care certified physician. We have nutritional services, and we also have an interventional radiologist. So, it requires a team effort, but we do all these things like in terms of teaching about chemotherapy. Dr. Malone starts, Rhonda, she talks, then the OCN, the pharmacist, and then myself. And so, I think the patients end up hearing about the chemotherapy and the side effects four or five times during their journey.

Zach Klaassen: That's great, and you have a full multi-D team there, especially with palliative care and nutrition. That's fantastic. So, you guys obviously have a great relationship, and I've got a great relationship with my GU medical oncologist, but let's say somebody listening is unsure of the sharing of these patients, perhaps there's a bit of a fear of losing patients. What would your message to those listeners be? Maybe I'll start with Chandler on that one.

Chandler Park: Well, I think it's from the medical oncologist perspective because that's the only one I can speak on behalf of. I think we just have to emphasize that patients, they would get the best care if every team member's on board, including the urologist, and the patients develop a relationship with the urologist. So, once they start getting chemotherapy or once they start seeing a medical oncologist, we have to manage up the urologists that are seeing that person, because I always try to put myself in the patient's shoes. If the patient's getting one message from the medical oncologist and getting a different message from the urologist, it causes confusion and distrust from both physicians and then just healthcare in general. And so, the only thing I would say is, take the time to get to know the people that you're working with, the urologist. I think Ryan Malone's wonderful. Then, if there's any discrepancy, talk to the urologist directly and then handle it that way rather than just bringing anything out in front of the patients.

Zach Klaassen: Yeah. Great points. How about you, Ryan? I know as urologists we can be very... We have long-term relationships with these patients, right?

Ryan Malone: We do, and I have sort of a different take on it, maybe. I like to get them involved with Chandler very early on, even if I don't think they're maybe going to get triplet therapy right up front because these are metastatic patients. They're going to need Dr. Park and his services at some point in their journey. If they can meet him early on, have a relationship with him that he can grow with them, when it is time to pull the trigger for them to intensify their therapy, then they've already built a relationship and have some trust with him. I think that's really important.

His approach to patients has always been one of, he's not just taking them to, it's not just do what is sent to him. He's making a real evaluation. Sometimes the conversations are a phone call and go, "Hey, I'm really looking at it this way. What do you think? Maybe we should pivot," and he's right. It keeps us both on our toes and helps us approach what he said, as making sure the patient's getting a consistent message. There's nothing more frustrating than seeing a provider who gives you one message that's contradictory to the other expert they're seeing. I don't know how you manage that as a patient. So, if we don't create that environment, then the patient is who loses.

Zach Klaassen: Absolutely. I think one thing I'm pulling out of our discussion is communication amongst ourselves is huge, right? It's a quick phone call, it's a text, it's making sure we have aligned talking points for the patient, right?

Ryan Malone: Yeah. We communicate a lot, but that makes it sound like we're taking a significant portion of our day on the phone with each other. That's not the case. Sometimes it is a four-word text. It can be very, very quick, but it can really change that care delivery.

Zach Klaassen: Yeah, absolutely. I want to get into just a little bit of the nuances of the ARASENS data. Is there any aspects of the data, we know the survival data is strong, are there any aspects of maybe the secondary analyses or some of the post-hoc analyses that you guys focus on when you're talking to patients about triplet therapy? Chandler, why don't you start with that one?

Chandler Park: Yeah. We kind of know the data with the high risk, high volume. Dr. Maha Hussain did an update at ASCO GU last February, so there's some data there with even low risk. But I think for me, I always try to get to know the patients. Is this possibly the last treatment that this patient might receive? In that case, this might be my last shot. Some of the facilities, based on the flatiron data, only 50% of the patients even get to chemo, and so this might be the last treatment. Then the other thing that I think about is, if they do the doublet therapy and they need the second treatment, it's not going to be six cycles of Taxotere, it's going to be 10 cycles of Taxotere in a castrate-resistant space, and you're looking at maybe six or seven months of benefit. So, those are the things I think about. Not just the data, but also, are they going to get to the second line treatment? If they get to the second line treatment, can they handle the 10 cycles in a castrate-resistant space?

Zach Klaassen: That's a great point. Absolutely. Ryan, how about yourself?

Ryan Malone: Yeah, Dr. Park frames that in such a more eloquent way than I do, but I really think about it as how do we keep them on their journey and how do we make sure that we don't lose that next step in therapy? Like you said, there's a drop-off in who gets to chemo. I think part of the job of the urologist is to make sure that we are mentioning the word chemotherapy and explaining that, hey, this upfront doesn't mean this is the end. It's really important to understand what that chemotherapy means. It's not a four-drug regimen where all your hair's falling out, and you're pushing an IV pole down the hospital hallway. That's what patients hear.

So, if you explain that to them up front, then when Dr. Park delivers that message again, explains why it's important, they have a different mindset walking into that conversation. Again, back to the data, thinking about who's going to tolerate it, if I can introduce that and we can get it in front in these high-volume patients, then you're right, they get fewer cycles and maybe they get more benefit by delivering that early.

Zach Klaassen: Yep, absolutely. Gentlemen, it's been a great discussion. Just to wrap things up, are there any take-home messages you'd like to share with our listeners? Maybe something we haven't hit on? I'll start with maybe Chandler for this one.

Chandler Park: Yeah, yeah. I think the key is just to, even though the statement we always say, is "putting the patient first," but putting the patient first requires a lot of responsibility, trust, managing up your co-physicians, and also availability. I know we're all extremely busy, but if Dr. Malone calls or somebody calls, if I get that message now, then I can start working on that problem now. Because if Dr. Malone or another physician's calling me, that means a patient needs help. And so, I think it's just about availability and just be working together, like with communication, like you said, Zach.

Zach Klaassen: Yeah, that's great. How about you, Ryan? Final words?

Ryan Malone: Yeah, communication. I can sum it up in one word. I just think you have got to be available. But again, I want to emphasize that that doesn't mean that it has to take an extraordinarily big part of your day. It can be very, very brief. But it's not just simply about faxing this message over to that office. Sometimes it needs that personal touch. "Hey, Dr. Park, this guy's coming over. You've been seeing him. He's now a candidate for a PARP, and his hemoglobin's low. I just wanted to alert you." Something as simple as that sometimes, or-

Chandler Park: Zach, I forgot to mention, real quick. One more thing is, for me, I think I have a sincere interest in this, and Dr. Malone does as well. When you have a sincere interest in something, with clinical trials and working together, and Dr. Malone is very humble, but we're doing some of the leading clinical trials across the country because of communication and working together. We're doing this bladder study with the Sunrise Study, and this is something that would not be possible without a close collaboration among oncologists and urologists across the country. So, Ryan, what are your thoughts about collaborating for research and having tomorrow's treatment in a close community, close to where we are?

Ryan Malone: Yeah. Some of this care delivery isn't possible without both specialties working together. The Sunrise is one example, but it's an example where an immunotherapy that I'm not providing, I can't do that trial. The patient doesn't have access to that care if Dr. Park and I don't work together. So, I think this collaboration, in situations of treating patients in a triplet therapy fashion, if you can figure that out, it opens up the door to those other relationships and other care deliveries.

Zach Klaassen: Absolutely. Lots of great points today, gentlemen. I really appreciate your time and expertise, and thank you very much.

Ryan Malone: Thank you.

Chandler Park: Thanks, Zach. Appreciate your time.