Neal Shore: Thanks very much, Tanya.
Tanya Dorff: So I wanted to ask you a little bit, in the prostate cancer world, prostate cancer patients can be treated in different sections of the healthcare system, sometimes by urology, sometimes by medical oncology. So as a urologist who treats advanced prostate cancer, I wanted to get a sense, what do you hear from your colleagues is most impactful when they find a patient newly diagnosed with metastatic prostate cancer? How do they approach the treatment decision-making that's gotten more complex lately?
Neal Shore: Yeah, it really has, which is great product of all the great research and trials that everybody's been involved with at the academic level, at the community level, and the global level. I think it's really been great for the field of urology and uro-oncology because we've moved way away from just, well, you just give them a testosterone suppressor and call it a day and all our articles and all this homage and appropriately so to Huggins and Hodges. But boy, the field has gotten a lot more interesting, a lot more complicated. The importance of genetic testing, the importance of understanding doublet ADT with choice of ADT and the choice of an ARPI, and the potential for even considering triplet therapy. Great studies recognizing the value proposition for adding in six cycles of docetaxel. I think what I've seen in the urologic community is a recognition that you just can't give ADT and call it a day, even though the PSA may come down very low.
We have this embarrassment of riches now of four different drugs, oral drugs to give, and not everybody's comfortable in giving it. I think if you're a general busy urologist, you may not have the ability, you might not have the access to a pharmacy or an in-office dispensary. You may not want to be bothering in the US with specialty pharmacy. You can't write the script and send them to the local nearby CVS. So I think multidisciplinary teamwork is essential if you're in that camp. If you're in the camp where you say, "Okay, I get this. I'm following the literature. I understand how to monitor these patients with different lab work depending upon the ARPI you choose, have the conversation with the patient, and then think about their overall care, their bone health, all the different side effects that we see with doublet therapy." And then the consideration for triple therapy. What I want to see less of is monotherapy ADT. And some recent real-world data that I've reviewed, we still have upwards of 25, maybe even 30, 35% of patients still getting monotherapy ADT. I understand there may be certain types of patients that you may only want to do that, but I think it's probably should be no more than 10%.
Tanya Dorff: Absolutely I agree. But so how do you manage all of that? Do you work with a primary care physician to help with some of the things you talked about like bone health, cardiovascular health, metabolic, or do you take that all on yourself? Do you partner with medical oncology?
Neal Shore: So I personally, in our clinic, we take it all on by ourselves. So I've been very involved with understanding the evolution of bone health agents, starting with great work that Fred Saad did with bisphosphonates and then the RANK ligand monoclonal antibodies, and then vitamin D and calcium supplementation, regular exercise, good nutrition. These are all, to me, all part of the comprehensive plan. My dad was a general practitioner, became a family physician. My great respect for the PCPs, the primary care physician, they're overwhelmed. If you have one who has a real interest in oncologic care, hey, that's fantastic. Partnering with your medical oncology community, the radiation oncology community, just as long as patients are getting the right exercise, nutritional, bone health protective agents, exposure to the conversation of doublet versus triplet, helping them get through sometimes the economic issues. There should never be any internecine competition or warfare with the specialties. It really is about the north star is putting patients first. I see more and more multidisciplinary clinics opening up med-onc embedded within a urology, large practice. Everybody's moving towards scale or even urologists embedded in medical.
To me, it was never about who gives the drug as long as the drugs are given appropriately, patients and their caregivers are explained in a very careful way and that there's good shared decision-making. Everyone's busy or you have a person power shortage. Having your colleagues on speed dial, doing virtual tumor boards is how we've been approaching making sure that we don't miss and that patients get the right care.
Tanya Dorff: So what are some of the key drivers? I heard you mention a little bit about prescribing potentially being a challenge. So maybe insurance coverage drives our practices a little bit, but when that's not an issue, how are you approaching that decision between abiraterone versus an AR antagonist? And is there one that becomes easier to prescribe in the midst of comorbidities and drug-drug interactions?
Neal Shore: A quick response right before that is thank goodness that we did get the Inflation Reduction Act, because that was a really nice example of where Republicans and Democrats during the Biden administration got together. So they lowered these copays universally for expensive part D drugs. And that was really good. I mean, we went from really high multiple thousands of dollars for copays. I think now in 2026, it's down to $2,100. Next year, I think it goes down to $1,800, if I'm not mistaken. So that's really good for patients. Still, for some, it's a lot of money. In making the decision, I try to stay as, I won't say agnostic, but I really have great respect for the development of abiraterone, enzalutamide, apalutamide, darolutamide. These are all really active drugs. And I try to, because there's only so much time in the day that you can spend with patients. I wish I could say I had unlimited time.
Unfortunately, I don't, but I try to distill the conversation to lab testing, adverse events, particularly of interest that I think might be more concerning from one patient to another. Assuming that cost is not an issue, sometimes it could be something as simple as pill count, dosing, food effect, and I try to go through that. And then, there's always drug-drug interaction and some folks who have polypharmacy issues. Sometimes I almost never do sequencing when patients are progressing by PSA or radiographic, but I may sequence if someone's having intolerability. In fact, we frequently we do, for whatever reason, they attribute something, a side effect may be clear, may be unclear, but I'll switch early if a patient's saying, "Look, I'm just not tolerating X, Y, Z drug."
Tanya Dorff: Yeah, I agree with you. They're all very active. I will say that STOPCAP analysis shifted me a little bit away from abiraterone in older, more frail patients where I would've thought there was an advantage, but it looked like in that dataset, at least that the AR antagonists were actually somewhat better because I do worry about my patient who was playing tennis and now can't play tennis anymore and the amount of muscle loss or cognitive change that leads to those. So it sounds like you have to be fairly agnostic and yet you can't really present all four options and we all develop practice patterns. Are there certain agents that you prefer when you're using a triplet?
Neal Shore: Well, I mean, if you look at the, you've got PEACE-1 and ARASENS data, and basically that really is supportive of abiraterone and darolutamide. Typically, maybe I'm biased because I was part of the ARASENS trial, so I'll use darolutamide when I'm giving a triplet. I think it seems to be very well tolerated. Look, I get genetic testing on everybody, to your point, STOPCAP, great study, great analysis. But if somebody has an SPOP, that may lead me towards using AbbVie potentially in that patient. I'm excited to further see how we refine this discussion with PARP inhibitors. Also now, we have the ADDITION trial, which is positive, but we'll see if that gets regulatory approval for using lutetium. And there are some other really exciting other PARP triplets that we're going to be looking at, TP3 will report out. And so, trying to balance which ARPI to pick. There are a lot of interesting mCSPC work going on with different EZH2s, so that'll be another triplet and how we reckon that. But I think it's really good. And I'm hopeful that in meetings like ASCO GU and AUA and ASCO, ESMO, et cetera, EAU, we continue to get the education front of mind. But at the end of the day, get back to, I love the multidisciplinary approach, bringing folks, working better together and having that really good discussion through some form of a tumor board.
Tanya Dorff: I think it is getting increasingly complex. It's great to hear that you're getting genetic testing, I imagine, germline, and now the push for somatic testing right up front as well, given these novel triplets. And that I think we'll shift our practice. If TALAPRO study used one ARPI backbone with their drug, we know you can't mix and match. So that's going to either limit who we put on that triplet if they're not good for that backbone or limit our use of that backbone to a different backbone that we might like because this is the one that you have to use in this combination. But PSMA addition, I think with lutetium PSMA allowed any of the ARPIs, right?
Neal Shore: That's right.
Tanya Dorff: So that leaves it wide open.
Neal Shore: Wide open. But again, your point, I've been getting, I try to get 100% germline and somatic NGS in all my mCSPC patients, whether they're de novo, recurrent, and regularly high volume, low volume. I just want to have that in my arsenal so I can inform patients and their family members.
Tanya Dorff: Excellent. Well, anything else you want to add for urologists taking care of metastatic hormone-sensitive prostate cancer, which we will soon be calling androgen pathway modulator naive.
Neal Shore: I know. I got to wrap my arms around that. I got to download the article on PCWG4. I got to get it. And I don't know. I don't know if I'm ready for another acronym, but what are we without more acronyms? I think it's super important to stay up to speed with the literature if you're going to see these patients. And if because you're so busy being a surgical oncologist or if you're busy doing other non-oncologic things, it's okay to refer them to someone in your practice to subspecialize or another of a colleague, a medical oncologist, radiation oncologist who is really on top of this. And I think that's really how we optimize care.
Tanya Dorff: Great. Thanks so much for being here today.
Neal Shore: My pleasure.