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Zach Klaassen: Hi, my name is Dr. Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. I am delighted to be joined for this UroToday discussion with Dr. Dan Saltzstein, who is the medical director of research and the director of Advanced Prostate Cancer at Urology San Antonio. Dr. Saltzstein, thanks so much for joining us today.

Daniel Saltzstein: Yeah, Zach, thanks for inviting me. Appreciate it.

Zach Klaassen: So, we are doing a series, and we're delighted to have you speaking about, basically, the collaboration around triplet therapy for metastatic hormone-sensitive prostate cancer, specifically docetaxel, ADT, and NUBEQA. And so, I guess, to start off with our listeners, how do you collaborate with your medical oncology team with these patients, specifically?

Daniel Saltzstein: Well, we have a very unique setup in San Antonio. Approximately 4 to 5 years ago, as we saw some of the treatment modalities moving into an earlier space, we started doing a lot of clinical trials with a medical oncologist. That medical oncologist is now part of Urology San Antonio, so we're all housed under one roof, per se. So, it makes it very easy for me to introduce triplet therapy or treatment intensification, because I work hand in hand with my medical oncologist. I'm not fighting some of the other challenges that might be out there in the community at this point in time.

Zach Klaassen: For sure. Maybe you have a specific patient in mind, what sort of patients are you looking for when you're identifying, perhaps, patients that may benefit from collaboration and from triplet therapy?

Daniel Saltzstein: I think if you look at the trials that are out there, it's that high-volume, I would say high-risk, patient, and I use the term chemo-fit. Again, I'm not going to probably take the 88-year-old guy that's got multiple comorbidities, even though he has got high-volume disease. I'm looking for someone that meets those criteria, as far as a patient that I would feel is appropriate for triplet therapy.

Zach Klaassen: That's great. So, basically, that younger patient, perhaps PSA is over 100, high-volume disease, those are the guys that you're going to target for collaborating with your medical oncology team?

Daniel Saltzstein: Absolutely, absolutely. Those are the guys we're looking for at this point in time.

Zach Klaassen: I think, too, when I explained to the patients, and correct me if you think the same way, but when you see somebody, now that the NCCN guidelines have done away with chemo plus ADT as a standard of care, and are really recommending triplet, those are the guys that being chemo-fit is really the yes or no question when you're looking at these patients, right?

Daniel Saltzstein: Yeah, I mean, it's interesting how we've gone from CHAARTED and STAMPEDE, and that was the first kid on the block, and we were co-managing these patients, and now that's been replaced by triplet therapy. I think the data have proven it out, that the overall survival, the delay to a metastatic castrate-resistant state, that if you can find a healthy person that you would've given chemotherapy to, that is the perfect patient for triplet therapy at this time.

Zach Klaassen: Absolutely. When you guys identify patients, logistically, who's giving what? Is your medical oncology team only just giving the chemo? Are you doing everything else? Do they see them first? Do you see them first? How does it work from a logistical standpoint?

Daniel Saltzstein: Well, it's unique in how they present, but most of the time, these guys are still presenting in our office, most of them are that de novo, never had any kind of treatment for prostate cancer. They walk in the door with that PSA of 115 and then you work them up and you find out that they've got metastatic disease, whether it's nodal, bony, or visceral disease, that kind of thing. In our office, it's usually the urologists who are managing ADT and also managing that androgen receptor signaling inhibitor, annot a hormonal agent. And then, once we've established that, then our medical oncologist comes in and does the chemotherapy.

Zach Klaassen: When you guys have that initial consultation, what sort of conversation are you having with them regarding the chemo? Because patients hear chemo and they think this is going to be forever, they think they're dying of disease, and that it's six cycles with a hard stop. How do you approach that conversation with them?

Daniel Saltzstein: Again, you and I both have experience; it used to be a lot more cycles and a lot later on when they weren't chemo-fit, so it's a little bit easier of a conversation, especially when you say six cycles, very well tolerated, you might be given growth factors with it to prevent any of the neutropenic sepsis, things like that. And when you sit down and look at them in the eye and tell them, "Hey, this is our best chance for you to hit it early on," I think they agree and they pursue that option.

Zach Klaassen: From a broader sense in terms of collaboration between medical oncology and urology, as we move into the radioligand therapy era and certainly triplet therapy for prostate cancer, what's your message to the listeners with regards to that collaboration? Because it sounds like you guys have a great setup under one house. You guys work together in partnership a lot.

Daniel Saltzstein: Yeah. I think that the trend in urology, whether it's prostate cancer, kidney cancer, or bladder cancers, too, whether it's PARP inhibitors, whether it's dual therapy, whether it's radioligand therapy, whether it's the immuno-oncologics, you really need a close collaboration with a medical oncologist who has a lot of GU experience, whether it's neoadjuvant before a cystectomy. That's kind of how it started with us and then through clinical trials and going forward. So, I strongly recommend it.

You mentioned radioligand therapy. We've done about 20 patients already in San Antonio, mainly in the pre-chemo space because of a clinical trial we've now had, because we already have patients exposed to chemo who are getting PLUVICTO radioligand in therapy afterwards. So, I think it allows you to keep that patient, I hate to say it, from diagnosis to death, right? They're under your auspices, so to speak.

Zach Klaassen: No, that's great. I think when we look at, maybe there's some listeners out there that either are maybe afraid of sharing patients, maybe there's some barriers to sharing patients. What's your message to maybe a urologist that wants to just keep the patient to themselves and maybe doesn't either have the setup for a collaboration or doesn't necessarily want one? How would you sort of message those folks that are maybe a little hesitant?

Daniel Saltzstein: Again, I understand the hesitancy. I think there's some urologists who feel like they might lose the patient. I understand that. And there are a lot of hurdles to getting to the point, a lot of referral lines, and there's the politics, of getting your partners to feel comfortable, so you're not going to get woken up in the middle of the night with neutropenic sepsis, et cetera, and then San Antonio's model might not fit everybody else. I know that Nashville, they've found a medical oncologist who's very experienced in GU oncology. They have a tumor board once a month. They know that when they send a patient there, the patient's also coming back, so they can manage the ADT and NUBEQA, or however it works, and then they're getting all their docs that want to be involved on those tumor boards. So, I think you've got to figure out your own community and figure out what's best for you, and then institute that because it's the best thing for the patient, and that's what we need, right?

Zach Klaassen: That's well said. I think you nailed it. There are more sets of eyes, and everybody's got their specific role. I think that's a great takeaway.

Daniel Saltzstein: Right, absolutely.

Zach Klaassen: When you're talking to patients about triplet therapy, specific to the ARASENS trial, are there any nuances in the trial, whether it's time to CRPC, some of these really deep PSA responses? What sort of nuances do you use in somebody who's maybe thinking about it, not quite there yet?

Daniel Saltzstein: I kind of go over what I call the three Ps. It's about prolonging overall survival, the delay to castrate resistance, and the most important thing is about preserving the quality of life. If you just tell them upfront that that's your goals, "This is why we're going to do it, and this is what the trials have shown," they usually will follow your lead and do it. I think the beauty is that NUBEQA is a very, very well-tolerated drug without a lot of drug-drug interaction, and so you're not adding, in my opinion, a lot of toxicity when you do the triplet therapy.

Zach Klaassen: That's great. Any last take-home messages? Maybe something we haven't hit on yet you want to share with our listeners?

Daniel Saltzstein: I don't know if I have anything really profound to say other than our specialty is moving to the point where we need to engage, whether it's with radiation oncology, whether it's with medical oncology, or with radiologists with all the PET imaging. We have a navigator that helps us navigate these patients and get them to the right doctor at the right time. So, the take-home message is that it takes more than just the urologist to manage these patients, so we should be part of a multidisciplinary team.

Zach Klaassen: Well said. Dan, thanks so much for your time. We really appreciate your expertise today.

Daniel Saltzstein: Thanks, Zach. Appreciate it. You have a great day.