Daniel Roberson: Thank you. Thanks for having me. Very excited to be here.
Ashish Kamat: So there's a lot of exciting things happening at the AUA and we have to pick and choose what we're going to feature here. You are talking about something that is very relevant today and the reason I bring that up is because clearly EV pembrolizumab is going to be very soon standard of care, if not already in many centers. As I've traveled across the globe, I've heard from surgeons in different parts of the world that the surgery after EV pembrolizumab is very hard. It's taxing. The tissue planes are all obliterated. And clearly, that's not been our experience and that doesn't seem to be the experience from the study. And of course, now you have a presentation here at AUA that addresses that in some way. So really, first off, very timely and if you would share with us your findings.
Daniel Roberson: Thanks for having us. It's an honor to present this work here at AUA and to talk about it a little bit further today. So as you highlighted, this all kind of came about, especially after EV-302 led to enfortumab vedotin/pembrolizumab being widely used in all patients with advanced urothelial carcinomas' first-line therapy and we were presented with a growing population of patients that fortunately had really robust and profound responses to therapy. And the question was, "Well, what do we do now? Are there benefits to consolidation and who are the right patients to offer consolidation to?" and I think we're still grappling with those questions. And I think quite honestly, our abstract and our work thus far has produced more questions than answers. But we have learned a lot and I think it's helped guide us to design some prospective work.
So to talk a little bit about the specific findings of our study, you mentioned about perioperative findings and certainly have heard from various, different surgeons that I've talked to and my mentors have talked to that, yeah, the surgery's different after this combination of drugs and this and that. Our experience has really not been that also. We really have not felt like surgery after this combination of drugs is any less safe or necessarily harder if you compare it to patients with locally advanced or regionally advanced urothelial carcinoma after, say, cisplatin therapy. Specifically from our findings, we found that whether it was a radical nephroureterectomy, which was about one-quarter of our sample population, or a radical cystectomy, both all complications, as well as high-grade complications, were very similar with contemporary series that report on these two operations. So we certainly didn't in our experience, again small experience, highly select patients, we did not feel like it was necessarily any more unsafe to proceed with surgery in these patients.
Ashish Kamat: And it's encouraging to see that in the real-world setting, right? Because again, from the trial, if you look at the data from the trials itself, clearly they don't capture perioperative complications as part of the trial design because it's a chemo complication detection.
Daniel Roberson: Sure.
Ashish Kamat: But if you kind of extrapolate from the patients who actually reached surgery, the patients who had negative margins, which is always a good surrogate for the adequacy of surgery or the difficulty of surgery, the negative margin rate was a little bit higher actually in the EV pembrolizumab group. Now obviously that's because the drug works better, but it wasn't lower. So at least that's a surrogate for the fact that the surgery itself, even though like your mentors have told you, and I have actually heard from people saying the surgery is much more difficult, it really isn't. It's a little different, maybe a little different reaction around the tissue planes, but not. When you look at your series though, now trying to look a little deeper into what you found, were there any clues as to maybe the stage of the patient that started out with disease, maybe more bulky tumors when they responded? Did they have prolonged operative times or EBL or any clues there at all? I know it's small numbers, but any clues for the audience to take?
Daniel Roberson: Yeah, good question. I think that if there were any clues, we did find that some of the upper tracts maybe didn't respond as well and they had radiographic and residual disease going into surgery, and I think there was a little bit higher EBL, longer operative times with some of those patients. Again, even talking about small sample size, looking at the upper tract patients in our studies, even smaller sample size, but I think that was something that we did see. Aside from that, not really. And with both approaches to surgery, minimally invasive or open, we found that it was surgeon preference as to how they were going to approach surgery, but we found that surgeons did not need to change their usual approach to these operations going into them.
Ashish Kamat: Yeah, and I think in closing really, the message to the community is that this paradigm is here to stay. It is a new paradigm for patients and the surgery is not something that anyone should worry about having changed, right? Whether or not we need to offer it, "Can we spare bladders?" that's a whole different question. But the surgery, when done by people that know what they're doing, is safe and effective. So thank you so much for presenting this and doing the study and congratulations.
Daniel Roberson: Thank you. Thank you so much for taking the time to talk today.