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Sam Chang: Hello everyone, my name is Sam Chang. I'm a Urologist in Nashville, Tennessee, and I work at Vanderbilt, and I am quite fortunate today to be joined with Dr. Katie Murray. Dr. Murray is an Assistant Professor in The Division of Urology at The University of Missouri, and I've had the privilege and honor of knowing her ever since she was a medical student applying for urology. We were unable to capture her here at Vanderbilt and she has gone on and done fantastic things. Finished a fellowship at Memorial Sloan Kettering, and is now really leading the division in terms of oncology and future roles, and a superstar, for sure. So we've asked Katie actually to give us kind of a nuts and bolts presentation today on how she treats upper tract disease, and specifically, low-grade upper tract disease, as the treatment for this disease process has definitely evolved over time. So Katie, thank you again for giving us this presentation, and we look forward to seeing how you do things.

Katie Murray: Great. Thanks so much. Thanks for having me. So we titled this, how do I now treat it, in comparison to maybe how we did in the past. So again, thank you.

So I think the most important thing for us to think about when we are just thinking about upper tract disease is risk stratifying this. We always talk low-grade, high-grade, and things like that, but really to be thinking about who are the patients who are low-risk, who are the patients who are high-risk. So today, we are really going to focus on this left-hand side where it is low-grade upper tract disease. So these are the patients with unifocal disease, small tumors, above the UPJ, low-grade or negative cytology, UR confirmed with biopsy that is low-grade, and when you look at their axial imaging, you do not see any evidence of invasiveness of disease. So that is really the side of this that we are looking at today.

So just with every disease that we treat, treatment needs to be based on our risk. Low-risk should not equal aggressive interventions. So what is our goal? Not equaling aggressive interventions, meaning we are saving nephrons. Let's don't run and take out all of these kidneys. We are all urologists, we're surgeons, we can do that, that is in our nature, but let's look beyond, let's treat the disease that needs to be treated.

So why, when, and how. Why do you not want to take out the whole kidney? Why can you spare these? Well, one thing, and we talk about this all the time with our patients with urothelial cells, we talk about disease recurrence. We talk about the metachronous disease. We talk about what if years down the road, something happens in your other kidney. Your other comorbidities, what if you have diabetes, what if you have hypertension, what if these other things start to really impact your kidney and we've taken out a kidney for low-grade upper tract disease? What if the patient needs future chemotherapy, not even for urothelial cells, what if they need chemotherapeutics for something else and we can never go back in time and get those nephrons back that we took out for the low-grade upper tract? So that's the why. Pretty simple. Taking out kidneys impacts renal function.

When? I say the when is pretty easy, the when is always, if it's possible. This is what we sit and we talk about with all of our patients every day. We are weighing out these risks and benefits. We're discussing with them the why, and that why tells us that the when is all the time. How do we do this? How do we not do nephroureterectomies on patients with low-risk upper tract disease? We do that endoscopically with endoscopic ablations, and now, in 2021, we do that with chemoablation.

So ureteroscopic ablations. I think there are a few points that are so important for us to remember or principles that I think about when I treat somebody in saving nephrons by doing ureteroscopic ablations. If I plane, or look at the contralateral kidney, I know which one I'm after. I always do it first and I use separate disposables if I'm going to do that. If you're using a ureteral catheter, if you're using ureteral access sheaths, et cetera, I do think it's important to not cross those over. I do use a ureteral access sheath if I'm going to do an ablation above the UPJ so that I am not seeding down to the bladder. I do think it's so important to do a biopsy. You can do that in whatever way that works for you. We all know this sounds simple, you always need pathology, but doing an upper tract biopsy is not always simple. Using biopsy forceps, sometimes a thicker nitinol basket that would be used for stones can be advantageous.

Selective cytologies from that area. Basically, this is ruling out that high-risk disease. You've got to make sure that you are not dealing with more invasive disease. I also like to use an immediate post-ablation intravesical chemotherapeutic. So my go-to is intravesical gemcitabine immediately after ablation. So very similar to treating a patient with low-grade disease of the bladder, within the first 24 hours, in the recovery room with a catheter for one hour. It can require many trips to the operating room, so I think that we need to make sure we explain that to our patients. Larger tumors often require staged approaches where you de-bulk the tumor as much as possible, and then come back a couple of weeks later.

And hen excellent documentation, right. We've all been told this over and over, and for so many reasons, documentation is important, but I think with some of the options we have today, that becomes even more important. So documenting your size and location of tumors as well as you can, and doing volumetric measurements of the upper collecting system above the UPJ. That becomes important because when we start talking about chemoablatives, these measurements — how much volume does a kidney hold — becomes important for dosing.

So the next step on the list of ways to spare kidneys is to do chemoablation. In today's world, since 2020, we have the approval of Jelmyto, which is a novel reverse thermal hydrogel technology that contains chemotherapeutic mitomycin. This is very standard for what we're used to as urologists. It is completed in an induction six-week course plus or minus a maintenance therapy. Again, the dosage is dependent upon the volume of the collecting system, so it's four milligrams per milliliter. How much does a patient's renal pelvis and calyceal system hold, right? And that is the reason for all of this excellent documentation at the time that you are doing ureteroscopy on patients with upper tract disease. Then I think the most important thing is ensuring that your patient meets that low-risk stratification, doing that biopsy, doing those cytologies, and making sure that you have some axial imaging.

So chemoablation, why do I now choose this option? Which has been my go-to for the past year. I think there are some advantages; advantages to us as urologists, advantages to our patients. It can be done in multiple settings, it can be done in your clinic, it can be done in an operating room setting. Again, it's very familiar to us. We are well-versed in this weekly installation six times. We can explain that to patients, we understand that. Side effects are quite tolerable. It takes out this concern that I always have when you are doing ablations, as far as kidney pressures and how much irrigation you are using during ablations. You get and the patient gets results in a short time period. Six weeks of an installation, and then about four to six weeks after that you are looking inside that kidney and you are getting some results for them. It can avoid the bleeding that you may have with ablations, it can avoid ureteral stents, and it can avoid anesthetics recurrently if that's what you choose to do.

And that is the conclusion of my slides. Again, just thanks to Dr. Chang and UroToday for this opportunity,

Sam Chang: Perfect, Katie, because now that presentation gets us to the real meat of the matter of, okay, what do we do every day? So in looking at your slides, a couple of things that really jumped out to me that I think are important. One, the documentation, because I think you are really right, the exact location of tumors, their size, their nature, all those things. Is there a certain template that you follow? Do you always say the upper pole calyx looks like this, the interpolar ... Is there a certain way that you kind of organize and codify how you describe what you see with ureteroscopy?

Katie Murray: So I still do the typical template in dictating my way through an operation, but I make notes and I have a fill-in-the-blank where I do talk about upper pole, mid pole, lower pole. And before that actually is describing it, because not every patient has an upper pole, a mid pole, a lower pole, and it's not that simple. So I always do retrograde. I'm measuring out those volumes in case I need it in the future, because I may do a chemoablation, so I've added that to my template of what I run through.

Sam Chang: Let's stop there. So what's the average volume then of a renal pelvis in terms of what you may be expecting to put in with a jelmyto. Is it a few ccs, 9 ccs? We are starting this process, so is there a certain range that you found that seems to work the best?

Katie Murray: Good question. I think a majority of my patients have fallen somewhere between six ccs to about nine or 10. Eight has been a very common dose, eight milliliters that I've used. I have had one patient who was up to like 12 milliliters from the UPJ up, and she just had a really, not really blown out, but just had a really capacious UPJ that was there.

Sam Chang: So as you do that, you've described it, you've talked about the nitinol basket or biopsy, and I love all those. I've definitely started using baskets for these papillary tumors. Any tricks regarding — I'll use the word carpeting — like there will be lesions that are not papillary or do not have a large stock, but basically are carpeting a calyx or part of the renal pelvis, any tricks regarding how you biopsy those areas?

Katie Murray: I don't have any wonderful tricks. Those are the toughest ones to do, a basket doesn't really fall in. I always use a ureteral access sheath, so you can use the [crosstalk 00:12:31] if you have a sheath in, and I do think it's a little bit better in getting a bigger chunk.

Sam Chang: So then as you have talked about measuring volumes and giving the chemoablative agent, do you try to rid all of the tumors that you can see? In other words, endoscopically, laser, or biopsy remove as much as you can before giving this medication? Or do you know that there are times where, okay, I'm not going to be able to get to this lower pole and well, just how do you determine how much you are aggressively treating endoscopically versus the chemoablation or the combination? How do you work that out?

Katie Murray: I think that's a great question, and this is where it, I think, is difficult for us as urologists. We know adjuvant therapy, and this is a chemoablative, and it's different, but I do kind of exactly what you mentioned. If it is a lesion that is easily ablatable for me — upper pole, mid pole — I'm not going to struggle, I'm not going to worry about if I pop in the laser and get some bleeding that then I'm stuck and I can't get out of, i.e. a lower pole, that I can't reach then later, I will ablate those upper pole spots, those mid pole spots. The lower pole, just because of that angle, and you get into bleeding and you can't get something down, I often won't ablate those, and I will leave those up to the jelmyto.

When I first did it, I did it very much what we are used to as adjuvant therapy. I tried to debulk them completely. I recently had a patient, and she said, "I don't want any of those lasers anymore. Don't do that. That hurts." I'm not sure that's true, and so I did it as a true, I went in, I saw it, I biopsied it, diagnosed it, and left it alone, no lasering, and then I did the chemoablation and was pleased with the results. So I think it's a combination.

I think the important thing to note also is this jelmyto is not going to ablate big, bulky tumors. Tumors are not going to disappear with that. It was indicated in the trial for patients that had upper tract tumors less than 1.5 centimeters. Measuring in the upper tract is a whole other beast. How we determine what that 1.5 centimeter is, I could say one thing and you look at it and tell me something different. We don't have a good way to do that, but I do think it has to be to your judgment. I've had people with larger tumors, I do try to ablate them down to that smaller size, get down to the base of that tumor before giving the jelmyto.

Sam Chang: So then the last question, that technically with these tumors that you have diagnosed endoscopically that meet the criteria you set up in terms of risk stratification for low-risk tumors, that you are trying to save the nephrons, which I think is a point that everyone wants to emphasize, is now how are you placing the medication? Are you putting a small percutaneous tube in? Are you doing the ureteral catheterization? What have you found the most effective and why?

Katie Murray: So I've done it both ways, and it's approved to do it through a nephrostomy tube as well as a five or seven French ureteral catheter via cystoscopy, with or without anesthesia on either way. A majority of the patients I've treated have been using the percutaneous approach, which also brings up the point of that documentation of where your tumors are. We also know urothelial cell, and we know that it can grow anywhere it wants to grow. So everybody has a fear of putting a perc into a kidney with urothelial cell cancer. Very fair worry. But if you have that documented of where ... If there's a tumor in a calyx, which calyx is it in? Don't perc right into that. Interventional radiology puts nephrostomy tubes in for me, in my practice, so it takes good communication with them. I just had one yesterday and they said, "Katie, you were really strict and told us you had to have an upper pole. Is that true?" He texted me and I said, "That's true. If you can't do upper pole, don't do it."

Sam Chang: I think that's a key point, avoiding access then into a calyx that you know has disease to avoid that. I said it was the last question, but that's a little bit of a fib. So then logistically, are the patients prone, are they on their side? What's the best way to try to fill that pelvis up then with a chemoablative agent?

Katie Murray: Yeah. So I've just been doing it in the supine, location in the clinic, and it's one of those things, once it happens, nephrostomy tube gets placed, one week later is what I've been waiting and that's just that week to allow that tract to heal, and it works into my clinic schedule, they know that it's one week later, the patient comes in and I'll do the installation. Sometimes the nurse will do it with me now that we've gotten the hang of it. But supine.

Sam Chang: Fantastic. So that whole process, we are talking a few minutes then?

Katie Murray: Yes.

Sam Chang: Great. Well, Katie, thank you so much for your experience and insights. I think we are all excited about the continued attempt to, just as you say, treat what we need to treat and not over-treat. I think the insights, and everyday experiences you have presented to us, are going to be really, really helpful. So thanks for taking the time and showing us a little bit about your practice as well.

Katie Murray: Great. Thank you.

Sam Chang: Take care.