Antegrade Administration of Reverse Thermal Mitomycin Gel for Primary Chemoablation of Upper Tract Urothelial Carcinoma via Percutaneous Nephrostomy Tube - Katie Murray

September 29, 2022

Katie Murray joins Alicia Morgans to discuss reverse thermal mitomycin (JEMLYTO®) for primary chemoablation of upper tract urothelial carcinoma (UTUC) via a percutaneous nephrostomy tube. Based on results from the pivotal OLYMPUS trial, JELMYTO® is currently approved for low-grade UTUC. Dr. Murray speaks to two different methods of administration of the mitomycin gel that was allowed in this trial, their adverse events, and their safety profiles. The two methods were cystoscopy retrograde administration and a nephrostomy tube directly into the kidney.  In the multi-institutional real-world experience of antegrade administration of reverse thermal Mitomycin Gel for primary chemoablation of UTUC via percutaneous nephrostomy tube, the authors concluded that mitomycin gel administered through an antegrade PCNT for UTUC offers a favorable side effect profile with a low rate of ureteral stenosis with no requirement for general anesthesia or utilization of operating room resources.


Katie S. Murray, DO, MS, FACS, Assistant Professor of Urologic Oncology, Medical Director-Ellis Fischel Cancer Center, University of Missouri Health Care, Columbia, Missouri

Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts

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Alicia Morgans: Hi. I'm so excited to be at AUA 2022 talking today with Dr. Katie Murray. Thank you so much for joining me.

Katie Murray: Great. Thank you.

Alicia Morgans: Wonderful. So I wanted to talk with you about some really interesting advances. And actually, something that you've been involved with as the person who's performed the first of these procedures, I'd love to talk about the mitomycin gel that we're using now in patients who have upper track urothelial carcinoma, low grade, and specifically kind of drill into the concept of percutaneous nephrostomy administration of this gel. First, can you tell us a little bit about this disease state and how we've dealt with it over time?

Katie Murray: Yeah. So low-grade upper tract urothelial cell, the standard of care for upper tract disease would be a nephroureterectomy. We know that is an invasive procedure that may not be necessary, especially for those patients with low-grade disease. Recurrence is a problem but progression not as much. And so historically we've also done lots of endoscopic ablations. What does that mean? That means a ureteroscopy, like we would do for somebody with kidney stones, identify these tumors and use a laser to try to get rid of the tumors. Recurrence rates push 65% with that kind of procedure. So it's very exciting that in 2020 first time we have a chemo ablative technique with mitomycin gel for this specific indication, low-grade upper tract urothelial cell. So approved by the FDA, 2020 was with the OLYMPUS trial, 71 patients single-arm trial, that shows a really good, complete response for patients at their first evaluation of this disease.

Alicia Morgans: So, what was interesting about that trial though, and you just shared this with me before we started talking, is that the administration of the mitomycin gel was allowed in two different ways. And I think in every case in this trial, it was administered by weekly cystoscopy and administered surgically, essentially. So can you describe the two options and really what happened in the trial and where you went in terms of your first administration?

Katie Murray: Yeah. So in the trial, I always say it was treating physician's choice. So a cystoscopy with what we call a retrograde administration, so a catheter that goes into the ureteral orifice up into the kidney. This is instilled as a chilled liquid, goes in as a liquid form, and as it hits body temperature, it forms into this gel that conforms to the renal pelvis, stays there four to six hours before it goes back to liquid and drains itself out. So again, in the trial, every single person had this administered via that cystoscopy retrograde approach. Now that can be done in a clinic setting. Oftentimes it's done in an operating room setting. And a reminder that this is a therapy that we instill once a week for six weeks. That's potentially the lots of procedures potential with anesthesia for those individuals.

So I had the luxury in my population of the very first patient that came to see me to be treated with mitomycin gel, a great candidate, low grade, upper tract urothelial. And he said to me, "Yeah, I don't want to lose my kidney. This seems like a great idea, but I also had a lot of cystoscopies in my life and I don't want to do that six times in a row. Can't you just put it directly into my kidney?" And so I went back and we looked and we said, "Yeah, that wasn't a way that we could do it in the trial." And so we administered that. So we put a nephrostomy tube in, directly into the kidney, very cautiously so that we don't put it into a location where there is urothelial cell cancer. Of course that's always a concern. And then they come back and we start the installations the following week once a week for six weeks. One week after that I remove the tube. So they have this tube in about eight weeks in total throughout the treatment of the disease.

Alicia Morgans: But I think it's so interesting. And I didn't understand as you first described it because I don't do these types of procedures, but really this is as your patient described it almost a port, like a chemotherapy port, that is accessed just once a week, otherwise capped and adherent to the body taped down so that the infection rate is actually very low because it's really not accessed continuously and is a pretty nice option for a patient to avoid that weekly instrumentation.

Katie Murray: Absolutely. I think that's true. And for urologists, we're familiar with nephrostomy tubes. We place those and our patients have them. But one thing is so many of those patients have it hooked up to a urinary drainage bag. This is not. It doesn't have to be draining all the time. And so it is just kind of plugged and bandaged up to their back. They wear their clothes over it. Nobody notices it. And like you said, my patient, he says, "Oh yeah, that's my port." And chemo ports are familiar with patients. It's a very familiar, common thing.

Alicia Morgans: It's so interesting. So one thing that I think would be so interesting is actually doing a study where you could look at patient-reported outcomes between the two administration methods. Is this something that you and the team are considering?

Katie Murray: Yeah. So we're actually in theq

Alicia Morgans: It is so interesting. Now just to follow up on one thing that you mentioned, adverse events, how did the adverse events of this administration, at least in your real-world population, compare to the weekly procedural administration?

Katie Murray: So, what I have is data from the trial. And so in the trial, close to 50% of patients had some form of a ureteral stricture hydronephrosis or worry of narrowing down of the ureter. And then I know from the data that we have 26 patients now having it done through a nephrostomy tube, that that rate is nearly in half. So we're not looking at the same patients and comparing the trial to what we have now in real world. But absolutely something from another standpoint, patient-reported outcomes, and maybe we can impact and decrease those adverse events by thinking outside the box in a different way of administration.

Alicia Morgans: It is really interesting. Well, I commend you and your team for really moving this approach forward. It wasn't done in the clinical trial, though was an option. So really exciting that you and the team realized that this was possible and took the next steps to treat a patient. As you think about the message to patients and to clinicians who are considering use of the mitomycin gel, what would your message be?

Katie Murray: I think that it's very rare in surgical times that we have something that changes what we actually do. And this is a disease that we've never had anything for, low grade, upper tract urothelials, so you got to know about it. You've got to talk to your patients about it and look at the tolerability, and let's try to save kidneys when it's safe and when we can.

Alicia Morgans: I think your patients will appreciate you for that. So thank you so much for your time and your expertise.

Katie Murray: Thank you.

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