Effective Techniques for Nephron Sparing, Mitomycin Gel for UTUC

Katie S. Murray, DO, NYU Grossman School of Medicine, and David Ambinder, MD, Urology Resident, New York Medical College/Westchester Medical Center, highlight some of the latest research that suggests which patients are ideal candidates for nephron sparing management for upper tract disease, as well as candidates for mitomycin gel.

Dr. Ambinder: We’re welcome to have Dr. Murray here, and obviously you’re a big name when it comes to upper tract urothelial carcinoma. You’ve been involved in some of the critical trials and some of that’s been introduced in the latest guidelines. Just by a way of introducing us to the topic, can you tell us in the guidelines, who are the ideal candidates for kidney sparing management of upper tract disease?

Dr. Murray: Yeah, thanks so much for having me. I think, first of all, it’s very exciting that the AUA came out in 2023 with guidelines for upper tract urothelial carcinoma. We’ve never had those before. If you look at the guidelines, the way that it is described to us is very familiar wording to us as urologist. It talks about high risk and low risk, and even within those, they give favorable and unfavorable. So, not quite as complicated as some of the others in prostate cancer knowledge, just high, low, and then favorable and unfavorable for each of those. That’s important to understand and really look at what that chart looks like to determine what the best treatment is for people. Those patients that fall in that low risk categorization are the ones that you’re really going to think about sparing a kidney, or it’s the safest possibility to spare a kidney.

These are our patients who have a negative urinary cytology. You’ve gotten axial imaging on, and there’s no appearance of any hydronephrosis or major obstructive symptoms. And then when you do ureteroscopic examination and do a biopsy, whether that be with a basket or biopsy forcep of some sort, ureteroscopically, that it comes back as a low grade papillary tumor. Again, like I said, that cytology is negative as well, so negative for high grade disease, and then based on tumor focality, right? Is it a solitary unifocal tumor? Is it multifocal? That vocality is really what determines favorable versus unfavorable in that low risk categorization. I would push you to say that’s really the candidate that low risk of people for kidney sparing or nephron sparing surgery. There are some suggestions that patients with very unifocal disease with high grade disease who are not great candidates for nephroureterectomy, you can also consider kidney sparing approaches.

Dr Ambinder: What is the basis for it? What does the data show us in terms of survival? In terms of outcomes?

Dr. Murray: Kidney sparing or nephron sparing is not anything new. Organ sparing is something that we do in so many of the diseases and treatments that we have. It’s not new, meaning we’ve been doing endoscopic ablations or percutaneous resections for upper tract urothelial carcinoma for quite some time. But, now we have a guideline to guide us to fall back on to say, “which person should we be doing this on, and which one should we not?” From an oncologic standpoint, it has been deemed quite safe as far as overall survival, as well as cancer specific survival outcomes.

Dr. Ambinder: You mentioned some of the different techniques that we use in managing nephron sparing and in managing upper tract with nephron sparing approaches. Can you touch on what we were doing prior to the OLYMPUS trial? Obviously, it is still considered standard of care, but what are some of the things that we were using for adjuvant installation?

Dr. Murray: I think this concept of doing an ablation or doing a resection for urothelial carcinoma followed by an adjuvant therapy is something very familiar to us. We do it in bladder cancer all the time, so we’ve tried to repeat that over the years for upper tract cancer. We do a large endoscopic ablation with a laser and theoretically place a ureteral stent and then use aqueous chemotherapy into the bladder, trying to get that flush back up into the kidney. There have been trials over the years looking at aqueous chemotherapy through nephrostomy tubes. Unfortunately, the dwell time of some of those things have just not been good enough to have any real impact on outcomes in the adjuvant setting or even in the chemo ablation setting, which is where in 2020 when the OLYMPUS trial comes out. It is a game changer for these low risk patients as it adds something else to our armamentarium for upper tract disease.

Dr. Ambinder: And what is that?

Dr. Murray: You know this and others know it, but the OLYMPUS trial got mitomycin hydrogel technology approved by the FDA, and it’s very strictly approved for upper tract tumors that fall in that low risk. Now, I will say in that a AUA guideline, low risk categorization, a favorable or unfavorable disease, and I think that that’s really important. It can be used as a chemo ablative, so in place of doing endoscopic ablations, but also can be used as an adjunct to what we’re already doing, right? We’re already doing ureteroscopy, already doing these laser ablations, and then we just add this mitomycin gel on top of it.

Dr. Ambinder: Can you tell us how it works? What does it look like in terms of consistency prior to instilling it and what does it look like after?

Dr. Murray: I can tell you the basics of what it is. Obviously, the technologies is pretty cool idea, but when it comes to you from pharmacy, it comes and then you put it on an ice and it goes on ice for about 10 minutes. And what that does is it creates it into a liquid consistency, so completely aqueous consistency that allows you to instill it into the upper urinary tract into a structure like that. When it hits that body temperature and it starts to warm up, it turns into the semi-solid gel. I’ve heard people describe it as a jello type of thing or a jelly, but it really is this semi-solid gel, and it kind of comes in this bluish purple color. The cool thing about that is to think that it can meet all of those little crevices of the upper urinary tract of the calyces that sometimes are hard to get to ureteroscopically.

Dr. Ambinder: In terms of access, that’s always a question people have is retrograde versus antegrade. What do you feel and what are your thoughts on that?

Dr. Murray: The exciting part is, as I always tell people, it can be used along with ablations. It can be used with those things, but so there’s definitely the patients out there for it. You can choose to instill it any way you want or any way the patient wants and in any physical location they want. It can be done in an ambulatory care center, it can be done in the operating room, it can be done in your office. It can be done via ureteral catheter. So, a cystoscopy with ureteral catheterization with a five to seven French catheter where it’s injected retrograde or via antegrade nephrostomy tube in any office setting as well. It’s really versatile to where you can do it in several different locations and physically, however you want to put it in.

View their further remarks on Mitomycin Gel Adverse Events and Administration in the Community Setting.