The Evolving Treatment Landscape of Low-grade Upper Tract Urothelial Carcinoma

EP. 2A: The Role of Kidney-sparing Treatment Approaches for Low-grade UTUC

In the second video interview of the series, Sandip M. Prasad, MD, MPhil, reflects on the role of radical nephroureterectomy and endoscopic resection in patients with high- or low-grade UTUC and highlights clinical experience with kidney-sparing approaches including the use of mitomycin gel.

I'm Dr. Sandip Prasad. I'm the surgical director of urological oncology at Atlantic Health System at Morristown Medical Center, [and] I'm practicing urologist at Garden State Urology in northern New Jersey. I'm one of 21 urologists in my group, and I specialize in bladder and upper tract urothelial cancer (UTUC).

The upper tract is really a different beast than the bladder in terms of the complexity of the anatomy. In many ways, that really limits our ability to treat the upper tract as effectively as we treat urothelial cancer in the bladder.

I think all patients [with] high-grade UTUC are still candidates for radical nephroureterectomy (RNU). Sometimes we’ll be giving these patients chemotherapy before or after their treatment, but I think all patients with high-grade upper tract disease were, and still should be, candidates for an RNU. Historically, many large low-grade tumors were also treated this way as well, because we just couldn’t reach those tumors with our scopes.

[For] tumors [that] we deem to be unresectable because we can’t get our instruments in there to treat them, these patients often went to an RNU, even if they had low-grade disease or even, to some degree, small-volume disease, because we didn’t really have a lot of tools to get to the tumor. I think, to some degree, that was really overtreatment of a disease [that] is generally low-grade with a pretty low metastatic potential simply because we could not ergonomically get in [to] treat a tumor.

Initially, you have to determine if a tumor is high grade or low grade to determine whether a kidney-sparing approach is appropriate. In the case of high-grade tumors, I believe very strongly that the entire kidney and ureter should be removed, so RNU remains the standard of care for that. I would also argue that, for low-grade disease, we should do everything we can to preserve the kidney.

From my perspective, there [are] 2 mainstays to kidney sparing that I think can be effective. The first is endoscopic resection, using a ureteroscope and the tools within that ureteroscope, to try to remove a tumor in its entirety. Even with improvements in instrumentation, we see that the recurrence rate for endoscopic resection is [such that] about two-thirds of patients will recur over the timeline of any study.

While I think endoscopic resection is a nice approach for the right tumor, again, if you have a small papillary tumor on a stalk, right at the ureteropelvic junction in the renal pelvis, you’ll be able to attack that tumor very effectively, I think, with a ureteroscope, and potentially clear that patient. However, that’s not how many tumors present in the upper tract. Many tumors are spilling like a carpet into different calyces, or they’re in places where we can’t easily reach them. I think the approach has become to use topical agents, and the product that’s approved right now for this is [mitomycin gel], which came out a couple of years ago, and I’ve had fairly significant experience using this product which has [overall] been positive. This provides the same ability of renal preservation with a success rate that’s well over 50%, and [it reaches] tumors that can’t be reached or treated [by ureteroscope because] you couldn’t get the ureteroscope in there to resect the tumor. The gel can really cover any surface, and it’s very easy to instill and can really reach any part of the kidney. That’s the really amazing part of this. For those unresectable tumors that I had mentioned earlier—those that unfortunately we would often do an RNU on because we could not remove the tumor or couldn’t reach it—[mitomycin gel] now allows us to treat those patients diffusely throughout the kidney, really in any location as long as we can get the gel there, which is basically every surface of the kidney. Kidney-sparing approaches should be the mainstay and should be the first-line [treatment] for low-grade upper tract disease now that we have a new tool in our armamentarium for this.

If I’ve determined that a patient has high-grade disease, I’m done: That patient will get an RNU. I don’t do anything else. If they have low-grade disease at that time, [if] it’s easily resectable and I can see that ergonomically, I will go ahead and try to do that [as] my first approach. Historically, I used to keep doing that no matter what because I didn’t have any other tools besides ureteroscopy.

Now, if I know that the tumor is not easily resectable, I won’t labor on because now I have [mitomycin gel], [which is], in my opinion, the primary strategy to treat upper tract disease that’s not easily resectable. Once I know that I have a low-grade tumor, I do my measurements to measure kidney volume so I know how much [mitomycin gel] to give, and then I take out the ureteroscope, and then I initially treat with [mitomycin gel]. [Mitomycin gel] is very easy to use. It can either be instilled [with] a retrograde approach, like the way we do a retrograde pyelogram, just running it through an existing catheter, or you could put in a nephrostomy tube in the patient and administer this in the office. So the technology is really quite nimble.

Mitomycin [gel is something that], as urologists, we’re all very familiar with in the bladder, but this is a different way of treating [LG UTUC]. It’s actually primary chemoablation, which is a really exciting way to think about treating tumors. The gel itself eradicates tumors, and that’s what was demonstrated in the clinical trial that got [mitomycin gel] its approval. They actually left tumors in place in the upper tract, put the gel in, and then looked back 3 months after the gel was administered, and those tumors were gone in a majority of patients. For those patients [who] were responders, there was a durable response in many patients that was up to a year, so I really believe this is a proof of principle that chemoablation works. What I like about this is it does not rely on my being able to see and eradicate all the tumor that’s there because it’s really hard to both see and eradicate tumors in the upper tract. [Mitomycin gel], because it covers every surface, to me is a more comprehensive way of treating LG UTUC.

Transcript has been edited for clarity.