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

EP. 3A: Mitomycin Gel for the Treatment of Low-grade Upper Tract Urothelial Carcinoma

In the third interview of the series, Sam S. Chang, MD, MBA, from the Vanderbilt University Medical Center shares key insights into the role of mitomycin gel as a kidney-sparing approach to the treatment of low-grade upper tract urothelial carcinoma.


For LG UTUC, our treatment options [have ranged] from removing the entire kidney and ureter to doing endoscopic laser treatments, fulguration, [or] biopsy removal, where … tumors would return. And they can return quickly: in a few months, within 6 months, [or] within a year. The impressive thing about this agent is [its] ability to not only treat tumors that are already there and obliterate the tumor, but [it can also] help prevent them from coming back. The data regarding long-term 1-year responses are quite good.

At this point, we have a significant treatment alternative where we never had one before. We're able to give a medication that spares the kidney [and] decreases the number of required therapies, treatments, or invasive procedures. As [a] result, you have a [noteworthy] change in terms of being able to treat these patients in a way that avoids loss of the kidney [and] loss of kidney function but, at the same time, decreases the number of interventions required.

This is a gel that starts off as a very thick liquid. It's kept at a cold temperature, and, once it reaches body temperature, it then solidifies. By going in as a thick liquid, it's able to interconnect within the geography or the layout of the kidney itself. As it approaches body temperature, it solidifies, and, as a result, [it] is able to stay on the kidney for a period of time.

We have utilized a technique that more recently [was] described as putting a small nephrostomy tube into the kidney directly and then injecting the medication in the clinic without requiring any type of anesthesia. This has gone quite well. Patients are tolerating it well, and we have had good responses.

These aren't very, very common patients. At this point, we really follow the FDA [United States Food and Drug Administration] indication for these patients. This is [for] low-grade disease, not high-grade disease. This is [for] disease in the renal pelvis as opposed to any lower [area] within the upper tract, such as the ureter. For those patients [who] fit the criteria, I'd say [that] more than half have proceeded to receive this medication in the antegrade route in an attempt to treat the disease and prevent recurrence.

I don't know if we're attempting to basically use it simultaneously [with resection] like we would for those patients [who] we treat with chemotherapy agents in the bladder. The big advantage of using this following treatment with laser ablation or with biopsy and removal is the real decrease in recurrence rates. As [a] result, by decreasing that recurrence rate, we then decrease the number of interventions required.

These [are] clearly those patients [who] have any degree of renal dysfunction or who have the bilateral disease where radical nephroureterectomy (RNU) or loss of nephrons would significantly impact the quality of life for those patients. [For] patients with any type of renal dysfunction or bilateral disease, who tend to have lower-volume disease, [we will] attempt to avoid RNU. Those are patients [who] are likely to get benefit from using the mitomycin gel. The question is whether we should be expanding the treatment [to include] those patients [with] smaller high-grade lesions or, perhaps … patients with tumors in the proximal ureter. We haven't yet expanded our indications at this time, but, clearly, we think those patients are very good candidates to proceed with the mitomycin gel.

You clearly have a very tight indication given by the FDA in terms of when this medication can be used. It's for low-grade tumors within the renal pelvis, so there are issues with accurately diagnosing patients. [Accurate] sampling [of] these tumors can be difficult, so, as a result, we are still quite careful with the indications at this point. We may be undertreating some patients, [and] we may be overtreating some patients. Clearly, being able to follow the FDA indication is something that can really limit who we can treat and how we treat [them], but, for patients, when you consider the possibility of having a significant surgery where half their kidney function (at least) is removed with an RNU, it is something that can be quite life-altering.

We’re avoiding a procedure that can lead straight to dialysis. If you have a solitary kidney, and we don't have good treatment options, we're talking about RNU, and that would equal dialysis for a patient with a solitary kidney. Obviously, nephron-sparing [treatment] is the most important thing [to] avoid an RNU and avoid dialysis. Secondly, for patients with a solitary kidney, you want to try to avoid as much manipulation and [potential] damage in procedures as possible, especially for someone with a single kidney. You also decrease that by using a mitomycin gel. [The] combination of nephron-sparing [treatment and fewer] interventions [will] hopefully keep these patients off dialysis, [and], yet, safely and effectively treat their cancer.

Transcript has been edited for clarity.