Kidney-sparing therapy for low-grade upper tract urothelial cancer

Nov. 30, 2022

Nota: este contenido se creó antes de la pandemia de la enfermedad por coronavirus 2019 (COVID-19) y no describe los protocolos adecuados para la pandemia. Respeta todas las pautas recomendadas por los Centros para el Control y la Prevención de Enfermedades relativas al uso de mascarillas y al distanciamiento físico.

Upper tract urothelial cancer (UTUC) is a rare condition that makes up only 5% of all urologic neoplasms. It's most often diagnosed in patients older than 70 years. Most patients with low-grade UTUC are treated with radical nephroureterectomy. Mayo Clinic, along with 23 other academic sites in the U.S. and Israel, was part of a study using a mitomycin-containing reverse thermal-sensitive gel as a kidney-sparing treatment option for low-grade UTUC.

"The unique thing about the gel is that it offers an opportunity to preserve the kidney," says Mitchell R. Humphreys, M.D., a urologist at Mayo Clinic in Phoenix/Scottsdale, Arizona. "The mitomycin in the gel actually chemoablates or destroys the cancerous cells."

In the past, the problem with such therapies has been the dwell time inside the body. As a reverse thermal-sensitive gel, though, the mitomycin is in a liquid state at colder temperatures. As it warms up to body temperature, it takes on a gelatin state that is slower to dissolve but still does not obstruct kidney function.

Phase 3 trial and durability of response

The mitomycin-containing gel was initially studied in an open-label, single-arm phase 3 trial called OLYMPUS from April 6, 2017, to November 26, 2018. Results of this study were published in the June 2020 issue of The Lancet Oncology.

Of the 74 patients enrolled in the trial, 61 received the full protocol of six instillations of once-weekly gel via retrograde catheter to the renal pelvis and calyces. Complete response was defined as a negative three-month ureteroscopic evaluation, negative cytology and negative for-cause biopsy. Forty-two patients (59%) showed complete response at their primary disease evaluations 4 to 6 weeks after the initial therapy.

Durability of response for this trial was reported in the April 2022 edition of The Journal of Urology. The 41 patients who had complete response were eligible for up to 11 monthly maintenance instillations. This cohort was followed for more than 12 months. Durability was determined by ureteroscopic evaluation and estimated with the Kaplan-Meier method.

Of the 41 patients in the cohort, 29 received maintenance therapy, 17 of whom remained in complete remission after 12 months. An additional six patients who did not receive maintenance therapy also remained in complete remission, for a total of 23 patients showing complete response after 12 months. The Kaplan-Meier analysis of durability was estimated as 82%.

"This gives patients hope for renal preservation," said Dr. Humphreys. "It's something more than we've been able to do before."

The most common treatment-emergent adverse events were ureteric stenosis or stricture in 31 patients (44%), urinary tract infection in 23 patients (32%), hematuria in 22 patients (31%), flank pain in 21 patients (30%), and nausea in 17 patients (24%). Nineteen of these patients had serious adverse events.

New method of antegrade administration

While mitomycin has been approved by the FDA for treatment of low-grade UTUC, the stricture rate of the protocol as initially outlined is relatively high. Dr. Humphreys and his colleagues recognized this throughout the course of the study and began using antegrade rather than retrograde administration of the gel.

"One of the things we did very early on was to administer the gel from the top down, or antegrade," said Dr. Humphreys. "The advantage is that it can be done in the clinic without anesthesia and it doesn't require manipulation of the ureter or kidney."

With the antegrade procedure, the mitomycin gel was administered through a percutaneous nephrostomy tube. Four centers took part in the antegrade procedure for 32 patients. A pooled analysis of their findings reported that only three patients (9%) developed ureteric stenosis, making it a much safer administration option for this medication. Results were published in BJU International in October 2022.

"It's life-changing for patients who thought they were going to be losing a kidney," said Dr. Humphreys. "The patients we're treating with this therapy are very happy."

For patients at Mayo Clinic, the mitomycin-containing gel is compounded onsite for a more direct and individualized treatment experience with more flexibility in scheduling. This therapy is currently available only for patients with low-grade UTUC. Further research is needed for high-grade diagnoses.

For more information

Kleinmann N, et al. Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): An open-label, single-arm, phase 3 trial. The Lancet Oncology. 2020;21:76.

Matin SF, et al. Durability of response to primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel: OLYMPUS trial final report. The Journal of Urology. 2022;207:779.

Rose KM, et al. Antegrade administration of mitomycin gel for UTUC via percutaneous nephrostomy tube: A multi-institutional retrospective cohort study. BJU International. 2022. In press.

Refer a patient to Mayo Clinic.