Effect of Administration Route of UGN-101 in Upper Tract Urothelial Carcinoma

UGN-101, or Jelmyto, is a mitomycin-based hydrogel approved for low-grade upper tract urothelial carcinoma chemoablation. Clinical trials demonstrated that 59% of patients on UGN-101 treatment had a complete response, of whom more than 80% experienced long-term response. UGN-101 can be administered via an anterograde or retrograde route, but there is a lack of studies comparing the outcomes across the two administration routes. Linehan et al. compared response and recurrence among patients treated with anterograde versus retrograde UGN-101 administration.

The study cohort consisted of 132 patients treated with at least one dose of UGN-101, among whom 43% received anterograde administration, and 57% received retrograde administration. The mean age was 73.8 years. More patients in the retrograde group (65%) had visible disease at UGN-101 induction than in the anterograde group (45%, p = 0.02). Seven patients underwent radical nephroureterectomy (RNU) after treatment. There was no significant difference in response between the anterograde and retrograde groups (p = 0.1). However, there was a trend toward a higher complete response rate in the anterograde group (60%) than in the retrograde group (48%). At a median follow-up of approximately eight months, there was no difference in recurrence rates between groups.

The overall ureteral stricture rate throughout the study was 23%. At induction, patients in the retrograde group exhibited a significantly higher rate of ureteral stricture (27%) than those in the anterograde group (3%, p = 0.005). In both groups, approximately 12% of patients experienced a grade of 3 or higher complication. In the retrograde group, these events included acute kidney injury, urosepsis, failure to thrive, cerebrovascular accident, pancytopenia, and pruritis. In the anterograde administration group, the events included anemia, severe cystitis, rash, urosepsis, and herpes zoster. Among the 47 patients with a ureteral tumor, 28% were treated with the anterograde route, and 72% were treated with the retrograde route. Two patients in the anterograde group subsequently underwent RNU (compared to zero in the retrograde group, p = 0.116).

An important finding is the significantly lower rate of strictures with antegrade administration of UGN-101 without compromising oncological efficacy. Prospective confirmation of these findings can improve the adoption of this important therapeutic modality for patients with low-grade upper tract urothelial carcinoma.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine

References:

Linehan J, Gottlieb J, Woldu SL, et al. Route of Administration for UGN-101 and Impact on Oncological and Safety Outcomes [published online ahead of print, 2023 May 30]. Eur Urol Focus. 2023;S2405-4569(23)00123-2. doi:10.1016/j.euf.2023.05.012

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