No abstract

Lynch syndrome is a common genetic disease that is an underappreciated cause of upper tract urothelial carcinoma and possibly other urological cancers. Optimal screening for upper tract urothelial carcinoma in this population is unclear. Further study is needed to identify the best screening test and interval of testing. Urologists should consider routine tissue testing of de novo upper tract urothelial carcinoma tissue in individuals at risk.

Word count: 250/250Purpose: To evaluate long-term safety and durability of response to UGN-101, a mitomycincontaining reverse thermal gel, as primary chemoablative treatment for low-grade upper tract urothelial carcinoma (UTUC). Materials and Methods:In this open-label, single-arm, multi-center, phase 3 trial (NCT02793128), patients ≥18 years of age with primary or recurrent biopsy-proven low-grade UTUC received 6 once-weekly instillations of UGN-101 via retrograde catheter to the renal pelvis and calyces. Those with complete response (defined as negative ureteroscopic evaluation, negative cytology, and negative for-cause biopsy) 4-6 weeks after the last instillation were eligible for up to 11 monthly maintenance instillations and were followed for ≥12 months with quarterly evaluation of response durability. Durability of complete response was determined by ureteroscopic evaluation; duration of response was estimated by the Kaplan-Meier method.Treatment-emergent adverse events (TEAEs) were monitored. Results:Of 71 patients who initiated treatment, 41 (58%) had complete response to induction therapy and consented to long-term follow up; 23/41 patients (56%) remained in complete response after 12 months (95% CI: 40, 72), comprising 6/12 (50%) who did not receive any maintenance instillations and 17/29 (59%) who received ≥1 maintenance instillation. Kaplan-Meier analysis of durability was estimated as 82% (95% CI: 66, 91) at 12 months. Ureteric stenosis was the most frequently reported TEAE (31/71, 44%); an increasing number of instillations appeared to be associated with increased incidence of urinary TEAEs.