• Nir Kleinmann, Surena F Matin, Phillip M Pierorazio, John L Gore, Ahmad Shabsigh, Brian Hu, Karim Chamie, Guilherme Godoy, Scott Hubosky, Marcelino Rivera, Michael O'Donnell, Marcus Quek, Jay D Raman, John J Knoedler, Douglas Scherr, Joshua Stern, Christopher Weight, Alon Weizer, Michael Woods, Hristos Kaimakliotis, Angela B Smith, Jennifer Linehan, Jonathan Coleman, Mitchell R Humphreys, Raymond Pak, David Lifshitz, Michael Verni, Mehrad Adibi, Mahul B Amin, Elyse Seltzer, Ifat Klein, Marina Konorty, Dalit Strauss-Ayali, Gil Hakim, Mark Schoenberg, and Seth P Lerner.
• Department of Urology, Sheba Medical Center, Ramat Gan, Israel.
• Lancet Oncol. 2020 Jun 1; 21 (6): 776-785.

BackgroundMost patients with low-grade upper tract urothelial cancer are treated by radical nephroureterectomy. We aimed to assess the safety and activity of a non-surgical treatment using instillation of UGN-101, a mitomycin-containing reverse thermal gel.MethodsIn this open-label, single-arm, phase 3 trial, participants were recruited from 24 academic sites in the USA and Israel. Patients (aged ≥18 years) with primary or recurrent biopsy-proven, low-grade upper tract urothelial cancer (measuring 5-15 mm in maximum diameter) and an Eastern Cooperative Oncology Group performance status score of less than 3 (Karnofsky Performance Status score >40) were registered to receive six instillations of once-weekly UGN-101 (mitomycin 4 mg per mL; dosed according to volume of patient's renal pelvis and calyces, maximum 60 mg per instillation) via retrograde catheter to the renal pelvis and calyces. All patients had a planned primary disease evaluation 4-6 weeks after the completion of initial therapy, in which the primary outcome of complete response was assessed, defined as negative 3-month ureteroscopic evaluation, negative cytology, and negative for-cause biopsy. Activity (complete response, expected to occur in >15% of patients) and safety were assessed by the investigator in all patients who received at least one dose of UGN-101. Data presented are from the data cutoff on May 22, 2019. This study is registered with ClinicalTrials.gov, NCT02793128.FindingsBetween April 6, 2017, and Nov 26, 2018, 71 (96%) of 74 enrolled patients received at least one dose of UGN-101. 42 (59%, 95% CI 47-71; p<0·0001) patients had a complete response at the primary disease evaluation visit. The median follow-up for patients with a complete response was 11·0 months (IQR 5·1-12·4). The most frequently reported all-cause adverse events were ureteric stenosis in 31 (44%) of 71 patients, urinary tract infection in 23 (32%), haematuria in 22 (31%), flank pain in 21 (30%), and nausea in 17 (24%). 19 (27%) of 71 patients had study drug-related or procedure-related serious adverse events. No deaths were regarded as related to treatment.InterpretationPrimary chemoablation of low-grade upper tract urothelial cancer with intracavitary UGN-101 results in clinically significant disease eradication and might offer a kidney-sparing treatment alternative for these patients.FundingUroGen Pharma.Copyright © 2020 Elsevier Ltd. All rights reserved.

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