SES AUA 2022: Preliminary Results Of A Single Arm Phase II Trial Of Intraoperative Intravesical Mitomycin C During Nephroureterectomy For Urothelial Carcinoma

( The 2022 Southeastern Section of the AUA’s annual meeting included a bladder cancer session and Dr. Hiroko Miyagi discussing preliminary results of a single arm phase II trial of intraoperative intravesical mitomycin C during nephroureterectomy for urothelial carcinoma. Intravesical recurrence occurs in ~40% of patients during follow-up, however a single post-operative instillation of intravesical chemotherapy reduces the risk of bladder tumor recurrence within the first year following radical nephroureterectomy.  However, there is a paucity of evidence regarding the timing of administration of intravesical chemotherapy. A retrospective review of 51 patients who underwent radical nephroureterectomy had a bladder tumor recurrence rate of 16% (intra-operative mitomycin C) versus 33% (post-operative instillation of mitomycin C).1 As such, the objective of this study was to evaluate the impact of intraoperative instillation of mitomycin C during nephroureterectomy on bladder tumor recurrence.

A prospective single arm trial of intraoperative intravesical mitomycin (40 mg/40 mL) during nephroureterectomy and bladder repair, was completed at a single center between November 2018 and January 2021. The primary endpoint was bladder tumor recurrence at 12 months following nephroureterectomy. The planned sample size was 55 patients with a planned interim analysis after the first 17 patients reached evaluation of the primary endpoint. Key eligibility criteria included biopsy proven diagnosis of upper tract urothelial carcinoma prior to nephroureterectomy and no evidence of bladder cancer during the prior year in patients with a history of bladder cancer. Surveillance for bladder tumor recurrence included office cystoscopy and urine cytology at 3, 6, 9, and 12 months postoperatively. The trial flow chart/protocol is as follows:

There were 29 patients enrolled during the study period, with 22 patients having data available to assess the primary endpoint. Of these 22 patients, 72% (16/22) were male, 14% (3/22) had a history of stage I bladder cancer, and 91% (20/22) underwent a minimally invasive nephroureterectomy. Pathology at nephroureterectomy included 82% (19/22) with high grade disease, 68% (15/22) with Tis-T1 disease, and 27% (6/22) with concomitant carcinoma in situ in the nephroureterectomy specimen. No grade 3 or greater adverse events were attributed to intraoperative instillation of mitomycin C were noted. The 12-month bladder tumor recurrence rate was 45% (10/22) (100% HG, 0%Tis, 90%Ta, 10% T1). The trial was closed during the planned interim analysis due to the high rate of bladder tumor recurrence compared to historical controls. As follows is the Kaplan-Meier survival curve for time-to-recurrence of bladder tumors within the first year of intra-operative instillation of mitomycin C:


Dr. Miyagi concluded her presentation assessing the impact of intraoperative instillation of mitomycin C during nephroureterectomy on bladder tumor recurrence with the following take-home messages:

  • Intraoperative instillation of mitomycin C did not decrease bladder tumor recurrence compared to historical data evaluating post-operative instillation
  • Results from other ongoing trials evaluating the efficacy of intraoperative chemotherapy during nephroureterectomy are awaited

Presented By: Hiroko Miyagi, MD, Department of Urology, University of Florida, Gainesville, FL

Co-Authors: Nikhil Batra, Shu Wang, Wayne Brisbane, Li-Ming Su, Padraic O'Malley, Paul Crispen

Affiliations: Department of Urology, University of Florida, Gainesville, FL

Written By: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 86th Annual Meeting of the Southeastern Section of the American Urological Association, San Juan, PR, Mar 16 – 19, 2022

1. Noennig B, Bozorgmehri S, Terry R, Otto B, Su LM, Crispen PL. Evaluation of Intraoperative Versus Postoperative Adjuvant Mitomycin C with Nephroureterectomy for Urothelial Carcinoma of the Upper Urinary Tract. Bladder Cancer. 2018;4(4):389-394