SES AUA 2022: Primary Chemoablation of Low-Grade Intermediate-Risk Non-Muscle-Invasive Bladder Cancer Using UGN-102, A Mitomycin-Containing Reverse Thermal Gel (OPTIMA II): A Phase 2B, Open-Label, Single-Arm Trial

( The 2022 Southeastern Section of the AUA’s annual meeting included a bladder cancer session and Dr. Angela Smith discussing results of OPTIMA II, a phase 2b, open-label, single arm trial assessing primary chemoablation of low-grade intermediate risk non-muscle invasive bladder cancer (NMIBC) using UGN-102. The standard of care for low-grade intermediate-risk NMIBC is transurethral resection of bladder tumors (TURBT) under general anesthesia. However, low-grade intermediate-risk NMIBC is a highly recurrent malignancy, and patients often endure repeated surgeries that may be associated with significant postoperative and long-term morbidity. OPTIMA II was designed to evaluate efficacy and safety of UGN-102, a mitomycin containing reverse thermal gel, as primary chemoablative therapy in patients with low-grade intermediate-risk NMIBC.

This prospective, phase 2b, open-label, single-arm trial recruited adult patients with biopsy-proven low-grade intermediate-risk NMIBC. Patients were treated with 6 once-weekly instillations of UGN-102 in an office setting. The trial design of OPTIMA II is as follows: 


The primary endpoint was complete response, defined as negative endoscopic examination, negative cytology, and negative for-cause biopsy, 3 months after treatment initiation. Patients who achieved complete response were followed quarterly for up to 12 months to assess durability of response. Duration of response was estimated by the Kaplan-Meier method and safety was monitored throughout the study.

There were 63 patients enrolled in the study and treated with UGN-102 (intent-to-treat population). The mean age was 70.5 years (range 33-96), 60.3% of patients were male, and 87% of patients were white. Overall, 78% of patients had recurrent low-grade NMIBC, and 44% had a previous episode within 1 year of the current diagnosis. Recurrent patients had a mean of 4.4 (range: 1-12) prior NMIBC episodes and underwent a mean of 4 (maximum: 13) prior TURBTs.  There were 41 of 63 (65%) patients that achieved complete response at 3 months, of whom 39 (95%), 30 (73%), and 25 (61%) remained disease-free at 6, 9, and 12 months after treatment initiation, respectively. There were 13 of 41 (32%) patients with complete response at 3 months that had disease recurrence. The Kaplan-Meier estimate of duration of complete response (3-month complete response analysis set) is as follows:


Any treatment-emergent adverse event occurred in 90% of patients, any treatment drug- or procedure-related adverse event occurred in 63% of patients, and any treatment-emergent adverse event leading to discontinuation occurred in 10% of patients. Common adverse events (≥10% of patients) were primarily mild or moderate and included dysuria (41%), pollakiuria (21%), hematuria (16%), micturition urgency (14%), urinary tract infection (14%), and fatigue (11%). One death occurred but was not related to treatment.

Dr. Smith concluded her presentation of the OPTIMA II phase 2b trial with the following take-home messages:

  • Primary chemoablation of low-grade intermediate-risk NMIBC using UGN-102 results in a high rate of disease eradication (65% complete response rate at 3 months) with encouraging durability
  • Most commonly reported treatment-emergent adverse events were dysuria, urinary frequency, hematuria, micturition urgency, urinary tract infection, and fatigue
  • UGN 102 may provide an alternative to repetitive TURBT for patients with low-grade intermediate-risk NMIBC
  • A phase 3, randomized, controlled trial of UGN-102 for treatment of low-grade intermediate-risk NMIBC is ongoing (NCT03558503)
Presented by: Angela B. Smith, MD, MS, University of North Carolina School of Medicine, Chapel Hill, NC

Co-Authors: K. Kent Chevli, Neal D. Shore, Andrew Trainer, Daniel Saltzstein, Yaron Ehrlich, Jay D. Raman, Boris Friedman, Richard D’Anna, David Morris, Brian Hu, Mark Tyson, Alexander Sankin, Max Kates, Jennifer Linehan, Douglas Scherr, Steven Kester, Michael Verni, Karim Chamie, Lawrence Karsh, Arnold Cinman, Andrew Meads, Soumi Lahiri, Madlen Malinowski, Nimrod Gabai, Sunil Raju, Mark Schoenberg, Elyse Seltzer, William C. Huang

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