The incorporation of mitomycin intravesical solution (Zusduri; UGN-102) into the recurrent, low-grade, intermediate-risk non–muscle-invasive bladder cancer (NMIBC) treatment arena marks a paradigm shift toward the nonsurgical management of this disease, according to William C. Huang, MD.
On June 12, 2025, the FDA approved UGN-102 for the treatment of adult patients with recurrent, low-grade, intermediate-risk NMIBC.1 This regulatory decision was backed by data from the phase 3 ENVISION trial (NCT05243550), in which, at 3 months after the first instillation of UGN-102, the complete response (CR) rate among evaluable patients (n = 223) was 78% (95% CI, 72%-83%). Additionally, the rate of patients still in response at 12 months was 79% (range for DOR, 0 to 25+ months).
Updated data from ENVISION demonstrated that among evaluable patients (n = 240), the 3-month CR rate was 79.6% (95% CI, 73.9%-84.5%), and the estimated duration of response (DOR) rate at 18 months after CR was 80.6% (95% CI, 74.0%-85.7%).2 In total, 57% of patients had experienced any-grade treatment-emergent adverse effects (AEs), the most common being dysuria (23%), hematuria (8.3%), urinary tract infection (7.1%), pollakiuria (6.7%), fatigue (5.4%), and urinary retention (5.0%). In total, 2 serious AEs were considered treatment related.
“A lot of us are excited that we now have a new tool in our armamentarium for the management of bladder cancer,” Huang said in an interview with OncLive®. “Bladder cancer is a lifelong disease, and for many patients, [UGN-102] is an exciting new way of offering them a treatment that can prevent the need to go to the operating room or the need to have a surgical procedure. [This is a treatment] that has demonstrable, durable benefit after the initial [administration]. This will make a lot of patients happy.”
In the interview, Huang discussed the significance of this approval, key efficacy and safety data from ENVISION, and patient subgroups that may derive the most benefit from the availability of this therapy.
Huang is a professor in the Departments of Urology and Radiology at NYU Grossman School of Medicine; as well as vice chair of Clinical Affairs in the Department of Urology, chief of the Urology Service, and codirector of the Robotic Surgery Center at Tisch Hospital in New York, New York.
OncLive: What are the clinical implications of the FDA approval of UGN-102 for patients with low-grade, intermediate-risk NMIBC?
Huang: For the first time, we have a noninvasive, completely novel way of treating patients with low-grade, intermediate-risk bladder cancer. This is a paradigm shift for many patients. [The management of this disease has gone from] something that’s primarily been surgical to something that is nonsurgical and chemoablative, which is a completely different path than we’ve been on for decades.
What patient population did ENVISION enroll?
The trial enrolled patients with recurrent, low-grade, intermediate-risk bladder cancer. These are patients who had multiple low-grade tumors or were solitary tumor [smaller than] 3 cm in size and/or who had recurrences within 12 months of their original treatment. This cohort represents a lot of patients we see [in the clinic]: patients who have a significant risk of having more tumors throughout their lifetime but who may not have a significant risk of disease progression or dying of their bladder cancer without appropriate treatment.
What was the design of ENVISION?
This was a single-arm, open-label, phase 3 trial, so there was no control arm. These patients had to have biopsy-proven, low-grade, recurrent bladder cancer and fit the criteria of having intermediate-risk disease with multifocality and recurrences. These patients had to have undergone a cold cup biopsy, but the tumor had to be left in place. In other words, there was a bladder tumor that was left untreated to [evaluate] the efficacy of primary chemoablation of the bladder cancer. Once we identified the appropriate patients, UGN-102 was administered once a week for a total of 6 weeks. Three months after initiation of the treatment, the patients underwent a cystoscopy and assessment of what we consider a CR, which is negative urine cytology and no visual disease seen in the bladder.
What were the key efficacy and safety outcomes from this trial?
[At 18 months of follow-up], the ENVISION trial data demonstrated a CR rate at 3 months of 79.6%, which meant that at 3 months, approximately 80% of the patients had a CR after primary chemoablation of the tumor they had in their bladder. Secondary end points included DOR for those who had completely responded, along with treatment-emergent AEs. The AEs were all relatively minor. There were no grade 4 or 5 AEs that were related to the drug itself. [Thirty-three] patients had grade 3 AEs, but the AE rates were extremely low.
What advice would you put forth to colleagues about integrating UGN-102 into clinical practice?
Many urologists have patients who tend to recur on a regular basis. [UGN-102] will be a nice way of treating these patients without necessarily having to put them through multiple procedures per year trying to manage or control their disease. For another subset of patients—those who are ill, those who are receiving blood thinners, and those who may not tolerate going to the operating room on an infrequent basis—[UGN-102] will be another [treatment option that does not require exposing] them to the risks of general anesthesia and putting them through an operation. There are multiple subsets of patients that this is a great alternative for.
References
- FDA approves mitomycin intravesical solution for recurrent low-grade intermediate-risk non-muscle invasive bladder cancer. FDA. June 12, 2025. Accessed August 22, 2025. http://bit.ly/4fP2QDp
- Prasad SM, Mihaylov NV, Khuskivadze A, et al. Duration of response (DoR) following treatment with UGN-102 in patients with recurrent, low-grade, intermediate-risk, non-muscle invasive, bladder cancer: 18-month DoR data from the phase 3 ENVISION trial. J Clin Oncol. 2025;43(suppl 16):4598. doi:10.1200/JCO.2025.43.16_suppl.4598