Is Non-Surgical Treatment of Bladder Cancer Durable? 24-Month Duration of Response Data From the ENVISION Phase 3 Trial Published in the Journal of Urology

KEY FINDINGS

• Trial: ENVISION (NCT05243550) - a multinational, prospective, single-arm phase 3 trial; 56 centres in the United States and Europe, 240 patients.
• Treatment: Intravesical UGN-102 (RTGel® reverse thermal hydrogel containing 75 mg mitomycin) once weekly for 6 weeks. 95% of patients (228/240) received all six doses.
• Complete response at month 3 (primary endpoint): 79.6% (191/240; 95% CI 73.9-84.5).
• Durability of response: Among those achieving a complete response, the probability of remaining event-free was 82.4% at month 12 and 72.2% at month 24 (Kaplan-Meier estimate).
• Regulatory: UGN-102 (ZUSDURI™) became the first and only drug approved by the FDA in the indication of recurrent LG-IR-NMIBC on 12 June 2025.

Background: An Unresolved Clinical Need

Low-grade, intermediate-risk non-muscle-invasive bladder cancer (LG-IR-NMIBC) is one of the most frequently encountered but least discussed problems in uro-oncological practice. The disease is rarely life-threatening; however, it has an extremely high tendency to recur. The standard approach of transurethral resection of bladder tumour (TURBT) - with or without a single postoperative dose of intravesical chemotherapy - does not adequately control recurrence.

The clinical consequence is this: these mostly elderly patients undergo repeated resections under general anaesthesia over a disease course exceeding ten years. Each intervention means anaesthetic risk, urethral trauma, loss of bladder capacity and an often overlooked psychological burden.

UGN-102 represents a different strategy aimed at breaking this cycle: primary chemoablation. Instead of resection, the goal is to dissolve the tumour with a drug. The distinguishing feature of the agent is its delivery system - RTGel® reverse thermal hydrogel is instilled into the bladder in liquid form at room temperature, gels at body temperature to provide sustained contact with the urothelial surface, and is gradually excreted in the urine.

Study Design

ENVISION is a multinational, prospective, single-arm pivotal phase 3 trial conducted in patients with a history of low-grade non-muscle-invasive bladder cancer requiring TURBT. Patients received a total of 6 intravesical UGN-102 instillations, once weekly. Response was assessed approximately 3 months after the first instillation by cystoscopy, urine cytology and, where necessary, biopsy.

The duration of response (DoR) reported in this analysis was defined as the time from complete response at month 3 to disease recurrence, progression or death from any cause. Event-free probabilities at 12 and 24 months were calculated by the Kaplan-Meier method using Brookmeyer-Crowley confidence intervals; median DoR was estimated with a Weibull model.

Key Results

Patients not achieving a response: No clinical response was achieved at month 3 in 20.4% of patients (n=49).

Durability Profile

The most notable finding of the trial is that the event rate remained stable over time. In patients achieving a complete response at month 3, event accumulation showed no unexpected acceleration over 24 months; the event-free probability moved from 82.4% at month 12 to 72.2% at month 24, that is, a predictable decline of approximately 10 points. The fact that median duration of response was not reached at a median follow-up of 23.7 months shows that the response was preserved in the great majority.

Safety

The most frequently reported treatment-related adverse events were dysuria, haematuria, urinary tract infection, urinary frequency and fatigue. The serious adverse event rate was reported as 12%; these included urinary retention (0.8%) and urethral stricture (0.4%). This profile should be assessed alongside the cumulative risk of the standard approach requiring repeated general anaesthesia and resection.

Methodological note: The duration-of-response population reported in this analysis (n=191 achieving complete response at month 3) differs from the efficacy population in the FDA prescribing information (USPI) (n=173). This distinction should be borne in mind when interpreting the data.

Implications for Clinical Practice

1. A new step in the treatment algorithm

LG-IR-NMIBC has been treated for decades as a purely surgical problem. The 79.6% complete response achieved with UGN-102 and durability maintained over two years show that chemoablation can be positioned in selected patients as an alternative - not complementary, but alternative - first-line approach to resection.

2. Particular value in patients at high anaesthetic risk

Recalling that 68% of the cohort was over 65, the value of a treatment option that can be delivered by catheter in an office setting is clear in the patient group in whom repeated general anaesthesia should be avoided because of cardiopulmonary comorbidity.

3. Preservation of bladder function and quality of life

The long-term cost of repeated resections is not only oncological: urethral stricture, reduced bladder capacity and storage symptoms accumulate cumulatively. Reducing the number of surgical interventions directly affects the patient's day-to-day functioning.

4. Easing the patient's psychological burden

In this patient group the physician's task is not only to control the tumour but to move the patient out of the position of "someone perpetually awaiting surgery". The two-year durability data provide a concrete and honest framework for discussion with the patient: when a complete response is achieved, approximately three quarters of patients are still disease-free at the end of two years.

5. Early identification of the non-responder

The failure to achieve a response at month 3 in approximately one fifth of patients underlines that protocol-based cystoscopic assessment must not be postponed. Chemoablation is not a surveillance strategy; response assessment must be performed on time and, when residual disease is detected, surgical management must follow without delay.

Limitations

ENVISION is a single-arm trial. The absence of a concurrent control group prevents direct comparison of the results with the standard TURBT approach; no claim of relative superiority can therefore be made. Indeed, the FDA's Oncologic Drugs Advisory Committee (ODAC) voted 4 to 5 at its May 2025 meeting that the benefit-risk profile was not favourable; the agent was nevertheless approved in June 2025. In addition, the fact that 98% of the cohort was white limits the generalisability of the findings to other populations. The trial continues under a post-marketing commitment with the FDA to evaluate long-term safety and efficacy.

Conclusion

The 24-month duration-of-response data from the ENVISION trial show that intravesical chemoablation in recurrent low-grade intermediate-risk non-muscle-invasive bladder cancer is not merely a short-term clearance of tumour; the response achieved is largely maintained over two years. With the interpretative limitation of the single-arm design duly noted, these findings provide an evidence-based basis for breaking out of the cycle of repeated resection in selected patients.

In uro-oncology, genuine progress often arises not from a new surgical technique but from making the avoidance of surgery safe. These data are a concrete example of progress in that direction.

References

• Prasad SM, et al. UGN-102 for Recurrent Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer: 24-Month Duration of Response Results From the Phase 3 ENVISION Trial. Journal of Urology. 2026. - auajournals.org
• UroToday. AUA 2026: Treatment with UGN-102 in Patients with Recurrent Low-Grade Intermediate Risk Non-Muscle Invasive Bladder Cancer: 24-Month Duration of Response Data from the Phase 3 ENVISION Trial. - urotoday.com
• Urology Times. FDA approves mitomycin intravesical solution for recurrent LG-IR-NMIBC. - urologytimes.com
• Renal & Urology News. UGN-102 Has Durable Response Over 24 Months for Low-Grade, Intermediate-Risk NMIBC. - renalandurologynews.com
• Prasad SM, Shishkov D, Vladimirov Mihaylov N, et al. Primary Chemoablation of Recurrent Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer with UGN-102: A Single-Arm, Open-Label, Phase 3 Trial (ENVISION). J Urol. 2025;213(2):205-216.
• ClinicalTrials.gov. A Phase 3 Single-Arm Study of UGN-102 for Treatment of Low Grade Intermediate Risk Non-Muscle-Invasive Bladder Cancer (ENVISION), NCT05243550. - clinicaltrials.gov