To evaluate the efficacy and safety of UGN-102 chemoablation for the primary treatment of patients with recurrent low-grade intermediate-risk nonmuscle-invasive bladder cancer.
Materials and Methods
ENVISION is an ongoing, multinational, single-arm, Phase 3 study in patients with a biopsy-proven recurrence of untreated low-grade intermediate-risk nonmuscle-invasive bladder cancer. Patients received 6 weekly intravesical instillations of UGN-102 (mitomycin; outpatient setting) and were evaluated at 3 months. Patients achieving complete response (CR; negative cystoscopic examination, cytology, and for-cause biopsy) were surveilled regularly until recurrence, progression, or death. Patients who remain disease-free will be followed up to 5 years, and further results will be reported in the future.
Results
Of 240 patients enrolled, 228 (95%) received all 6 planned doses; 191 (79.6%; 95% CI, 73.9-84.5) achieved CR at 3 months, with an 82.3% (95% CI, 75.9-87.1) probability of response 12 months later. Median duration of response was not estimable over a median 13.9-month follow-up period. The most common adverse events (≥5.0% of patients) were dysuria, hematuria, urinary tract infection, pollakiuria, fatigue, and urinary retention; generally mild/moderate and resolved/resolving. Serious adverse events were observed in 29/240 (12.1%), 2 were treatment-related (urinary retention/urethral stenosis), both resolved.
Conclusions
Primary chemoablation with UGN-102 in patients with recurrent low-grade intermediate-risk nonmuscle-invasive bladder cancer resulted in a 79.6% CR rate. Patients achieving a CR had an 82.3% likelihood of remaining disease-free 1 year later. The benefit–risk profile was favorable, supporting UGN-102 as a nonsurgical alternative for transurethral resection of bladder tumors in this patient population. Limitations of this study included lack of tumor sizing after the diagnostic biopsy.
Trial Registration
ClinicalTrials.gov Identifier: NCT05243550
In recent years, we observed a growing body of evidence investigating stratification and prognosis outcomes from low- and intermediate non-muscle invasive bladder cancer. Specifically, a wide variety of non-surgical and conservative approaches have been described and tested ranging from chemoablation up to the introduction of active surveillance as new potential clinical alternatives in the management and care of specific risk categories.
Low-grade intermediate-risk non-muscle-invasive bladder cancer (LG-IR-NMIBC) is indeed a challenge in urology due to its recurrent nature and the limitations of current treatment modalities. In this commentary we will discuss the results of the recently published ENVISION trial by Prasad et al.
This is a Phase 3, open-label, single-arm study, which evaluated UGN-102, a chemoablative reverse thermal gel formulation of mitomycin, as a potential nonsurgical alternative to transurethral resection of bladder tumour (TURBT). The study aimed to address gaps in the management of LG-IR-NMIBC by assessing UGN-102's oncologic efficacy, perioperative safety, and durability in terms of recurrence rates.
The natural history of LG-IR-NMIBCs is indeed characterised by multifocality and high recurrence rate, traditionally managed through TURBT, with all the inherent limitations and quality issues related to endoscopic procedures pathways. Additionally, despite consolidated guideline recommendations for intravesical postoperative or adjuvant therapies, the idea is that many patients in real-world-practice will receive endoscopic resections and/or biopsy or fulguration alone, negatively affecting recurrence rates. In this study, the authors explore the experimental utilisation of UGN-102 as minimally invasive, intravesical alternative designed to provide sustained local exposure to mitomycin as to optimise outcomes.
The ENVISION trial enrolled 240 patients across 56 sites in 10 countries, targeting individuals with biopsy-confirmed LG-IR-NMIBC. Patients underwent six weekly instillations of UGN-102 in an outpatient setting, with primary evaluation at three months for complete response (CR), defined by negative cystoscopy, cytology, and for-cause biopsy results. Responders were followed for up to 12 months, with plans for extended five-year follow-up.
Most of the patient presented with multifocal tumours (82.8%) and a mean aggregate tumour size of 2.5cm. Inclusion criteria required at least one prior episode of LG-IR-NMIBC, while patients with muscle-invasive or high-grade disease within two years were excluded. Among 240 patients, 191 (79.6%; 95% CI: 73.9-84.5) achieved CR at three months. Probability of CR at 12 months was 82.3% (95% CI: 75.9-87.1). The median duration of response (DOR) was not estimable due to limited recurrences within the 13.9-month follow-up.
Regarding the safety profile, UGN-102 demonstrated favourable outcomes. Treatment-emergent adverse events (TEAEs) occurred in 57.1% of patients. The most common TEAEs included dysuria (22%), haematuria (8.3%), and urinary tract infection (7.1%). Serious adverse events were reported in 12.1% of patients, with only two cases (urinary retention and urethral stenosis) deemed treatment-related, both resolving without long-term complications.
The main limitations of the study highlighted by the authors rely on the study's single-arm design with no direct comparisons with TURBT or other therapies. Additionally, tumour size assessments relied on visual estimation, which may introduce variability.
As per conclusions, UGN-102 may represent an adjunct to currently available therapeutic alternatives for recurrent LG-IR-NMIBC, with high efficacy and an acceptable safety profile. As to rolling out UGN-102 as a minimally invasive alternative to endoscopy and resecting techniques, we will need to wait for the longer follow-up analysis scheduled in the future.. Surely, the ENVISION trial may provide further insights into long-term outcomes and the broader applicability of this innovative treatment approach in the LG-IR-NMIBC.