Impact of tumor burden or focality in recurrent low-grade intermediate-risk non-muscle-invasive bladder cancer on response to treatment with UGN-102: A substudy of the phase 3 ENVISION trial.
Authors: Sandip M Prasad, Dimitar Shishkov, Nikola V Mihaylov, Alexandre Khuskivadze, Pencho Genov, Vasyl Terzi, Max Kates, William C. Huang, Michael J Louie, Sunil Raju, Brent Burger, Andrew Meads, Mark Schoenberg
Journal: Journal of Clinical Oncology (2025)

776 Background: The ENVISION phase 3 study (NCT05243550) treated patients withlow-grade intermediate-risk non-muscle-invasive bladder cancer (LG-IR-NMIBC) with UGN-102, a reverse thermal hydrogel containing mitomycin. Primary efficacy and safety results were previously reported. Complete response (CR) rate at 3 months was 79.6%, with an 82.3% probability of remaining in response 12 months later by Kaplan-Meier estimate. We conducted a post-hoc analysis to evaluate if certain tumor characteristics influenced response rate and durability. Methods: In the single-arm ENVISION study, 240 patients with LG-IR-NMIBC received 6 weekly intravesical instillations of UGN-102; 3 months after the first dose, patients were examined for the presence of bladder cancer using cystoscopy, urine cytology testing, and for-cause biopsy. Patients achieving CR (no detectable disease) entered the follow-up period and were surveilled regularly for recurrence. Between group comparisons were performed for CR rate (CRR) at 3 months and duration of response (DOR) 12 months after achieving CR in patients with tumor burden ≤ or &gt;3 cm (calculated as total length of all tumors), and for single vs multiple tumors. Hazard ratios (HRs) of DOR were calculated using a Cox Proportional Hazards (PH) model, and p-values calculated using a log-rank test; p-values for the comparison of CRR were calculated using Fisher’s Exact Test. Results: CRR at 3 months was 82.8% vs 73.2% for patients with tumor burden ≤3 cm and &gt;3 cm, respectively. Of the patients with CR at 3 months, 15.4% vs 20% experienced recurrence of LG disease, progression (either in stage or grade), or death by 15 months. In patients with multiple vs single tumors, 3-month CR was 79.3% vs 82.9%, with recurrence rates of 18.5% vs 11.8%. DOR HRs were not statistically significant for any comparison made (table). Conclusions: Although a non-significant higher event rate was observed at 3 months for patients with a higher tumor burden, the CRR was robust, and the majority of patients remained event free at 15 months. These results demonstrate that chemoablation using UGN-102 results in a high, clinically meaningful CRR in patients with recurrent LG-IR-NMIBC, regardless of tumor burden or multifocality. Study limitations were the small sample size of the comparator groups, single arm design, and post-hoc nature of the analysis. UGN-102 may represent a valuable treatment option for many patients with LG-IR-NMIBC. Clinical trial information: NCT05243550 . CR at 3 months CRR(95% CI) / p value* Recurrence within 15 months DOR HR(95% CI) / p value* Tumor size ≤3 cm&gt;3cm 149/180 (82.8%)30/41 (73.2%) 1.13 (0.93–1.38) / p=0.1854 23/149 (15.4%)6/30 (20.0%) 0.777 (0.317–1.909) / p=0.5816 Tumor count MultipleSingle 157 /198 (79.3%)34/41 (82.9%) 0.96 (0.82 –1.12) / p=0.6740 29/157 (18.5%)4/34 (11.8%) 1.644 (0.578–4.677) / p=0.3459 *Nominal.