Introduction

Endoscopic resection of low-grade (LG) tumors in patients with non-muscle invasive bladder cancer (NMIBC) is limited by incomplete imaging of all lesions, deep resections that preclude use of immediate intravesical therapy, and significant pain that hastens drainage of any intravesical agent. VesiGel, a novel sustained release thermosensitive hydrogel formulation of Mitomycin C (MMC), was developed to overcome these limitations. This study evaluated the primary chemoablative properties of VesiGel in the treatment of patients with LG NMIBC as an alternative to transurethral resection of bladder tumor (TURBT).

Methods

64 patients with LG NMIBC who were all eligible for TURBT were enrolled in the study after informed consent was obtained. The study consisted of 3 groups: Group A- VesiGel 0.06% (40mg at 64mL gel; n=20); Group B- VesiGel 0.12% (80mg at 64mL gel; n=22), and Group C- MMC 0.1% (40mg in 40mL water; n=23). All patients underwent 6 weekly instillations. Response was evaluated 2-4 weeks after the last instillation via cystoscopy and biopsy. Patients who demonstrated a CR were followed without any additional treatment. Recurrence and follow up were calculated based on the first cystoscopy documenting a CR. Kaplan Meier survival analysis was used to compare recurrence free survival (RFS).

Results

CR rate was 45.0%, 86.4% and 69.6% in groups A, B and C, respectively. For patients with smaller tumors (size ≤1cm²), the CR rate was 50.0%, 87.5% and 77.8%, respectively. For larger tumors (>1cm²), the CR was 40%, 83.3% and 40.0%, respectively. For patients with ≤3 tumors, the CR rate was 50.0%, 81.3% and 80.0%, while for patients with >3 tumors, the CR rate was 0%, 100% and 50%, respectively. Of the 44 patients with a CR, 36 had follow up data available. Kaplan-Meier survival analysis showed no difference in RFS between groups (log rank test: p=0.46).

Conclusions

These preliminary results provide an initial indication of the ablative effect of VesiGel and its potential use as an alternative to TURBT. Compared with aqueous MMC 0.1%, VesiGel 0.12% was superior in the treatment of larger and multifocal tumors. Durability data has yet to mature but is promising given the higher predicted 1-year recurrence scores for patients in the VesiGel 0.12% group.

Funding

UroGen Pharma, Ra'anana, Israel