Introduction:

Low-grade intermediate-risk nonmuscle-invasive bladder cancer (LG IR NMIBC) is a chronic illness commonly treated by repetitive transurethral resection of bladder tumor (TURBT). We compared the efficacy and safety of intravesical chemoablation with UGN-102 (a reverse thermal gel containing mitomycin), with or without subsequent TURBT, to TURBT alone in patients with LG IR NMIBC.

Methods:

This prospective, randomized, Phase 3 trial recruited patients with new or recurrent LG IR NMIBC to receive initial treatment with either UGN-102 (75 mg mitomycin in 56 mL admixture with reverse thermal hydrogel to equal 1.33 mg/mL) once weekly for 6 weeks or TURBT. Patients were followed quarterly by endoscopy, cytology, and for-cause biopsy. The primary endpoint was disease-free survival (DFS). All patients were followed for adverse events.

Results:

Trial enrollment was halted by the sponsor to pursue an alternative development strategy after 282 of a planned 632 patients were randomized to UGN-102 ± subsequent TURBT (n=142) or TURBT monotherapy (n=140), rendering the trial underpowered to perform hypothesis testing. Patients were predominantly male and ≥65 years of age. Tumor-free complete response 3 months after initial treatment was achieved by 92 patients (65%) who received UGN-102 and 89 patients (64%) treated by TURBT. The estimated probability of DFS 15 months after randomization was 72% for UGN-102 ± TURBT and 50% for TURBT [hazard ratio 0.45]. The most common adverse events (incidence ≥10%) in the UGN-102 group were dysuria, micturition urgency, nocturia, and pollakiuria.

Conclusion:

Primary, non-surgical chemoablation with UGN-102 for the management of LG IR NMIBC offers a potential therapeutic alternative to immediate TURBT monotherapy and warrants further investigation.

Funding: UroGen Pharma