Treatment of Low-grade Intermediate-risk Nonmuscle-invasive Bladder Cancer With UGN-102 ± Transurethral Resection of Bladder Tumor Compared to Transurethral Resection of Bladder Tumor Monotherapy: A Randomized, Controlled, Phase 3 Trial (ATLAS)

Abstract

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

Materials and methods: This prospective, randomized, phase 3 trial recruited patients with new or recurrent low-grade intermediate-risk nonmuscle-invasive bladder cancer to receive initial treatment with either UGN-102 once weekly for 6 weeks or transurethral resection of bladder tumor. Patients were followed quarterly by endoscopy, cytology, and for-cause biopsy. The primary end point was disease-free survival. 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 transurethral resection of bladder tumor (n=142) or transurethral resection of bladder tumor 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 transurethral resection of bladder tumor. The estimated probability of disease-free survival 15 months after randomization was 72% for UGN-102 ± transurethral resection of bladder tumor and 50% for transurethral resection of bladder tumor (hazard ratio 0.45). The most common adverse events (incidence ≥10%) in the UGN-102 group were dysuria, micturition urgency, nocturia, and pollakiuria.

Conclusions: Primary, nonsurgical chemoablation with UGN-102 for the management of low-grade intermediate-risk nonmuscle-invasive bladder cancer offers a potential therapeutic alternative to immediate transurethral resection of bladder tumor monotherapy and warrants further investigation.

Trial registration: ClinicalTrials.gov NCT04688931.

Keywords: ablation techniques; clinical trial; mitomycin; non-muscle invasive bladder neoplasms; phase III.

Figure 1.

Study design. *Screening procedures were performed to provide evidence of low-grade disease and exclude high-grade disease. **Patients randomized to either treatment arm with residual low-grade disease at the 3-month assessment were eligible for treatment with transurethral resection of bladder tumor (TURBT). CR indicates complete response; CT, computed tomography; DFS, disease-free survival; EOS, end of study; EOT, end of treatment; MRI, magnetic resonance imaging; NCR, noncomplete response; TURBT, transurethral resection of bladder tumor.

Figure 2.

Patient flow diagram. AE indicates adverse event; CR, complete response; DFS, disease-free survival; EOS, end of study; HG, high-grade; ITT, intent-to-treat; LG, low-grade; TURBT, transurethral resection of bladder tumor.

Figure 3.

Kaplan-Meier estimates of disease-free survival (intent-to-treat analysis set). TURBT indicates transurethral resection of bladder tumor.

Figure 4.

Kaplan-Meier estimates of duration of response (3-month complete response [CR] analysis set). The 3-month CR analysis set includes those patients randomized to initial treatment with UGN-102 or transurethral resection of bladder tumor (TURBT) who were disease-free at the 3-month assessment.