Endoscopic balloon cryoablation plus transurethral resection for bladder cancer: A phase 2, multicenter, randomized, controlled trial.

ABSTRACT

BACKGROUND: Cryotherapy is a prevalent percutaneous ablative therapy for solid tumors. Here, we report a novel device using liquid nitrogen for endoscopic cryotherapy of bladder cancer. METHODS: In this multicenter, randomized, parallel controlled, Phase 2 trial, we compared endoscopic balloon cryoablation (EBCA) with a single instillation (SI) of pirarubicin after transurethral resection (TUR). Eligible participants were randomly assigned (11) to the TUR-EBCA or TUR-SI group. Repeat TUR or tissue biopsies were performed to evaluate residual tumor at 4 to 6 weeks after primary treatment. The primary end point was the local control rate. The secondary end points included the tumor upgrading/upstaging, catheter indwelling duration, and adverse events. RESULTS: In total, 205 patients received EBCA or SI after TUR between November 2017 and September 2020, of whom 163 completed all the required interventions. In the per-protocol set, the local control rate was 91.5% (75/82) in TUR-EBCA group compared with 76.5% (61/81) in TUR-SI group (risk difference, 15%; 95% CI, 0.03-0.27, p < .001), meeting the criteria for noninferiority. Similar results were found in the modified intention-to-treat analysis. Tumor upgrading/upstaging was found in five patients from the TUR-SI group. There was no significant difference in the catheter indwelling duration (5.1 vs. 5.2 days, p = .76) or serious adverse event rate (3.0% vs. 3.9%, p = .52). The median follow-up time of post hoc analysis was 31 (range, 15-50) months. Patients in the TUR-EBCA group had a better recurrence-free survival and progression-free survival. CONCLUSION: EBCA is a safe and effective adjuvant therapy with TUR for non-muscle-invasive bladder cancer. PLAIN LANGUAGE SUMMARY: This is the first randomized trial that evaluated endoscopic cryotherapy after transurethral resection (TUR) of bladder tumors. The efficacy and safety analysis shows endoscopic balloon cryoablation (EBCA) is a promising alternative. Results report that EBCA is not inferior to a single instillation of intravesical chemotherapy in eliminating residual bladder tumor. Further analysis with ∼3 years' median follow-up suggested a better prognosis in patients who received EBCA after TUR.