Endoscopic balloon cryoablation against single instillation after transurethral resection of bladder cancer: A multicenter, randomized, controlled noninferiority trial.

Abstract

e16561 Background: Cryotherapy is a prevalent percutaneous ablative therapy for solid tumors. However, studies on the clinical practice of endoscopic cryotherapy for intraluminal malignancies are lacking. We aim to explore the feasibility of endoscopic cryotherapy for bladder cancer. Methods: In this multicenter, randomized, parallel controlled, non-inferiority trial, we compared endoscopic balloon cryoablation (EBCA) with a single instillation (SI) of pirarubicin after transurethral resection (TUR).Men or women aged 18-85 years with a clinical diagnosis of bladder cancer (tumor number no more than 3 and maximal tumor size no more than 3 cm) were included. The exclusion criteria were as follows: locally advanced urinary bladder cancer (clinical stage T3 or T4), lymph node involvement (N1) or distant metastasis (M1), severe organ dysfunction, severe coagulation disorder, sepsis, concomitant neoplastic malignancy and other conditions unsuitable for surgery or intravesical chemotherapy. Women in pregnancy or lactation were also excluded. Eligible participants were randomly assigned (1:1) to the TUR-EBCA or TUR-SI group. The primary endpoint was the residual-free rate at repeated TUR. A non-inferiority test was used to compare the primary endpoint with a chosen margin of 10%. The secondary endpoints included the recurrence-free survival (RFS), progression-free survival (PFS) and adverse events. Results: We recruited 227 participants between November, 2017, and September, 2020. In total, 205 patients received EBCA or SI after TUR, of whom 163 completed all the required interventions and follow-up. In the per-protocol analyses, 75 (91.5%) of 82 patients had no residual tumor in the TUR-EBCA group compared with 61 (76.5%) of 81 in the TUR-SI group (risk difference 14.9%; 95% confidence interval [CI] 0.03 to 0.27, P < 0.001), meeting the criteria for non-inferiority. Similar results were found in the after intention-to-treat analysis. After a median follow-up of 21 months, the TUR-EBCA group had better RFS(HR = 0.49; 95% confidence interval [CI] 0.24 to 0.99; Log-rank P = 0.046) and PFS (HR = 0.25; 95% confidence interval [CI] 0.08 to 0.77; Log-rank P = 0.0092). There were no significant differences in the SAEs rate (3.0% vs. 3.9%, p = 0.52). Conclusions: EBCA is a safe and effective adjuvant alternative to TUR for bladder cancer with the potential advantage of “energetically resecting” the tumor base. Clinical trial information: NCT02760953.