Department of Urology, St. Josef Medical Center, University of Regensburg, Landshuterstrasse 65, 93053, Regensburg, Germany.
Center for Statistics and Clinical Studies, University of Regensburg, Regensburg, Germany.
World J Urol. 2021 Oct;39(10):3799-3805. doi: 10.1007/s00345-021-03719-0. Epub 2021 May 17.
Photodynamic diagnosis and white-light TURB with adjuvant intravesical chemotherapy (ICT) is widely used in treatment of bladder cancer. This non-inferiority trial is designed to demonstrate non-inferiority regarding recurrence-free survival (RFS) of Hexvix TURB followed by immediate instillation compared to white-light TURB with immediate instillation followed by maintenance ICT.
Between 07/2010 and 12/2016, 129 patients with EORTC intermediate risk non-muscle invasive bladder cancer treated with TURB were included in this multicentre phase III study. Patients were randomized and received either white-light TURB with immediate ICT followed by maintenance ICT (n = 62, 20 mg Mitomycin weekly for 6 weeks as induction phase, afterwards 20 mg/month for 6 months) or Hexvix TURB with immediate ICT only (n = 67, 40 mg Mitomycin). Primary study endpoint was RFS after 12 months. Hexvix TURB was counted as non-inferior to white light alone if the upper limit of the one-sided 95% confidence interval of hazard ratio was lower than 1.676. Due to the non-inferiority design, the per-protocol population was used as the primary analysis population (n = 113) RESULTS: Median follow-up was 1.81 years. Hexvix group showed more events (recurrence or death) than white-light group (19 vs. 10) resulting in a HR of 1.29 (upper limit of one-sided 95%-CI = 2.45; p = 0.249). The ITT population yielded similar results (HR = 1.67); 3.18], p = 0.493). There was no significant difference in overall survival between both groups (p = 0.257).
Non-inferiority of Hexvix TURB relative to white-light TURB with maintenance Mitomycin instillation in intermediate risk urothelial carcinoma of the bladder was not proven. Hence a higher effect of maintenance ICT is to assume compared to a Hexvix-improved TURB only, confirming its important role in patient treatment.
光动力诊断和白光 TURB 联合辅助膀胱内化疗（ICT）广泛用于膀胱癌的治疗。本非劣效性试验旨在证明 Hexvix TURB 即刻灌注后无复发生存率（RFS）不劣于白光 TURB 即刻灌注后即刻 ICT 联合维持 ICT。
2010 年 7 月至 2016 年 12 月，129 例 EORTC 中危非肌层浸润性膀胱癌患者接受 TURB 治疗，纳入这项多中心 III 期研究。患者随机分为两组，一组接受白光 TURB 即刻 ICT 联合维持 ICT（n=62，诱导期每周给予 20mg 丝裂霉素，共 6 周，然后每月给予 20mg，共 6 个月），另一组接受 Hexvix TURB 即刻 ICT（n=67，40mg 丝裂霉素）。主要研究终点为 12 个月时的 RFS。如果单侧 95%置信区间上限的危害比低于 1.676，则认为 Hexvix TURB 优于单纯白光 TURB。由于非劣效性设计，采用方案人群作为主要分析人群（n=113）。
中位随访时间为 1.81 年。Hexvix 组的事件（复发或死亡）多于白光组（19 例 vs. 10 例），HR 为 1.29（单侧 95%CI 上限为 2.45；p=0.249）。ITT 人群得出相似结果（HR=1.67；95%CI 上限为 2.45；p=0.249）。两组的总生存率无显著差异（p=0.257）。
在中危尿路上皮癌中，Hexvix TURB 相对于白光 TURB 联合维持丝裂霉素灌注的非劣效性未得到证实。因此，与单纯 Hexvix TURB 相比，维持 ICT 的效果更高，这证实了其在患者治疗中的重要作用。
