University of Iowa, Department of Urology, Iowa City, Iowa, USA.
University of Cologne, Department of Urology, Cologne, Germany.
Curr Opin Urol. 2021 May 1;31(3):178-187. doi: 10.1097/MOU.0000000000000863.
Although radical cystectomy represents the gold standard treatment for patients with high-risk nonmuscle invasive bladder cancer (NMIBC) whose disease does not respond to bacillus Calmette-Guérin (BCG), many patients are unable or unwilling to undergo surgery. The need remains for effective bladder-preserving therapies. This review aims to describe existing treatments, contemporary research in this field and ongoing trials of salvage therapies for patients with BCG-unresponsive NMIBC.
Intravesical chemotherapy has been utilized frequently in this setting. Emerging data on combination regimens such as intravesical gemcitabine and docetaxel and intravesical cabazitaxel, gemcitabine and cisplatin are promising; nevertheless, larger, prospective trials are needed. Meanwhile, the intravenous checkpoint inhibitor pembrolizumab was recently FDA-approved for patients BCG-unresponsive NMIBC. Encouraging clinical trial results for intravesical nadofaragene firadenovec, oportuzumab monatox and ALT-803 + BCG have been released, while data from trials of other treatment strategies, including novel chemotherapy and drug delivery, augmented BCG immunotherapy, adenoviral and gene therapy, targeted therapy, and combination systemic immunotherapy with intravesical agents, are eagerly awaited.
Several novel salvage therapies offer promise for patients with BCG-unresponsive NMIBC. Patient selection, efficacy, safety, cost and ease of administration must be carefully considered to determine the optimal treatment approach.
尽管根治性膀胱切除术是治疗高危非肌肉浸润性膀胱癌（NMIBC）患者的金标准，这些患者对卡介苗（BCG）治疗无反应，但许多患者无法或不愿接受手术。因此，仍需要有效的保膀胱治疗方法。本文旨在描述现有的治疗方法、该领域的最新研究以及用于治疗 BCG 无反应性 NMIBC 患者的挽救治疗的临床试验。
在这种情况下，经常使用膀胱内化疗。联合方案（如膀胱内吉西他滨联合多西他赛和卡巴他赛、吉西他滨联合顺铂）的新数据很有前景，但仍需要更大规模的前瞻性试验。同时，静脉注射检查点抑制剂派姆单抗最近被 FDA 批准用于治疗 BCG 无反应性 NMIBC 患者。膀胱内纳武单抗、奥普妥珠单抗单药和 ALT-803+BCG 的临床试验结果令人鼓舞，而其他治疗策略（包括新型化疗和药物输送、增强的 BCG 免疫治疗、腺病毒和基因治疗、靶向治疗以及联合全身免疫治疗与膀胱内药物）的临床试验数据正在等待中。
几种新的挽救治疗方法为 BCG 无反应性 NMIBC 患者带来了希望。必须仔细考虑患者选择、疗效、安全性、成本和给药便利性，以确定最佳治疗方法。
