Department of Urology, Ichan School of Medicine at the Mount Sinai Hospital, New York, NY 10029, USA.
CUNY School of Medicine, City College of New York, New York, NY 10031, USA.
Curr Oncol. 2024 Feb 16;31(2):1063-1078. doi: 10.3390/curroncol31020079.
Bladder cancer is a heterogeneous disease. Treatment decisions are mostly decided based on disease stage (non-muscle invasive or muscle invasive). Patients with muscle-invasive disease will be offered a radical treatment combined with systemic therapy, while in those with non-muscle-invasive disease, an attempt to resect the tumor endoscopically will usually be followed by different intravesical instillations. The goal of intravesical therapy is to decrease the recurrence and/or progression of the tumor. In the current landscape of bladder cancer treatment, BCG is given intravesically to induce an inflammatory response and recruit immune cells to attack the malignant cells and induce immune memory. While the response to BCG treatment has changed the course of bladder cancer management and spared many "bladders", some patients may develop BCG-unresponsive disease, leaving radical surgery as the best choice of curative treatment. As a result, a lot of effort has been put into identifying novel therapies like systemic pembrolizumab and Nadofaragene-Firadenovac to continue sparing bladders if BCG is ineffective. Moreover, recent logistic issues with BCG production caused a worldwide BCG shortage, re-sparking interest in alternative BCG treatments including mitomycin C, sequential gemcitabine with docetaxel, and others. This review encompasses both the historic and current role of BCG in the treatment of non-muscle-invasive bladder cancer, revisiting BCG alternative therapies and reviewing the novel therapeutics that were approved for the BCG-unresponsive stage or are under active investigation.
膀胱癌是一种异质性疾病。治疗决策主要基于疾病阶段(非肌肉浸润性或肌肉浸润性)来决定。患有肌肉浸润性疾病的患者将接受联合系统治疗的根治性治疗,而患有非肌肉浸润性疾病的患者,通常会尝试通过内镜切除肿瘤,然后进行不同的膀胱内灌注。膀胱内治疗的目的是降低肿瘤的复发和/或进展。在当前的膀胱癌治疗格局中,BCG 通过诱导炎症反应和招募免疫细胞来攻击恶性细胞并诱导免疫记忆,从而被膀胱内给药。虽然 BCG 治疗的反应改变了膀胱癌管理的进程,并使许多“膀胱”得以保留,但一些患者可能会发展出对 BCG 无反应的疾病,使根治性手术成为最佳的治愈性治疗选择。因此,人们投入了大量精力来寻找新的治疗方法,如系统 pembrolizumab 和 Nadofaragene-Firadenovac,如果 BCG 无效,继续保留膀胱。此外,最近 BCG 生产的物流问题导致全球 BCG 短缺,重新引起了对替代 BCG 治疗的兴趣,包括丝裂霉素 C、吉西他滨序贯多西他赛等。本综述涵盖了 BCG 在治疗非肌肉浸润性膀胱癌中的历史和当前作用,重新审视了 BCG 的替代治疗方法,并回顾了已批准用于 BCG 无反应期或正在积极研究中的新型治疗药物。
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