2024年美国食品和药物管理局批准erdafitinib用于治疗FGFR3改变的转移性尿路上皮癌（mUC），开启了膀胱癌靶向治疗的时代。在这篇综述中，我们总结了 FGFR 通路改变对肿瘤发生的影响、支持 FGFR 抑制剂治疗膀胱癌的临床数据以及仍然存在的挑战。1995 年至 2024 年间与 FGFR 抑制剂治疗尿路上皮癌相关的原始文章在PubMed 和 MEDLINE 数据库使用搜索词“FGFR”和“膀胱癌”。召集了一个在 FGFR 抑制剂治疗方面拥有丰富经验的国际专家小组来综合撰写一份协作性叙述性综述。高达 70% 的低级别非肌层浸润性膀胱癌中发现体细胞 FGFR3 改变；这些激活下游信号级联并最终导致细胞增殖。除了与低级别/低阶段肿瘤的联系外，这些改变是否会带来癌症复发或进展的预后风险几乎没有一致性。 FGFR3 改变的肿瘤与非炎症性肿瘤微环境有关，但矛盾的是，它似乎并不影响对全身免疫治疗的反应。几种泛 FGFR 抑制剂已在 mUC 中进行了研究。随着新型膀胱内给药系统的推出，FGFR 抑制剂有望改变早期 UC 的治疗格局。随着对膀胱癌生物学的深入了解、新的诊断方法和改进的给药方法，我们认为 FGFR 抑制剂将改变早期 UC 的治疗前景。引领膀胱癌精准治疗的发展。版权所有 © 2024 欧洲泌尿外科协会。由 Elsevier B.V. 出版。保留所有权利。

The 2024 US Food and Drug Administration approval of erdafitinib for the treatment of metastatic urothelial carcinoma (mUC) with FGFR3 alterations ushered in the era of targeted therapy for bladder cancer. In this review, we summarize the effects of FGFR pathway alterations in oncogenesis, clinical data supporting FGFR inhibitors in the management of bladder cancer, and the challenges that remain.Original articles relevant to FGFR inhibitors in urothelial cancer between 1995 and 2024 were systematically identified in the PubMed and MEDLINE databases using the search terms "FGFR" and "bladder cancer". An international expert panel with extensive experience in FGFR inhibitor treatment was convened to synthesize a collaborative narrative review.Somatic FGFR3 alterations are found in up to 70% of low-grade non-muscle-invasive bladder cancers; these activate downstream signaling cascades and culminate in cellular proliferation. Beyond a link to lower-grade/lower-stage tumors, there is little consistency regarding whether these alterations confer prognostic risks for cancer recurrence or progression. FGFR3-altered tumors have been linked to a non-inflamed tumor microenvironment, but paradoxically do not seem to impact the response to systemic immunotherapy. Several pan-FGFR inhibitors have been investigated in mUC. With the introduction of novel intravesical drug delivery systems, FGFR inhibitors are poised to transform the therapeutic landscape for early-stage UC.With deepening understanding of the biology of bladder cancer, novel diagnostics, and improved drug delivery methods, we posit that FGFR inhibition will lead the way in advancing precision treatment of bladder cancer.Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.