尽管最近取得了进展，但晚期尿路上皮癌 (aUC) 仍然无法治愈，5 年生存率约为 10%。对于大多数 aUC 患者来说，铂类化疗作为一线治疗发挥着重要作用。抗 PD-L1 抗体 avelumab 被批准作为铂类化疗后未出现初始疾病进展的患者的维持治疗，这是一项重要的进展，改善了该疾病患者的生存结果。除此之外，针对 PD-1 或​​ PD-L1 的一线免疫检查点抑制剂 (ICIs) 的使用仅限于不适合接受含铂化疗方案的患者。其他重要进展包括 FDA 加速批准一线 enfortumab vedotin 联合 pembrolizumab 用于不适合接受顺铂治疗的患者，以及 FGFR 抑制剂、enfortumab vedotin 和 sacituzumab govitecan 可用于后续治疗。一些研究问题仍未得到解决，包括缺乏足够的生物标志物、如何优先考虑个体患者的不同治疗方案以及哪些药物可以作为单一疗法有效。随着抗体药物缀合物类药物、下一代 ICI、双特异性抗体和细胞疗法等模式的出现，未来充满希望。在这篇综述中，我们总结了 aUC 患者全身治疗的进展，并提供了对未满足需求的见解。© 2023。Springer Nature Limited。

Despite recent advances, advanced-stage urothelial carcinoma (aUC) remains incurable, with 5-year survival rates of approximately 10%. Platinum-based chemotherapy has a major role as first-line therapy for most patients with aUC. The approval of the anti-PD-L1 antibody avelumab as maintenance therapy for patients without initial disease progression on platinum-based chemotherapy is an important development that has improved the survival outcomes of patients with this disease. Otherwise, the use of first-line immune-checkpoint inhibitors (ICIs) targeting PD-1 or PD-L1 has been restricted to patients who are ineligible for platinum-containing chemotherapy regimens. Other important developments include the FDA-accelerated approval of first-line enfortumab vedotin plus pembrolizumab for patients ineligible to receive cisplatin and the availability of FGFR inhibitors, enfortumab vedotin and sacituzumab govitecan for subsequent lines of therapy. Several research questions remain unaddressed including the lack of adequate biomarkers, how to assign priority to the different treatment options for individual patients and which agents can be effective as monotherapies. The future is promising with the emergence of modalities such as antibody-drug conjugate-like drugs, next-generation ICIs, bispecific antibodies and cellular therapies. In this Review, we summarize the evolution of systemic therapy for patients with aUC and provide insights into the unmet needs.© 2023. Springer Nature Limited.