Hilser Thomas, Darr Christopher, Bedke Jens, Ivanyi Philipp, Klümper Niklas, Eckstein Markus, Schlack Katrin, Grünwald Viktor
Department of Medical Oncology, West German Cancer Center, University Hospital Essen and German Cancer Consortium (DKTK), Essen, Germany.
Department of Urology, University Hospital Essen and German Cancer Consortium (DKTK), Essen, Germany.
Oncol Res Treat. 2025 Mar 26:1-8. doi: 10.1159/000545514.
Urothelial carcinoma (UC) is a significant global health burden and shows consistent increase in incidence. The treatment landscape for advanced or metastatic urothelial carcinoma (mUC) has evolved, but significant challenges remain to prolong survival. The article is based on the content of the recent guidelines and a selective literature search.
For many years in the past, cisplatin-based chemotherapy was the standard first-line therapy for eligible patients. But chemotherapy alone provides limited long-term benefit, and a large proportion of patients either progress rapidly or are ineligible for cisplatin due to comorbidities. This demonstrates the medical need and led to the development of immune checkpoint inhibitors and antibody-drug conjugates (ADCs) in the field of mUC treatment. More recently, the introduction of ADCs further enlarged the medical armamentarium in mUC patients and was further explored as combined regimens. The combination of enfortumab vedotin (EV) and pembrolizumab was superior to standard platin-based chemotherapy as did nivolumab plus gemcitabine with cisplatin, which permanently transformed the medical treatment landscape in mUC. Today, EV plus pembrolizumab is the first-line standard in treatment of therapeutic advanced or mUC. New options are also emerging, such as molecular therapies that target the fibroblast growth factor receptor. In the future, targeted therapy could also be used in the perioperative area.
Today, EV combined with pembrolizumab sets a new standard of care in medical treatment of a/mUC patients. Compared to platinum-based therapy, EV plus pembrolizumab doubled the overall survival probability and reported a median OS of 31.5 months, which is a new hallmark of palliative medical treatment in this disease. This novel therapy in combination with molecular therapies, novel devices, and molecular markers offers a great opportunity for the next step in medical development in localized UC, and its clinical applicability is being investigated in ongoing studies.
尿路上皮癌（UC）是一项重大的全球健康负担，且发病率持续上升。晚期或转移性尿路上皮癌（mUC）的治疗格局已有所演变，但在延长生存期方面仍存在重大挑战。本文基于近期指南内容及选择性文献检索。
在过去多年里，以顺铂为基础的化疗是符合条件患者的标准一线治疗方案。但单纯化疗提供的长期益处有限，且很大一部分患者要么进展迅速，要么因合并症而不符合使用顺铂的条件。这表明了医疗需求，并促使在mUC治疗领域开发免疫检查点抑制剂和抗体药物偶联物（ADC）。最近，ADC的引入进一步扩充了mUC患者的医疗手段，并作为联合方案得到进一步探索。恩杂鲁胺（EV）与帕博利珠单抗联合使用优于标准铂类化疗，纳武利尤单抗联合吉西他滨和顺铂也是如此，这永久性地改变了mUC的药物治疗格局。如今，EV加帕博利珠单抗是治疗晚期或mUC的一线标准方案。新的选择也在不断涌现，例如靶向成纤维细胞生长因子受体的分子疗法。未来，靶向治疗也可用于围手术期。
如今，EV联合帕博利珠单抗为a/mUC患者的药物治疗树立了新的护理标准。与铂类疗法相比，EV加帕博利珠单抗使总生存概率翻倍，报告的中位总生存期为31.5个月，这是该疾病姑息性药物治疗的一个新标志。这种新型疗法与分子疗法、新型设备和分子标志物相结合，为局限性UC的下一步医学发展提供了巨大机遇，其临床适用性正在正在进行的研究中进行调查。
