[Update: Evolution in the management of metastatic urothelial carcinomas]

Metastatic urothelial carcinoma is undergoing a major therapeutic transformation. The combination of enfortumab-vedotin and pembrolizumab, established in 2024 as the first-line standard of care, has demonstrated impressive survival benefits at 30 months of follow-up and is now the preferred regimen, regardless of cisplatin eligibility. Beyond enfortumab-vedotin, the development of antibody-drug conjugates opens up a field for rapid innovation: next-generation anti-nectin-4 agents, anti-TROP2 strategies, and anti-HER2 agents such as trastuzumab deruxtecan or disitamab vedotin, including in HER2-"low" disease. These compounds expand the range of actionable targets and illustrate the progressive integration of precision medicine into metastatic urothelial carcinoma. Targeted therapies are also gaining ground. Erdafitinib is now reimbursed in France for FGFR3-altered tumors, while more selective inhibitors (such as LOXO-435) are currently under investigation. In addition, novel approaches including bispecific antibodies and bicyclic peptides are being evaluated in early-phase trials, reflecting the dynamism of this evolving field. Altogether, metastatic urothelium carcinoma has become a paradigm of rapidly evolving oncology, driven by the emergence of antibodies-drug-conjugates, targeted therapies, and precision medicine, which are reshaping treatment standards and opening new clinical perspectives.