Background/Objectives: The therapeutic landscape of advanced or metastatic urothelial carcinoma (UC) has shifted from platinum chemotherapy to precision immuno-oncology. Immune checkpoint inhibitors (ICIs)—pembrolizumab, nivolumab, and avelumab—show efficacy across platinum-refractory, maintenance, and adjuvant settings, yet benefit is limited to subsets, underscoring the need for biomarkers. Antibody–drug conjugates (ADCs), notably enfortumab vedotin(EV), and targeted agents such as FGFR inhibitors further expand options. This review synthesizes current evidence and emerging paradigms to guide combinations and sequencing. Methods: We performed a narrative synthesis of peer-reviewed trials (emphasizing pivotal phase III studies), key translational investigations, and contemporary guidelines on ICIs, ADCs, HER2-directed therapies, FGFR inhibitors, molecular subtyping, and genomic profiling in UC, integrating efficacy signals, biomarker associations, and practical implications for sequencing. Results: ICIs now occupy multiple settings, but heterogeneous benefit highlights the importance of molecularly informed selection. EV alone and with pembrolizumab has produced unprecedented first-line activity, prompting a strategic shift. Molecular subtyping and genomic profiling delineate phenotypes with variable immune responsiveness and targetable vulnerabilities, enabling rational combinations and refined sequencing. Ongoing trials are evaluating next-generation ADCs, HER2-directed approaches, and dual checkpoint blockade to achieve durable, personalized disease control. Conclusions: Management of locally advanced or metastatic UC is converging on precision immuno-oncology, wherein biomarker-driven selection, molecular subtyping, and thoughtful sequencing of ICIs, ADCs, and targeted agents are central to optimizing outcomes. Active trials and translational advances are expected to refine personalized strategies and embed molecular guidance into routine care.
背景/目的：晚期或转移性尿路上皮癌（UC）的治疗格局已从铂类化疗转向精准免疫肿瘤学。免疫检查点抑制剂（ICIs）——帕博利珠单抗、纳武利尤单抗和阿维鲁单抗——在铂类耐药、维持治疗及辅助治疗等场景中均显示出疗效，但其获益仅限于部分患者，这凸显了生物标志物的重要性。抗体偶联药物（ADCs），尤其是enfortumab vedotin（EV），以及FGFR抑制剂等靶向药物进一步拓展了治疗选择。本综述整合当前证据与新兴范式，以指导联合治疗与用药顺序策略。 方法：我们对经同行评议的临床试验（重点关注关键性III期研究）、重要转化研究以及关于UC中ICIs、ADCs、HER2靶向治疗、FGFR抑制剂、分子分型和基因组谱分析的现行指南进行了叙述性综合，整合了疗效信号、生物标志物关联以及用药顺序的实际意义。 结果：ICIs目前已应用于多种治疗场景，但其疗效的异质性凸显了基于分子特征进行选择的重要性。EV单药及与帕博利珠单抗联合方案在一线治疗中展现出前所未有的活性，推动了治疗策略的转变。分子分型和基因组谱分析能够区分具有不同免疫应答特征和可靶向弱点的表型，从而为合理的联合治疗和精细化的用药顺序提供依据。正在进行的临床试验正在评估新一代ADCs、HER2靶向疗法及双检查点阻断策略，以期实现持久、个性化的疾病控制。 结论：局部晚期或转移性UC的治疗正趋向于精准免疫肿瘤学，其中生物标志物驱动的选择、分子分型以及对ICIs、ADCs和靶向药物的审慎用药顺序是优化治疗结局的核心。积极的临床试验和转化医学进展有望进一步完善个体化策略，并将分子指导融入常规诊疗。
肿瘤(癌症)患者之家