Urothelial cell carcinoma (UCC, bladder cancer, BC) remains a difficult-to-treat malignancy with a rising incidence worldwide. In the U.S., UCC is the sixth most incident neoplasm and ~90% of diagnoses are made in those >55 years of age; it is ~four times more commonly observed in men than women. The most important risk factor for developing BC is tobacco smoking, which accounts for ~50% of cases, followed by occupational exposure to aromatic amines and ionizing radiation. The standard of care for advanced UCC includes platinum-based chemotherapy and programmed cell death (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors, administered as frontline, second-line, or maintenance therapy. UCC remains generally incurable and is associated with intrinsic and acquired drug and immune resistance. UCC is lethal in the metastatic state and characterized by genomic instability, high PD-L1 expression, DNA damage-response mutations, and a high tumor mutational burden. Although immune checkpoint inhibitors (ICIs) achieve long-term durable responses in other cancers, their ability to achieve similar results with metastatic UCC (mUCC) is not as well-defined. Here, we discuss therapies to improve UCC management and how comprehensive tumor profiling can identify actionable biomarkers and eventually fulfill the promise of precision medicine for UCC patients.
尿路上皮细胞癌（UCC，膀胱癌，BC）是一种治疗难度较高的恶性肿瘤，全球发病率持续上升。在美国，UCC是第六大常见肿瘤，约90%的确诊患者年龄超过55岁；男性发病率约为女性的四倍。膀胱癌最重要的风险因素是吸烟，约占病例的50%，其次是职业性接触芳香胺和电离辐射。晚期UCC的标准治疗方案包括铂类化疗以及程序性细胞死亡蛋白-1（PD-1）或程序性细胞死亡配体-1（PD-L1）抑制剂，可作为一线、二线或维持治疗。UCC通常仍无法治愈，且与内在及获得性的药物和免疫耐药性相关。转移性UCC具有致命性，其特征包括基因组不稳定性、高PD-L1表达、DNA损伤反应突变和高肿瘤突变负荷。尽管免疫检查点抑制剂（ICIs）在其他癌症中能实现长期持久的疗效，但其在转移性UCC（mUCC）中达到类似效果的能力尚不明确。本文探讨了改善UCC治疗的策略，并阐述了全面肿瘤分析如何识别可操作的生物标志物，最终实现UCC患者精准医疗的前景。
Current and Emerging Strategies to Treat Urothelial Carcinoma
肿瘤(癌症)患者之家