Background/Objectives:Upper tract urothelial carcinoma (UTUC) is a rare and biologically distinct subset of urothelial malignancies, comprising approximately 5–10% of urothelial cancers. UTUC presents unique diagnostic and therapeutic challenges, with both a higher likelihood of invasive disease at presentation and a less favorable prognosis compared to urothelial carcinoma of the bladder. Current treatment strategies for UTUC are largely derived from bladder cancer studies, underscoring the need for UTUC-directed research. This review provides a comprehensive overview of UTUC, encompassing diagnostic approaches, systemic and intraluminal therapies, surgical management, and future directions.Methods:A narrative review was conducted synthesizing evidence from guideline-based recommendations, retrospective and prospective clinical studies, and ongoing trials focused on UTUC.Results:Neoadjuvant cisplatin-based chemotherapy is increasingly preferred in UTUC due to the risk of postoperative renal impairment that may preclude adjuvant cisplatin use. Surgical management includes kidney-sparing approaches and radical nephroureterectomy (RNU), with selection guided by tumor risk and patient comorbidities. While endoscopic management (EM) preserves renal function, it carries a higher recurrence and surveillance burden; RNU remains standard for high-risk cases. Systemic therapy for advanced and metastatic UTUC mirrors that of bladder urothelial carcinoma. Enfortumab vedotin (EV) plus pembrolizumab showed superior efficacy over chemotherapy in the EV-302 trial, with improved response rate, progression-free survival, and overall survival across subgroups, including UTUC. For patients ineligible for EV, the CheckMate-901 study supported first-line chemoimmunotherapy with gemcitabine, cisplatin, and nivolumab. Further systemic therapy strategies include maintenance avelumab post-chemotherapy (JAVELIN Bladder 100), targeted therapies such as erdafitinib (THOR trial), and trastuzumab deruxtecan (DESTINY-PanTumor02) in FGFR2/3-altered and HER2-positive disease, respectively.Conclusions:Historically, the therapeutic landscape of UTUC has been extrapolated from bladder cancer; however, ongoing research specific to UTUC is deriving more precise regimens involving the use of immune checkpoint inhibitors, antibody–drug conjugates, and biomarker-driven therapies.
背景/目的：上尿路尿路上皮癌（UTUC）是一种罕见且具有独特生物学特征的尿路上皮恶性肿瘤亚型，约占所有尿路上皮癌的5-10%。与膀胱尿路上皮癌相比，UTUC在诊断时侵袭性病变的可能性更高，预后也相对较差，这为其诊断和治疗带来了独特的挑战。目前UTUC的治疗策略主要借鉴于膀胱癌的研究，这凸显了开展针对UTUC研究的必要性。本综述旨在全面概述UTUC，涵盖诊断方法、全身及腔内治疗、外科管理以及未来发展方向。 方法：本文采用叙述性综述方法，综合了基于指南的建议、回顾性和前瞻性临床研究以及针对UTUC的正在进行中的试验证据。 结果：由于术后肾功能损伤可能影响辅助顺铂的使用，新辅助顺铂化疗在UTUC治疗中日益受到青睐。外科管理包括保留肾脏的手术和根治性肾输尿管切除术（RNU），具体选择取决于肿瘤风险和患者合并症。虽然内镜治疗（EM）能保留肾功能，但其复发率和后续监测负担较高；对于高风险病例，RNU仍是标准治疗。晚期和转移性UTUC的全身治疗与膀胱尿路上皮癌相似。EV-302试验显示，enfortumab vedotin（EV）联合帕博利珠单抗在包括UTUC在内的各亚组中，其疗效优于化疗，表现为更高的缓解率、更长的无进展生存期和总生存期。对于不适合EV治疗的患者，CheckMate-901研究支持使用吉西他滨、顺铂联合纳武利尤单抗作为一线化疗免疫治疗方案。进一步的全身治疗策略包括化疗后avelumab维持治疗（JAVELIN Bladder 100研究），以及针对特定靶点的治疗，例如分别用于FGFR2/3基因改变和HER2阳性疾病的erdafitinib（THOR试验）和trastuzumab deruxtecan（DESTINY-PanTumor02研究）。 结论：历史上，UTUC的治疗方案多从膀胱癌外推而来；然而，目前针对UTUC的持续研究正在制定更精确的治疗方案，涉及免疫检查点抑制剂、抗体偶联药物以及生物标志物驱动的疗法。
Diagnosis and Management of Upper Tract Urothelial Carcinoma: A Review
肿瘤(癌症)患者之家