Escobar Domenique, Wang Christopher, Suboc Noah, D'Souza Anishka, Tulpule Varsha
Catherine and Joseph Aresty Department of Urology, University of Southern California, Los Angeles, CA 90089, USA.
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90007, USA.
Cancers (Basel). 2025 Jul 25;17(15):2467. doi: 10.3390/cancers17152467.
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. A narrative review was conducted synthesizing evidence from guideline-based recommendations, retrospective and prospective clinical studies, and ongoing trials focused on UTUC. 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. 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.
上尿路尿路上皮癌（UTUC）是尿路上皮恶性肿瘤中一种罕见且生物学特性独特的亚型，约占尿路上皮癌的5%-10%。UTUC存在独特的诊断和治疗挑战，与膀胱癌相比，其在初诊时侵袭性疾病的可能性更高，预后也更差。目前UTUC的治疗策略很大程度上源自膀胱癌研究，这凸显了针对UTUC开展研究的必要性。本综述全面概述了UTUC，涵盖诊断方法、全身和腔内治疗、手术管理及未来方向。通过对基于指南的推荐、回顾性和前瞻性临床研究以及针对UTUC的正在进行的试验的证据进行综合分析，进行了一项叙述性综述。由于术后肾功能损害可能会妨碍辅助性顺铂的使用，基于顺铂的新辅助化疗在UTUC中越来越受到青睐。手术管理包括保留肾的方法和根治性肾输尿管切除术（RNU），其选择由肿瘤风险和患者合并症决定。虽然内镜治疗（EM）可保留肾功能，但它具有更高的复发率和监测负担；RNU仍是高危病例的标准治疗方法。晚期和转移性UTUC的全身治疗与膀胱尿路上皮癌相似。在EV-302试验中，恩沃利单抗（EV）联合帕博利珠单抗显示出优于化疗的疗效，在包括UTUC在内的各亚组中，缓解率、无进展生存期和总生存期均有所改善。对于不符合EV治疗条件的患者，CheckMate-901研究支持使用吉西他滨、顺铂和纳武利尤单抗进行一线化疗免疫治疗。进一步的全身治疗策略包括化疗后使用阿维鲁单抗维持治疗（JAVELIN Bladder 100）、针对FGFR2/3改变和HER2阳性疾病分别使用厄达替尼（THOR试验）和曲妥珠单抗德鲁替康（DESTINY-PanTumor02）等靶向治疗。从历史上看，UTUC的治疗格局是从膀胱癌推断而来的；然而，目前针对UTUC的研究正在得出更精确的治疗方案，包括使用免疫检查点抑制剂、抗体药物偶联物和生物标志物驱动的疗法。
