Radical nephroureterectomy with en bloc bladder cuff excision and regional lymphadenectomy is the gold standard for the management of high-grade and high-risk upper tract urothelial carcinomas. There are a few prospective randomized controlled studies in this uncommon and often aggressive disease to support level-1 management guidelines. However, recent developments in imaging, minimally invasive techniques, lymphatic dissemination, and bladder cancer prevention raise the hope for improved risk stratification and treatments without compromising, and hopefully improving, oncological outcomes. Multimodality approaches in terms of neoadjuvant, adjuvant topical, and systemic chemotherapeutic regimens are promising, with 2 prospective trials either open or in development.
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