Immunotherapy for Upper Tract Urothelial Carcinomas: A 2026 Update

Upper tract urothelial carcinoma (UTUC) accounts for approximately 5-10% of diagnosed urothelial carcinoma (UC). Due to advanced initial presentation or aggressive progression of UTUC, the majority of patients will need systematic treatment in the neo-adjuvant or adjuvant setting. The management of patients with UTUC is complicated due to the lack of published data and only limited studies addressing immunotherapy in UTUC patients are available. The perioperative scenario in localized high-risk disease is still evolving. For metastatic disease, two monoclonal antibodies targeting PD-1 (pembrolizumab and nivolumab) and three to its ligand PD-L1 (atezolizumab, avelumab and durvalumab) have obtained approval for the second-line treatment of platinum-pretreated patients. Atezolizumab and pembrolizumab are currently approved in the first-line setting for cisplatin ineligible patients, with PD-L1- positive tumors. The aim of this review was to highlight the role of immunotherapy in locally advanced and metastatic UTUC and provide the safety profile of these regimens.