This protocol covers upper urinary tract urothelial carcinoma at an advanced or metastatic stage in a specific patient subset: those with PD-L1–positive tumours who are ineligible for platinum-based combination chemotherapy — whether due to a glomerular filtration rate below 30 ml/min, an ECOG performance status greater than 2, or grade greater than 2 comorbidities — and who are also ineligible for enfortumab vedotin plus pembrolizumab combination therapy.
Patients in this group present with advanced or metastatic disease and are excluded from the most commonly used first-line regimens. PD-L1 positivity is the key eligibility criterion that opens an alternative treatment pathway for this population.
For patients meeting these criteria, the first-line approach is guided by PD-L1 status and involves immune checkpoint inhibition. Should the disease progress, the protocol defines specific subsequent-line options — including an antibody-drug conjugate for patients with prior PD-1/PD-L1 inhibitor exposure, a targeted therapy for those harbouring certain molecular alterations, and further alternatives when preferred options are not feasible.
The full sequence, individual agent selection, and eligibility criteria for each line are defined in the complete structured protocol.
DOI: 10.1016/j.eururo.2025.02.023