This is a prospective, multicentre, single-arm phase II study evaluating a response-adapted kidney-preserving strategy in patients with HER2-positive high-risk upper tract urothelial carcinoma (UTUC). Patients will receive neoadjuvant disitamab vedotin plus tislelizumab, followed by response-adapted local treatment, including kidney-sparing surgery or radical nephroureterectomy based on predefined criteria.
The primary objective is to assess whether this multimodal strategy can achieve clinically meaningful oncologic control while preserving renal function, as measured by 1-year kidney-intact event-free survival (KI-EFS). Secondary and exploratory objectives include evaluation of clinical response, survival outcomes, safety, renal function preservation, and longitudinal dynamics of circulating and urinary tumor DNA.
Age ≥18 years at the time of informed consent.
Histologically confirmed upper tract urothelial carcinoma (UTUC) arising from the renal pelvis or ureter, based on ureteroscopic biopsy.
High-risk UTUC, defined by at least one of the following features: Tumour size ≥2 cm; High-grade cytology or biopsy; Radiographic evidence of local invasion (≥cT2); Hydronephrosis; Multifocal disease
Clinical stage cT1-T3, N0-N1, M0, based on radiographic assessment.
Evidence of distant metastatic disease (M1).
Unresectable or bulky nodal disease (≥N2) not amenable to curative-intent surgery.
Prior systemic therapy for urothelial carcinoma, including:Chemotherapy; Immunotherapy; HER2-targeted therapy.
Prior radical nephroureterectomy for current disease.
RenJi Hospital
Lead sponsor
West China Hospital
Collaborator
Tianjin Medical University Second Hospital
Collaborator
Peking University First Hospital
Collaborator