A Comparative Study of Neoadjuvant Chemotherapy Versus Upfront Radical Surgery for Upper Tract Urothelial Carcinoma

Inclusion criteria

• Histologically confirmed upper tract urothelial carcinoma (UTUC). For mixed histology, urothelial carcinoma must be the predominant component (≥50%).
• Clinically non-metastatic disease (cN≤1, M0) as determined by cross-sectional imaging (CT or MRI of chest/abdomen/pelvis).
• Planned treatment with radical nephroureterectomy (RNU).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate renal function, defined as glomerular filtration rate (GFR) ≥ 45 mL/min, making the patient a potential candidate for cisplatin-based neoadjuvant chemotherapy.
• Adequate organ and bone marrow function as determined by standard screening tests.
• Recovery from all reversible toxicities of any prior surgery.
• Age ≥ 18 years at the time of enrollment.
• Ability to understand the study and provide signed informed consent.

Exclusion criteria

• Radiographic evidence of ≥cN2 lymph node disease or distant metastases (M1).
• History of invasive, lymph node-positive, or metastatic urothelial carcinoma within 2 years prior to enrollment, or history of invasive contralateral UTUC.
• Presence of only a solitary kidney or cisplatin ineligibility.
• Concurrent participation in another interventional clinical trial at the time of enrollment.
• History of a non-urothelial malignant tumor unless the patient has been disease-free for at least 1 year (exceptions include adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix).
• Pregnancy or lactation. Women and men of reproductive potential must agree to use effective contraception.
• Any other medical condition, comorbidity, or psychiatric illness that, in the investigator's judgment, would make the patient an unsuitable candidate for the study.