This is a single-center, open-label, non-randomized controlled trial comparing the efficacy and safety of neoadjuvant chemotherapy (NAC) followed by radical surgery versus upfront radical surgery alone in patients with high-risk, non-metastatic upper tract urothelial carcinoma (UTUC).

The study aims to answer the following key questions:

Does NAC improve pathologic response rates (defined as downstaging to \

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.

The study population will consist of adult patients (≥18 years) with histologically confirmed, non-metastatic upper tract urothelial carcinoma (UTUC) who are planned for radical nephroureterectomy (RNU).

Participants will be recruited from the urology oncology clinics at a single tertiary care center (e.g., The First Affiliated Hospital of Naval Military Medical University). Eligibility will be determined based on predefined inclusion and exclusion criteria, focusing on patients with adequate renal function (GFR ≥45 mL/min) and performance status (ECOG 0-1) to be potential candidates for cisplatin-based chemotherapy.

The population will include both patients who are deemed eligible and choose to receive neoadjuvant chemotherapy prior to surgery and those who proceed directly to surgery.

Individual participant data (IPD) will not be shared to ensure the confidentiality and privacy of our study participants. The informed consent documents approved by our institutional ethics committee do not include provisions for public sharing of individual-level data. Furthermore, the data contains potentially identifiable sensitive health information, and sharing it would be inconsistent with our commitments to participants and the requirements of local data protection regulations.