Neoadjuvant Chemotherapy Before Surgery vs Surgery Alone for UTUC: A Randomized Trial

Comparative Efficacy of Neoadjuvant Chemotherapy Versus Immediate Nephroureterectomy in the Treatment of Localized Upper Tract Urothelial Carcinoma: A Randomized Controlled Trial

This clinical trial aims to compare the effectiveness and safety of two treatment options for patients with high-risk upper tract urothelial carcinoma (UTUC). One group will receive neoadjuvant chemotherapy with gemcitabine and cisplatin followed by surgery (radical nephroureterectomy), while the other group will undergo surgery without chemotherapy. The primary goal is to assess the pathological response to treatment, focusing on how much the tumor shrinks before surgery. The trial will also evaluate the safety of the treatments, overall survival, and recurrence-free survival. This study will help determine whether adding chemotherapy before surgery improves outcomes for patients with high-risk UTUC.

Study Overview

• Status: Active, not recruiting
• Conditions: Neoadjuvant Therapy; Urothelial Carcinoma Ureter; Upper Urinary Tract Urothelial Carcinoma
• Intervention / Treatment: Drug: Neoadjuvant Gemcitabine + Cisplatin Chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200090
      • Changhai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed high-risk upper tract urothelial carcinoma (UTUC).
2. Clinically non-metastatic UTUC (N≤1, M0) based on imaging (CT/MRI).
3. Planned for radical nephroureterectomy (RNU).
4. ECOG performance status of 0 or 1.
5. Sufficient renal function (GFR ≥45 mL/min) and able to tolerate chemotherapy with cisplatin.
6. Age ≥18 years.
7. Informed consent signed.

Exclusion Criteria:

1. Imaging shows ≥N2 disease or metastatic disease (M1).
2. History of invasive or lymph node-positive UTUC or invasive disease in the contralateral upper tract in the last 2 years.
3. Single kidney or contraindication to cisplatin.
4. Currently participating in other interventional clinical trials.
5. History of non-urothelial malignancies (except treated skin basal cell carcinoma or cervical carcinoma in situ).
6. Pregnant or breastfeeding women.
7. Any other medical condition deemed inappropriate by the treating physician.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NAC+RNU	Drug: Neoadjuvant Gemcitabine + Cisplatin Chemotherapy; Patients in the experimental group will receive neoadjuvant chemotherapy with a combination of gemcitabine and cisplatin before undergoing surgery. The chemotherapy regimen consists of: Gemcitabine: 1000 mg/m², administered on Day 1 and Day 8 of each 21-day cycle. Cisplatin: 70 mg/m², administered on Day 2 of each 21-day cycle. This treatment will be repeated for 3 to 4 cycles. The goal of this chemotherapy is to shrink the tumor and improve the chances of a successful surgery. After completing the chemotherapy, patients will undergo radical nephroureterectomy (RNU), a surgery to remove the kidney and ureter affected by cancer, within 6 weeks (+/- 2 weeks) of the last chemotherapy cycle. This approach is designed to evaluate if chemotherapy before surgery can improve pathological response and long-term survival outcomes.
No Intervention: RNU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Response Rate	Proportion of patients with ypT1N0 or lower after surgery in the neoadjuvant chemotherapy + partial nephrectomy group compared to the direct partial nephrectomy group.	6 weeks after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chemotherapy Safety and Tolerability	Incidence, severity, and clinical management of treatment-related adverse events (TRAEs) according to CTCAE v5.0.	During chemotherapy and post-surgery follow-up
Overall Survival (OS)	Time from surgery to death from any cause.	24 months after surgery
Cancer-Specific Survival (CSS)	Time from surgery to death due to UTUC.	24 months after surgery
Recurrence-Free Survival (RFS)	Time from surgery to first recurrence of UTUC.	24 months after surgery

Collaborators and Investigators

• Sponsor: Changhai Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2025
• Primary Completion (Estimated): August 15, 2027
• Study Completion (Estimated): August 15, 2029

Study Registration Dates

• First Submitted: March 19, 2026
• First Submitted That Met QC Criteria: March 19, 2026
• First Posted (Actual): March 25, 2026

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: CH-UTUC NAC vs NNAC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data Privacy and Ethical Considerations: Due to the sensitive nature of the IPD, which contains private health information, sharing of this data may pose privacy risks and violate regulations such as GDPR or HIPAA. The study's ethical approval also restricts public access to IPD to safeguard patient confidentiality.; Data Security: To ensure the protection of patient information and prevent potential data breaches, access to the IPD will be strictly limited to the internal research team.; Lack of Data Sharing Agreement: While we support data sharing, a formal agreement with external researchers or public repositories has not been established for this study at present.; Group-level Analysis: The primary analyses of this study are based on aggregated group data rather than individual patient-level data. As such, sharing IPD does not significantly impact the reproducibility or verification of the study's results.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No