Multimodal Kidney-Sparing Strategy for High-Risk Upper Tract Urothelial Carcinoma

April 21, 2026 updated by: Xuesong Li, Peking University First Hospital

Evaluating a Kidney-sparing Strategy Combining Endoscopic Surgery, Adjuvant Radiotherapy, and HER2-targeted Antibody-Drug Conjugate in High-risk Upper Tract Urothelial Carcinoma: Study Protocol for a Prospective, Multicenter, Non-randomized Comparative Clinical Trial

UTUC is a cancer that develops in the lining of the kidney or ureter. The standard treatment is radical nephroureterectomy, which removes the kidney and ureter. Although this surgery can control the cancer, it permanently reduces kidney function.

Endoscopic treatment can serve as a kidney-sparing approach for low-risk UTUC; however, in high-risk patients, the high rate of upper tract local recurrence after endoscopic treatment remains the primary failure pattern. This study aims to evaluate the efficacy and safety of radiotherapy-involved kidney-sparing treatment for UTUC.

The main questions this study aims to answer are: Can this multimodal kidney-sparing strategy reduce local recurrence of UTUC compared with endoscopic treatment alone? Participants in the kidney-sparing group will: Undergo endoscopic surgery to remove the tumor; Receive systemic therapy with disitamab vedotin and toripalimab; Receive targeted radiotherapy after surgery.

Participants will undergo regular follow-up visits, including imaging examinations and endoscopic evaluations, to monitor for recurrence or disease progression.

The results of this study may help determine whether a multimodal kidney-sparing treatment strategy could become a safe and effective option for selected patients with high-risk UTUC.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Upper tract urothelial carcinoma (UTUC) is an uncommon malignancy arising from the urothelial lining of the renal pelvis or ureter. Radical nephroureterectomy (RNU) remains the standard treatment for high-risk disease. However, removal of the entire kidney and ureter leads to permanent loss of renal function and may negatively affect long-term quality of life and eligibility for future systemic therapies. Although kidney-sparing treatment is well established for low-risk UTUC, its role in patients with high-risk disease remains uncertain.

Recent advances in systemic therapy and radiotherapy have created opportunities to explore multimodal treatment strategies aimed at improving oncological control while preserving renal function. HER2 expression appears to be relatively frequent in UTUC, and HER2-targeted antibody-drug conjugates such as disitamab vedotin have demonstrated promising activity in urothelial carcinoma. In addition, immune checkpoint inhibitors have improved outcomes in advanced urothelial malignancies. Radiotherapy has also been reported to improve locoregional tumor control in selected patients. These developments provide the rationale for integrating endoscopic tumor management with systemic therapy and selective radiotherapy as part of a comprehensive kidney-sparing strategy.

This prospective multicenter study is designed to evaluate the feasibility, safety, and preliminary oncological outcomes of a multimodal kidney-sparing treatment pathway in patients with high-risk UTUC.

The findings of this study are expected to provide prospective evidence regarding the feasibility of a multimodal kidney-sparing strategy for selected patients with high-risk UTUC and may inform the design of future confirmatory clinical trials.

Sample size considerations Given the low incidence of UTUC and the fact that kidney-sparing treatment has not yet been established as a standard-of-care for high-risk disease, the sample size calculation was primarily based on a benchmark comparison against previously published outcomes from kidney-sparing treatment cohorts. According to available literature, the reported 1-year DFS rate following endoscopic tumor ablation combined with systemic therapy was approximately 58.82% [Chen Z, Ye J, Tu X, et al. Comprehensive modalities of kidney-sparing treatment in a carefully selected cohort of localized high-risk upper tract urothelial carcinoma: a potential paradigm shift. J Clin Oncol. 2025;43(5_suppl):794-794. doi:10.1200/JCO.2025.43.5_suppl.794]. In this study, we hypothesized that the incorporation of radiotherapy into a comprehensive kidney-sparing strategy would increase the 1-year DFS to 85%. Assuming a two-sided significance level of 0.05 and a statistical power of 80%, and accounting for a 20% dropout rate due to potential loss to follow-up and pathological heterogeneity at enrollment, the required sample size was estimated at 36 patients in the kidney-sparing group.

Study Type

Observational

Enrollment (Estimated)

36

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
      • Beijing, China
        • Departmeng of Urology, Peking University First Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with clinically histologically confirmed high-risk upper tract urothelial carcinoma who are evaluated and treated at Peking University First Hospital and participating centers will be screened for eligibility. Participants who meet the inclusion criteria and provide informed consent will be enrolled in the kidney-sparing treatment cohort or the radical nephroureterectomy cohort according to clinical decision-making and treatment preference.

Description

Inclusion Criteria

Participants must meet all of the following criteria:

Age 18 years or older Voluntary participation with written informed consent Pathology indicating upper tract urothelial carcinoma with HER2 at least 1+ expression Clinical stage cT1-T2N0M0 based on imaging evaluation Classified as high-risk upper tract urothelial carcinoma according to European Association of Urology (EAU) criteria Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Adequate renal function with split renal function of the affected kidney ≥10 mL/min on renal dynamic scintigraphy Expected life expectancy greater than 24 months Ability and willingness to comply with study procedures and follow-up schedule Exclusion Criteria

Participants will be excluded if any of the following conditions are present:

Inability to tolerate or refusal of kidney-sparing treatment Evidence of advanced disease (≥T3), lymph node metastasis, or distant metastasis Synchronous bladder urothelial carcinoma or other urological malignancies Previous systemic anticancer therapy, including chemotherapy, targeted therapy, immunotherapy, or antibody-drug conjugates Prior radiotherapy involving the urinary tract or retroperitoneal region Severe uncontrolled comorbidities such as cardiovascular, pulmonary, neurological, psychiatric, or systemic diseases Active severe infections requiring systemic antimicrobial therapy Known immune-related disorders requiring long-term immunosuppressive treatment Pregnancy or breastfeeding Known allergy to investigational drugs used in this study Concurrent participation in another therapeutic clinical trial Indeterminate postoperative pathological diagnosis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Kidney-Sparing Multimodal Treatment
Participants undergo endoscopic tumor ablation or resection using thulium fiber laser techniques. Participants without confirmed complete tumor resection will receive selective hypofractionated radiotherapy approximately one month after surgery.Postoperative systemic therapy consists of disitamab vedotin administered every three weeks for eight cycles combined with toripalimab administered every three weeks for up to one year.
Radiation: SBRT
Participants without confirmed complete tumor resection will receive selective hypofractionated radiotherapy approximately one month after surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
One-Year Disease-Free Survival
Time Frame: 12 months after surgery
Disease-free survival is defined as the proportion of participants who remain alive without evidence of local recurrence, upper urinary tract recurrence, intravesical recurrence, disease progression, or distant metastasis.
12 months after surgery
One-Year kidney-sparing rate
Time Frame: 12 months after surgery
One-Year kidney-sparing rate is defined as the proportion of participants who do not require conversion to radical nephroureterectomy due to disease progression after initial kidney-sparing treatment.
12 months after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: Up to 5 years
Overall survival is defined as the time from surgery to death from any cause.
Up to 5 years
Progression-Free Survival
Time Frame: Up to 5 years
Progression-free survival is defined as the time from surgery to disease progression or death from any cause.
Up to 5 years
Local Recurrence-Free Survival
Time Frame: Up to 5 years
Time from surgery to detection of tumor recurrence at the primary surgical site confirmed by ureteroscopic evaluation.
Up to 5 years
Intravesical Recurrence-Free Survival
Time Frame: Up to 5 years
Time from surgery to first documented bladder tumor recurrence confirmed by cystoscopic examination.
Up to 5 years
Metastasis-Free Survival
Time Frame: Up to 5 years
Time from surgery to development of distant metastatic disease confirmed by imaging.
Up to 5 years
Treatment-Related Adverse Events
Time Frame: From treatment initiation to 12 months
Adverse events will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE).
From treatment initiation to 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University First Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2026

Primary Completion (Estimated)

April 1, 2030

Study Completion (Estimated)

April 1, 2030

Study Registration Dates

First Submitted

March 8, 2026

First Submitted That Met QC Criteria

March 26, 2026

First Posted (Actual)

April 1, 2026

Study Record Updates

Last Update Posted (Actual)

April 24, 2026

Last Update Submitted That Met QC Criteria

April 21, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • LUXUS3.1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

The plan for sharing individual participant data (IPD) has not yet been determined. Data sharing may be considered after completion of the study and publication of the primary results, subject to institutional policies, ethical approvals, and data protection regulations.

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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