Circulating and Urine Tumor DNA Dynamics Predict Minimal Residual Disease and Guide Adjuvant Therapy in Locally Advanced Upper Tract Urothelial Carcinoma

Recruiting

• Conditions: Muscle Invasive Upper Tract Urothelial Carcinoma
• Interventions: Drug: Adjuvant chemotherapy; Drug: adjuvant immunotherapy

• Registration Number: NCT05595408
• Lead Sponsor: RenJi Hospital

Brief Summary

In our study, the ultra-deep sequencing of circulating tumor DNA (ctDNA) and urine tumor DNA (utDNA) were performed to assess whether ctDNA and utDNA can be used as predictive biomarkers for the detection of minimal residual disease (MRD) and early diagnosis of UTUC recurrence, and explored the role of ctDNA and utDNA detection of MRD in the prediction of adjuvant therapy efficacy and prognostic evaluation.

Detailed Description

60% of Upper Urinary Tract Urothelial Carcinoma (UTUC) patients with muscle-invasive disease at diagnosis, which progresses rapidly, aggressively, and has a poor prognosis. Up to 30-40% of the patients may develop bladder recurrance after radical nephroureterectomy for primary upper tract urothelial carcinoma.

Minimal residual disease (MRD) refers to the small number of malignant cells that remain after curative treatments (curative intent surgical resection, radiotherapy, and/or chemotherapy). MRD is common in patients with blood cancer, and is known to be associated with recurrence and poor prognosis. Recent studies also reported that MRD-negative in postoperative solid tumors such as colorectal/colon cancer and muscle-invasive bladder cancer is associated with better survival outcomes. However, the clinical values of MRD monitoring for adjuvant therapy in postoperative UTUC remain inadequate.

A total of 103 patients with stage II-IV UTUC will be recruited in this clinical trial. The following plasma samples, urine samples and tumor tissues will be collected from each patient including 1) preoperative plasma and urine samples; 2) surgical tissue samples; 3) plasma and urine samples 1 month after surgery; 4) plasma and urine samples during adjuvant therapy; and 5) plasma and urine samples after adjuvant therapy; 6) plasma and urine samples in follow-up. In addition, demographic and tumor characteristics of the patients will be collected for subsequent analysis, including age, sex, tumor stage, pathological stage, disease couse time, etc. Tumor tissues and matched peripheral blood were collected before treatment and WES was used ctDNA detection techniques. For each patient, we selected up to 30 clonal somatic mutations for personalized, tumor informed ctDNA assay design.Statistical analyses will be performed to analyze the survival outcomes and to explore the clinical value of MRD monitoring for adjuvant therapy in postoperative UTUC.

Study Timeline

• Study Start: 2022-02-01
• Study First Submitted: 2022-10-22
• Study First Submitted QC: 2022-10-22
• Study First Posted: 2022-10-27
• Primary Completion: 2024-12-31
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-20
• Last Update Posted: 2025-04-24
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 103

Inclusion Criteria

• pathological comfirmed T2-4 or N+ and M0 upper tract urothelial carcinoma
• Male or female aged ≥18 years old who are willing to sign the informed consent form
• have no distant metastasis
• have an ECOG 0 to 2
• upper tract urothelial carcinoma patients received radical nephroureterectomy
• have no multiple primary carcinoma
• received adjuvant chemotherapy or immunotherapy after surgery within 3 months

Exclusion Criteria

• a prior history of bladder or synchronous bladder cancer
• Pregnant or lactating women, or patients who are fertile but do not take contraceptive measures;
• Severe infection;
• Severe heart disease;
• Uncontrollable neurological or mental disorders;
• Severe diabetes mellitus;
• Patients with severe autoimmune diseases.
• No neoadjuvant therapy
• No bilateral UTUC
• Surveillance time ≤3 month
• <2 postoperative MRD surveillance assessments

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
adjuvant chemotherapy group	Adjuvant chemotherapy	muscle invasive upper tract urothelial carcinoma after radical nephroureterectomy receiving adjuvant chemotherapy
adjuvant immunotherapy group	adjuvant immunotherapy	muscle invasive upper tract urothelial carcinoma after radical nephroureterectomy receiving adjuvant immunotherapy

Primary Outcome Measures

Name	Time	Method
extravesical recurrence free survival	2 year

Secondary Outcome Measures

Name	Time	Method
The predictive value of ctDNA and utDNA	2 year
intravesical recurrence free survival	2 year

Trial Locations

Locations (1)

Renji Hospital; 🇨🇳 Shanghai, Shanghai, China