Circulating and Urine Tumor DNA Dynamics Predict Minimal Residual Disease and Recurrence Risk in Locally Advanced Upper Tract Urothelial Carcinoma

Circulating and Urine Tumor DNA Dynamics Predict Minimal Residual Disease and Recurrence Risk in Locally Advanced Upper Tract Urothelial Carcinoma(CURATE-UTUC): A Multicenter Prospective Longitudinal Cohort Study

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.

Study Overview

• Status: Recruiting
• Conditions: Muscle Invasive Upper Tract Urothelial Carcinoma
• Intervention / Treatment: Drug: Adjuvant chemotherapy; Drug: adjuvant immunotherapy

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 84 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 T0 (preoperatively, 2[1-3] days before surgery), T1 (28±3 days postoperatively), T2 (within 7 days after cycle 2 adjuvant therapy), T3 (end-of-treatment), and quarterly/semi-annually during surveillance (T4-T6) until recurrence/24 months. 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 40 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 Type: Observational
• Enrollment (Estimated): 84

Contacts and Locations

• Study Contact: Name: jiwei huang, M.D; Phone Number: 8613651682825; Email: huangjiwei@renji.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200127
      • Recruiting
      • Renji Hospital
      • Contact: jiwei huang, M.D; Phone Number: 8621-68383716; Email: huangjiwei@renji.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

pathological comfirmed T2-4 or N+ and M0 upper tract urothelial carcinoma patients who received adjuvant chemotherapy or immunotherapy after radical nephroureterectomy

Description

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 12 weeks
• ≥2 postoperative liquid biopsy assessments (T1 and T2)

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.
• Neoadjuvant therapy exposure
• No bilateral UTUC
• Surveillance time < month
• <2 postoperative MRD surveillance assessments

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
adjuvant chemotherapy group; muscle invasive upper tract urothelial carcinoma after radical nephroureterectomy receiving adjuvant chemotherapy	Drug: Adjuvant chemotherapy; cisplatin/carboplatin-gemcitabine 4-6 cycles
adjuvant immunotherapy group; muscle invasive upper tract urothelial carcinoma after radical nephroureterectomy receiving adjuvant immunotherapy	Drug: adjuvant immunotherapy; immunotherapy for one year

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
extravesical recurrence free survival	The primary endpoint was extravesical recurrence-free survival (eRFS), defined as the time from radical nephroureterectomy (RNU) to the first occurrence of either locoregional recurrence (e.g., retroperitoneal lymph node, local soft tissue) or distant metastasis, as objectively confirmed by radiological imaging (CT or MRI) according to RECIST 1.1 criteria. Death from any cause without a prior documented extravesical recurrence was considered a competing risk event.	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lead time of molecular recurrence detection	the interval from the first postoperative MRD-positive liquid biopsy to radiologic/cyotscopic	2 year
intravesical recurrence free survival	bladder or contralateral upper tract relapse confirmed by cystoscopy/ureteroscopy and biopsy	2 year
recurrence-free survival	Defined as the time from RNU to the first occurrence of any recurrence (including both extravesical and intravesical events).	2 year
Overall survival	efined as the time from RNU to death from any cause	2 year
Diagnostic performance of MRD assay	The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ctDNA (at T1, T2) for predicting extravesical recurrence, and of utDNA (at T2) for predicting intravesical recurrence, against the imaging and cystoscopic gold standards.	2 year

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Collaborators: West China Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Actual): November 3, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: October 22, 2022
• First Submitted That Met QC Criteria: October 22, 2022
• First Posted (Actual): October 27, 2022

Study Record Updates

• Last Update Posted (Estimated): December 9, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: adjuvant chemotherapy; Circulating tumor DNA; Minimal residual disease; upper tract urothelial carcinoma; Urine tumor DNA; adjuvant immunotherapy
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm, Residual; Therapeutics; Drug Therapy; Combined Modality Therapy; Chemotherapy, Adjuvant
• Other Study ID Numbers: CURATE-UTUC

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