Validation of a Circulating Tumor DNA Blood Test in Muscle-Invasive Bladder and Upper Tract Urothelial Cancer

NCT07756437 | Recruiting

• 1 other identifier: 2025-18
• Study Type: observational
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective observational study evaluates a blood-based circulating tumor DNA (ctDNA) test in patients with muscle-invasive bladder cancer or upper tract urothelial cancer. ctDNA consists of small fragments of tumor DNA that can sometimes be detected in the blood. In this study, DNA from tumor tissue obtained during routine diagnostic or surgical procedures will be analyzed to identify tumor-specific mutations. Blood samples collected during routine clinical care will then be tested to determine whether the same mutations can be detected in plasma ctDNA. The main purpose is to assess how well the internally developed ctDNA assay detects tumor-specific mutations compared with tumor tissue sequencing. The study will also explore whether ctDNA results after treatment are associated with recurrence or remission during two years of follow-up, and whether changes in ctDNA levels during treatment are associated with pathological response. This study does not assign participants to a treatment and does not require additional blood draws beyond routine care. Treating physicians will remain blinded to ctDNA results during the study, so the test results will not influence clinical decisions.

Conditions

Upper Tract Urothelial Carcinoma; Urothelial Carcinoma (UC); Muscle-Invasive Bladder Cancer (MIBC)

Keywords

Circulating Tumor DNA; ctDNA; Liquid biopsy; Tumor-Informed Sequencing; Minimal Residual Disease; MRD; Muscle-Invasive Bladder Cancer; Upper Tract Urothelial Carcinoma; Urothelial carcinoma; Next-Generation Sequencing; NGS; Recurrence Monitoring; Treatment response

Outcome Measures

Primary Outcomes (1)

• Diagnostic Performance of Plasma ctDNA for Detecting Tumor-Specific Mutations

  Concordance between tumor-specific somatic mutations identified in tumor tissue and the same mutations detected in matched plasma-derived ctDNA. Diagnostic performance of the internally developed ctDNA assay will be assessed using sensitivity, specificity, positive predictive value, and negative predictive value, with tumor tissue sequencing as the reference standard.

  From enrollment until completion of tumor tissue sequencing and matched plasma ctDNA analysis, up to 6 months

Secondary Outcomes (5)

• Association Between Post-Treatment ctDNA Positivity and Disease Recurrence or Progression

  Up to 2 years after surgery or radiotherapy

• Association Between Post-Treatment ctDNA Negativity and Disease Remission

  Up to 2 years after surgery or radiotherapy

• Association Between Preoperative ctDNA Negativity and Pathological T0 Status

  At cystectomy

• Association Between Quantitative ctDNA Decrease During Neoadjuvant Therapy and Pathological Downstaging

  From start of neoadjuvant therapy until cystectomy, up to 6 months

• Time Difference Between ctDNA Rise and Imaging-Detected Disease Relapse

  Up to 2 years after curative treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients with muscle-invasive bladder cancer or suspected muscle-invasive upper tract urothelial carcinoma treated at AZ Sint-Lucas Gent. Participants must have available tumor tissue for DNA extraction and matched plasma samples obtained during routine clinical care.

You may qualify if:

• Age 18 years or older.
• Histologically confirmed muscle-invasive bladder cancer or suspected muscle-invasive upper tract urothelial carcinoma, stage T2 or higher.
• Availability of tumor tissue from transurethral resection of bladder tumor, ureteroscopic biopsy, biopsy of a metastatic lesion, or nephroureterectomy for DNA extraction.
• Written informed consent provided.

You may not qualify if:

• \- Concurrent active malignancy diagnosed within the past 5 years.

Sponsors & Collaborators

• AZ Sint-Lucas Gent: lead

Study Sites (1)

AZ Sint-Lucas Gent

Ghent, East Flanders, 9000, Belgium

RECRUITING

Related Publications (5)

• Carrasco R, Ingelmo-Torres M, Gomez A, Trullas R, Roldan FL, Ajami T, Moreno D, Rodriguez-Carunchio L, Alcaraz A, Izquierdo L, Mengual L. Cell-Free DNA as a Prognostic Biomarker for Monitoring Muscle-Invasive Bladder Cancer. Int J Mol Sci. 2022 Oct 3;23(19):11732. doi: 10.3390/ijms231911732.

  PMID: 36233035 BACKGROUND

• Lindskrog SV, Birkenkamp-Demtroder K, Nordentoft I, Laliotis G, Lamy P, Christensen E, Renner D, Andreasen TG, Lange N, Sharma S, ElNaggar AC, Liu MC, Sethi H, Aleshin A, Agerbaek M, Jensen JB, Dyrskjot L. Circulating Tumor DNA Analysis in Advanced Urothelial Carcinoma: Insights from Biological Analysis and Extended Clinical Follow-up. Clin Cancer Res. 2023 Dec 1;29(23):4797-4807. doi: 10.1158/1078-0432.CCR-23-1860.

  PMID: 37782315 BACKGROUND

• Nordentoft I, Lindskrog SV, Birkenkamp-Demtroder K, Gonzalez S, Kuzman M, Levatic J, Glavas D, Ptashkin R, Smadbeck J, Afterman D, Lauterman T, Cohen Y, Donenhirsh Z, Tavassoly I, Alon U, Frydendahl A, Rasmussen MH, Andersen CL, Lamy P, Knudsen M, Polak P, Zviran A, Oklander B, Agerbaek M, Jensen JB, Dyrskjot L. Whole-genome Mutational Analysis for Tumor-informed Detection of Circulating Tumor DNA in Patients with Urothelial Carcinoma. Eur Urol. 2024 Oct;86(4):301-311. doi: 10.1016/j.eururo.2024.05.014. Epub 2024 May 29.

  PMID: 38811314 BACKGROUND

• Powles T, Assaf ZJ, Degaonkar V, Grivas P, Hussain M, Oudard S, Gschwend JE, Albers P, Castellano D, Nishiyama H, Daneshmand S, Sharma S, Sethi H, Aleshin A, Shi Y, Davarpanah N, Carter C, Bellmunt J, Mariathasan S. Updated Overall Survival by Circulating Tumor DNA Status from the Phase 3 IMvigor010 Trial: Adjuvant Atezolizumab Versus Observation in Muscle-invasive Urothelial Carcinoma. Eur Urol. 2024 Feb;85(2):114-122. doi: 10.1016/j.eururo.2023.06.007. Epub 2023 Jul 26.

  PMID: 37500339 BACKGROUND

• Crupi E, de Padua TC, Marandino L, Raggi D, Dyrskjot L, Spiess PE, Sonpavde GP, Kamat AM, Necchi A. Circulating tumor DNA as a Predictive and Prognostic Biomarker in the Perioperative Treatment of Muscle-invasive Bladder Cancer: A Systematic Review. Eur Urol Oncol. 2024 Feb;7(1):44-52. doi: 10.1016/j.euo.2023.05.012. Epub 2023 Jun 15.

  PMID: 37330413 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

plasma/cfDNA and tumor DNA are extracted/stored/analyzed.

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Neoplasm, Residual

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Jeroen Van Besien, MD

CONTACT

003292246650; Secretariaat.Urologie@AZSTLUCAS.BE

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2026
• First Posted: August 10, 2026
• Study Start: November 7, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): June 1, 2029
• Last Updated: August 10, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)