Multiplex Mutation Detection Using Mass Spectrometry in Bladder Cancer

NCT07424560 | Recruiting DMC

• 1 other identifier: LZU2H-BC-MASS-2026
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

Bladder cancer is a highly heterogeneous malignancy characterized by frequent genetic alterations that are closely associated with disease progression, recurrence risk, and treatment response. However, existing mutation detection approaches are often limited by high cost, complex workflows, or insufficient capacity for multiplex and low-frequency mutation analysis, which restricts their routine clinical application. The purpose of this study is to establish and clinically validate a multiplex mutation detection system for bladder cancer based on nucleic acid mass spectrometry. Using fresh tumor tissue and matched adjacent normal tissue samples collected from patients with bladder cancer, a targeted mutation panel comprising key functional mutations with demonstrated clinical relevance will be constructed. The matched normal tissues serve as germline references to enable accurate identification of somatic mutations. The analytical performance of the system, including sensitivity, specificity, and concordance with whole-genome sequencing, will be systematically evaluated. In addition, the clinical utility of the mutation panel in risk stratification and treatment decision support will be explored by comparing its predictive value with established clinical models and guideline-recommended tools. The ultimate goal is to develop a cost-effective, reproducible, and clinically applicable molecular testing strategy that can support precision diagnosis and individualized management of patients with bladder cancer.

Conditions

Bladder Cancer; Bladder Cancer Recurrence; Adjuvant Therapy for Bladder Cancer; Progression of Bladder Cancer

Keywords

Nucleic acid mass spectrometry; Bladder cancer; Gene mutations; High-throughput detection; Risk stratification; Adjuvant therapy sensitivity

Outcome Measures

Primary Outcomes (1)

• Survival Differences Between Mutated and Non-mutated Groups in Bladder Cancer Patients

  This outcome measure aims to compare the survival rates between bladder cancer patients with mutations in key bladder cancer-related genes (as determined by the multiplex mutation detection panel) and those without mutations. The mutation status (any gene mutation versus no mutation) will be correlated with clinical outcomes, including recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS), using Kaplan-Meier survival analysis. These survival metrics will be assessed to determine whether mutation status influences prognosis and to identify any significant survival differences between mutated and non-mutated groups.

  Survival will be assessed at post-surgical follow-up at 6 months, 1 year, 2 years, and 3 years, including recurrence, progression, and metastasis-free survival events over a 3-year period.

Secondary Outcomes (2)

• Development of Predictive Models for Post-surgical Recurrence, Progression, and Response to Intravesical Therapy

  The predictive model will be developed and evaluated during the 3-year follow-up period post-surgery, with data collected at key intervals: 6 months, 1 year, 2 year, and 3 years post-surgery.

• Validation of Mutation Panel's Predictive Value in Risk Stratification Using Existing Clinical Models

  Validation will occur after 3 years of patient follow-up, at the point of comparing the prediction models for their efficacy in risk stratification and recurrence prediction.

Study Arms (2)

NMIBC (Non-Muscle Invasive Bladder Cancer) Study Group

This cohort includes patients diagnosed with non-muscle invasive bladder cancer. Participants are categorized according to post-operative recurrence and progression status, as well as response to intravesical therapy (recurrence versus no recurrence; response versus non-response). Survival differences between mutation-positive and mutation-negative groups will be assessed using Kaplan-Meier survival analysis. Predictive models for post-surgical recurrence, progression, and treatment response will be developed using multivariable Cox proportional hazards regression analysis. Model performance will be validated in 30% of participants and compared with established risk models from the European Association of Urology and the European Organisation for Research and Treatment of Cancer.

Genetic: Multiplex Mutation Detection System for Bladder Cancer (Nucleic Acid Mass Spectrometry)

MIBC (Muscle Invasive Bladder Cancer) Study Group

This cohort includes patients diagnosed with muscle invasive bladder cancer. Participants are categorized according to recurrence after adjuvant therapy and the presence or absence of distant metastasis. Survival differences between mutation-positive and mutation-negative groups will be assessed using Kaplan-Meier survival analysis. A predictive model for recurrence and distant metastasis following adjuvant therapy will be developed using multivariable Cox proportional hazards regression analysis. Model performance will be validated in the remaining 30% of participants. Predictive accuracy will be compared with existing clinical assessment methods, including clinicopathological characteristics, single-gene mutation markers, and immunohistochemical biomarkers.

Genetic: Multiplex Mutation Detection System for Bladder Cancer (Nucleic Acid Mass Spectrometry)

Interventions

Multiplex Mutation Detection System for Bladder Cancer (Nucleic Acid Mass Spectrometry) GENETIC

This study uses a multiplex mutation detection system for bladder cancer based on nucleic acid mass spectrometry. The system is designed to identify genetic alterations in bladder cancer-related genes, including Fibroblast Growth Factor Receptor 3 (FGFR3), Tumor Protein P53 (TP53), and other relevant genes. The platform offers high-throughput, multiplex mutation detection with high analytical sensitivity and cost efficiency, suitable for potential clinical use. Tumor tissue samples will be prospectively collected from patients with bladder cancer who elect to undergo surgery. The study is observational, with no active intervention, therapeutic modification, or influence on clinical treatment decisions. Mutation status from tissue analysis will be evaluated for correlations with clinical outcomes, including recurrence, progression, and treatment response.

MIBC (Muscle Invasive Bladder Cancer) Study Group; NMIBC (Non-Muscle Invasive Bladder Cancer) Study Group

Eligibility Criteria

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

Study Population

This study will include adult patients aged 18 years or older with a histologically confirmed diagnosis of urothelial carcinoma of the bladder, including both non-muscle invasive bladder cancer and muscle invasive bladder cancer. Eligible participants must have sufficient fresh frozen tumor tissue samples available for DNA extraction and mutation analysis. Exclusion criteria include inadequate tumor tissue DNA quality for mutation analysis, pregnancy or breastfeeding, and serious uncontrolled intercurrent illnesses that may interfere with study participation. The study population will be representative of bladder cancer patients receiving standard clinical management, focusing on genetic mutation profiling for improved risk stratification and treatment prediction.

You may qualify if:

• Histologically confirmed diagnosis of urothelial carcinoma of the bladder (any stage, including non-muscle invasive and muscle invasive).
• Availability of sufficient tumor tissue specimen (fresh frozen) for DNA extraction and mutation analysis.
• Age ≥ 18 years at time of diagnosis.

You may not qualify if:

• History of other malignant tumors within the past 5 years, except adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix.
• Inadequate quality or quantity of tumor tissue DNA for mutation panel analysis (e.g., severe DNA degradation, insufficient DNA yield).
• Pregnancy or breastfeeding.
• Serious uncontrolled intercurrent illness that would interfere with study follow-up or compliance, including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• Zhilong Dong: lead

Study Sites (1)

The Second Hospital of Lanzhou University

Lanzhou, Gansu, 730030, China

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Tumor tissue (fresh frozen) and matched adjacent normal tissue (fresh frozen) will be retained. Each tissue sample will be divided into four aliquots at the time of collection: two aliquots will be immediately stored at -80°C for subsequent DNA extraction, and the remaining two aliquots will be immersed in RNA preservation solution, incubated at 4°C overnight, and then transferred to -80°C for subsequent RNA extraction. The residual DNA and RNA after extraction will also be archived for potential future studies.

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Zhilong Dong, Doctor of Medicine

  Lanzhou University Second Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Weiguang Yang, Doctor of Medicine

CONTACT

+86 18221095087; yangwg2024@lzu.edu.cn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Urology

Study Record Dates

• First Submitted: February 14, 2026
• First Posted: February 20, 2026
• Study Start: February 25, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: February 24, 2026

Record last verified: 2026-02

Locations

CN (1)