Clinical trial NCT06153849: Analyzing the Urine During BCG Instillation in Bladder Cancer Patients for Disease Followup
Official title: Analyzing the Urine Microbiome and Chromosomal Instability by Whole Genome Sequening in Bladder Cancer Patients During BCG Instillation for Disease Follow-up
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Bladder Cancer
Keywords: Bladder cancer
Urine biomarker
Microbiome
Bacillus Calmette-Guérin instillation
Chromosomal instability
Low coverage whole genome sequencing
Lead sponsor: Changhai Hospital
Sponsor class: OTHER
First posted: 2023-12-01
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with medianl to high risk NMIBC underwent TURBT and received BCG instillation therapy in Changhai Hospital

Brief summary: Bacillus Calmette-Guerin (BCG) has been extensively utilized in intravesical instillation therapy for patients with medium to high risk non-muscle invasive bladder cancer (NMIBC) following transurethral resection of bladder tumor (TURBT). Nevertheless, the efficacy of BCG instillation can fluctuate between patients, with 40.5% experiencing disease recurrence during BCG therapy. The effectiveness of BCG instillation may be linked to the urinary microbiome and immune microenvironment. Additionally, small residual lesions post-TURBT could also result in bladder cancer recurrence. Low coverage whole genome sequencing (LC-WGS) can be used to detect the urinary microbiome and chromosomal instability (CIN), making it feasible to predict the recurrence or progression of bladder cancer during BCG instillation therapy. Here, we intend to evaluate the feasibility of detecting urine samples of bladder cancer patients receiving BCG instillation to predict the bladder cancer recurrence.

Detailed description: NMIBC at medium to high risk showcases a recurrence rate of 40.5% post-TURBT, thus necessitating frequent monitoring and bladder instillation. Among patients with medium to high-risk NMIBC, the preferred treatment is BCG. The high recurrence rate of this illness is associated with BCG's effectiveness and residual cancer, yet the full understanding of BCG installation's mechanism complicates the prediction of its efficacy among individuals with bladder cancer.

Previously, it was believed that the urinary system was sterile; however, recent high-throughput sequencing and enhanced quantitative urine culture have confirmed the presence of resident bacteria in the urine of healthy individuals. Microorganisms within the bladder have the potential to alter the immune microenvironment, consequently impacting the efficacy of BCG instillation.

CIN denotes continuous errors in chromosome separation during cell division, encompassing numerical and structural instability. Loss of the Y chromosome (LOY) represents a specific type of CIN associated with cancer prognosis. CIN serves as a hallmark of malignancies and can be employed to indicate the presence of minimal residual disease (MRD) subsequent to TURBT. Analyzing LOY can better elucidate the disease's progression, and more exploration is necessary to comprehend the significance of detecting CIN for predicting tumor recurrence.

LC-WGS is a cost-effective, efficient, and robust technique that can be used to analyze both microorganism and human genomes in urine samples. The microbiome is commonly detected using 16S ribosomal sequencing. Compared to 16S sequencing, LC-WGS provides advantages such as enhanced detection of bacterial species, diversity, and improved gene prediction. In the context of CIN and LOY detection, LC-WGS technology offers heightened sensitivity, low cost, and high throughput compared to traditional methods such as comparative genomic hybridization or fluorescence in situ hybridization.

In this prospective, single-arm observational clinical trial, the investigators aim to evaluate LOY, CIN, and the urinary microbiome detected by LC-WGS for the assessment of BCG instillation efficacy and NMIBC follow-up.

Eligibility criteria: Inclusion Criteria:

* Participants aged ≥ 18 years and signed informed consent form.
* Participants diagnosed with median to high risk NMIBC underwent TURBT and received BCG instillation therapy.

Exclusion Criteria:

* Participants with urinary tract infection
* Antibiotic treatment within the last month
* Immuno- /chemo- therapy within the past 6 months
* Immunosuppressive therapy
* Indwelling urinary catheter
* Additional major diagnosis known to affect the gut or bladder microbiota (e. g. liver cirrhosis, systemic sclerosis, inflammatory bowel disease, inflammatory bowel syndrome, celiac disease, neuropathic bladder)
* Participants with urothelial carcinoma accompanied by other malignancy.
* Individuals unwilling to sign the consent form or unwilling to provide urine sample for test or quality of urine sample is poor.

Primary outcomes:
measure: Correlation between urinary microbiome and BCG instillation efficacy.
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: Correlation between LOY and prognosis.
timeFrame: through study completion, an average of 1 year
measure: Correlation between CIN and tumor relapse
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Changhai Hospital
state: Shanghai
Study officials:
References:
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