Can We Predict of the Response of High Risk Non Muscle Invasive Bladder Cancer Patients to Intravesical Bacillus Calmette-Guerin? The Role of Immunological Markers

Study Overview
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Brief Summary
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Intravesical BCG is the mainstay adjuvant management of high risk NMIBC. Adequacy of immune system stimulation is the determinant factor for patient response to BCG. Immunological markers for BCG-response could be helpful for urologists especially in the era of BCG shortage. Objectives: To assess the predictive performance of different immunological markers on BCG-response in high risk NMIBC BCG-naïve patients.

Detailed Description
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Background: Intravesical BCG is the mainstay adjuvant management of high risk NMIBC. Adequacy of immune system stimulation is the determinant factor for patient response to BCG. Immunological markers for BCG-response could be helpful for urologists especially in the era of BCG shortage. Objectives: To assess the predictive performance of different immunological markers on BCG-response in high risk NMIBC BCG-naïve patients.

Official Title
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Can We Predict of the Response of High Risk Non Muscle Invasive Bladder Cancer Patients to Intravesical Bacillus Calmette-Guerin? The Role of Immunological Markers

Conditions
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Bladder Cancer

Intervention / Treatment
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* Diagnostic Test: Urine ELISA for immunological markers (IL-2 and IL-10)
* Diagnostic Test: Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with primary or recurrent NMIBC for whom primary TURBT was done. Exclusion Criteria: Patients with previous BCG instillation, benign pathology Variant histology Non urothelial carcinoma, concommitent upper tract urothelial tumors, detrusor muscle invasion low or intermediate risk NMIBC

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: High risk NMIBC<br>Patients with primary or recurrent NMIBC for whom primary TURBT was done and intravesical BCG was administered | Diagnostic Test: Urine ELISA for immunological markers (IL-2 and IL-10)<br>* IL-2 and IL-10 levels were measured in the supernatants. Natural human-produced IL-2 and IL-10 concen¬trations were determined in the urine of all patients and controls by solid phase ELISA Quantikine IL-2 Immunoassay and IL-10 Immunoassay, respectively<br>Diagnostic Test: Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) analysis<br>* blood samples using QIAamp® RNA Blood Mini kit (QIAGEN, USA). 1 μg of total RNA was reverse transcribed with random primers, using High Capacity cDNA Archive Kit (Applied Biosystems, Foster City, CA, USA). RT-qPCR analysis was carried out with SYBER Green PCR Master Mix (Applied Biosystems, Foster City, CA, USA). Primers for TNF-α, CTLA4, T-bet+, GATA3+, FoxP3+ and GABDH as PCR control<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Initial BCG complete response | free cystoscopy/negative cytology at 3 months. | 3 months | 
| Recurrence | Recurrence is defined as development of new tumor/positive cytology in patients with ICR | 1 year | 
| Progression | persistent/recurrent tumor during or after treatment with increasing tumor grade or upstaging to muscle invasion after initial complete response | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bladder cancer, Bacillus Calmette-Guérin response, Prediction, Urinary cytokines, T cells, Recurrence, Progression