Multi-parameter Magnetic Resonance Imaging Guides Precise Treatment of Urothelial Carcinoma

Study Overview
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Brief Summary
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Purpose：To evaluate whether immediate multiparametric MRI evaluate the sensitivity of modified neoadjuvant chemotherapy early in patient with muscle invasive bladder cancer（MIBC）. Rationale：Multiparametric MRI may help detect the early changes of bladder cancer receiving neoadjuvant chemotherapy.

Detailed Description
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Objective Primary: To evaluate whether multiparametric MRI can determine the sensitivity of modified neoadjuvant chemotherapy early in patient with muscle invasive bladder cancer（MIBC）. Secondary：To determine whether multiparametric MRI can predict the prognosis of modified neoadjuvant chemotherapy early in patient with muscle invasive bladder cancer. Patients may receive neoadjuvant chemotherapy (typically three 21-day courses of modified gemcitabine-cisplatin(GC) therapy) followed by radical cystectomy and lymph node dissection. Patients with primary bladder cancer or recurrence which is confirmed by pathology of previous biopsy or TURBT, undergo a multiparametric MRI(mpMRI) at baseline to stage the primary tumor. The mpMRI includes T2-weighted MRI, diffusion-weighted imaging, and dynamic contrast enhancement, which will be given a five-point VI-RADS（Vesical Imaging-Reporting And Data System） score by two radiologists specialized in urogenital radiology. Patients considered NMIBC（Non-muscle invasive bladder cancer） with mpMRI will be given TURBT, while patients with MIBC（Muscle invasive bladder cancer）will receive radical cystectomy and lymph node dissection after three 21-day courses of modified gemcitabine-cisplatin neoadjuvant chemotherapy. Patients also undergo an immediate mpMRI scan after one, two, and three cycles of neoadjuvant chemotherapy. Specimens from the radical cystectomy are then examined by the pathology department as standard routine.

Official Title
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Multi-parameter Magnetic Resonance Imaging for Early Evaluation of the Efficacy of Neoadjuvant Chemotherapy With Modified GC Regimen for Urothelial Carcinoma

Conditions
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Bladder Cancer

Intervention / Treatment
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* Drug: Chemotherapy
* Diagnostic Test: Immediate Multiparametric MRI
* Procedure: Cystectomy and Lymphadenectomy
* Diagnostic Test: conventional Multiparametric MRI
* Diagnostic Test: Baseline Multiparametric MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed primary or recurrent bladder cancer. Planned to undergo transurethral resection of bladder tumor (TURBT) or modified GC regimen neoadjuvant chemotherapy plus radical total cystectomy. 18 years old and older. Willing to give valid written informed consent. No contraindications to the MRI(magnetic resonance imaging) and MRI contrast agent. Exclusion Criteria: Abnormal liver function (1.5 times higher than normal). Glomerular filtration rate < 60ml /min·kg. Heart failure. Acute myocardial infarction. Severe heart and lung disease. Hypotension and hypoxia. Brain metastases, or other known central nervous system metastases. A history of severe central nervous system diseases, including unexplained loss of consciousness or transient ischemic attack. Known congenital or acquired immunodeficiency, active hepatitis, active tuberculosis and other active infections, etc. Pregnant or lactating women. Patients participating in other drug trials. Patients with poor general condition (eg malnutrition, dehydration). Behavioral status score (ZPS quintile) ≥ 2. Patients with previous autoimmune diseases or existing autoimmune diseases. (including controlled or uncontrolled drugs). Patients undergoing organ transplantation (transplantation of liver, kidney, heart, lung and other organs) or those who require long-term administration of immunosuppressive agents due to personal conditions. Those who are intolerant or allergic to cytotoxic chemotherapeutic drugs. Bone marrow transplantation, severe leukopenia. Patients with severe infection or trauma. Any condition based on the investigation's clinical judgment that the patient is not suitable for completing this study (such as not meeting the patient's most beneficial treatment, patient compliance, etc.)

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Chemotherapy + mpMRI + surgery<br>Baseline mpMRI /Neoadjuvant chemotherapy /Immediate mpMRI /Cystectomy and Lymphadenectomy / Postoperative pathology Drug: Chemotherapy Procedure: Immediate Multiparametric MRI Procedure: Cystectomy and Lymphadenectomy | Drug: Chemotherapy<br>* Patients with muscle invasive bladder cancer will receive modified gemcitabine-cisplatin neoadjuvant chemotherapy prior to radical cystectomy for a period of two months (three 21 day cycles) as part of standard clinical routine.<br>* Other names: Neoadjuvant chemotherapy;Diagnostic Test: Immediate Multiparametric MRI<br>* Within 24 hours after the use of cisplatin during the first course of modified GC neoadjuvant chemotherapy, patient considered muscle invasive bladder cancer with baseline mpMRI will receive an immediate mpMRI scan.<br>* Other names: Multiparameter magnetic resonance imaging;Procedure: Cystectomy and Lymphadenectomy<br>* The patient with muscle invasive bladder cancer will undergo radical cystectomy and pelvic lymph node dissection followed by a urinary tract reconstruction.<br>* Other names: surgery;Diagnostic Test: conventional Multiparametric MRI<br>* After two and three course of neoadjuvant chemotherapy, patient considered muscle invasive bladder cancer with baseline mpMRI will receive a conventional mpMRI scan.<br>* Other names: Multiparameter magnetic resonance imaging;Diagnostic Test: Baseline Multiparametric MRI<br>* Patient considered muscle invasive bladder cancer will receive a baseline mpMRI scan within one week before neoadjuvant chemotherapy.<br>* Other names: Multiparameter magnetic resonance imaging;|
| Experimental: Experimental: Chemotherapy + surgery<br>Baseline mpMRI /Neoadjuvant chemotherapy /Cystectomy and Lymphadenectomy / Postoperative pathology Drug: Chemotherapy Procedure: Cystectomy and Lymphadenectomy | Drug: Chemotherapy<br>* Patients with muscle invasive bladder cancer will receive modified gemcitabine-cisplatin neoadjuvant chemotherapy prior to radical cystectomy for a period of two months (three 21 day cycles) as part of standard clinical routine.<br>* Other names: Neoadjuvant chemotherapy;Procedure: Cystectomy and Lymphadenectomy<br>* The patient with muscle invasive bladder cancer will undergo radical cystectomy and pelvic lymph node dissection followed by a urinary tract reconstruction.<br>* Other names: surgery;Diagnostic Test: conventional Multiparametric MRI<br>* After two and three course of neoadjuvant chemotherapy, patient considered muscle invasive bladder cancer with baseline mpMRI will receive a conventional mpMRI scan.<br>* Other names: Multiparameter magnetic resonance imaging;Diagnostic Test: Baseline Multiparametric MRI<br>* Patient considered muscle invasive bladder cancer will receive a baseline mpMRI scan within one week before neoadjuvant chemotherapy.<br>* Other names: Multiparameter magnetic resonance imaging;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline tumor mp-MRI parameters at immediate mp-MRI evaluation. | Using the built-in tools of the MRI imaging system to assess the changes of tumor size between immediate mp-MRI evaluation and baseline mp-MRI evaluation after the use of cisplatin during the first course of modified GC neoadjuvant chemotherapy. | baseline, during the intervention (Within 24 hours after use of cisplatin of the first course of neoadjuvant chemotherapy(NAC), up to 2 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline tumor mp-MRI parameters after two course of modified GC neoadjuvant chemotherapy. | Using the built-in tools of the MRI imaging system to assess the changes of tumor size conventional mp-MRI evaluation and baseline mp-MRI evaluation after the second course of modified GC neoadjuvant chemotherapy. | baseline, during the intervention(From the end date of the second course of NAC until one day before the third course of NAC, up to 7 weeks) | 
| Changes from baseline tumor mp-MRI parameters after three course of modified GC neoadjuvant chemotherapy. | Using the built-in tools of the MRI imaging system to assess the changes of tumor size between conventional mp-MRI evaluation and baseline mp-MRI evaluation after the third course of modified GC neoadjuvant chemotherapy. | baseline, during the intervention(From the end date of the third course of NAC until one day before surgery, up to 10 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiparametric Magnetic Resonance Imaging, Bladder Cancer, Chemotherapy