Evaluating the Impact of 18F-FDG-PET-CT on Risk Stratification and Treatment Adaptation for Patients With Muscle Invasive Bladder Cancer

Study Overview
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Brief Summary
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Evaluate the impact of 18F-FDG-PET-CT on the staging of patients with muscle invasive bladder cancer. Based on the results of 2 18F-FDG-PET-CT's patients are stratified in non-metastatic, oligometastatic and polymetastatic bladder cancer patients and the treatment is adapted accordingly to improve overall survival.

Official Title
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Evaluating the Impact of 18F-FDG-PET-CT on Risk Stratification and Treatment Adaptation for Patients With Muscle Invasive Bladder Cancer (EFFORT-MIBC): A Phase II Prospective Trial

Conditions
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Muscle-Invasive Bladder Carcinoma

Intervention / Treatment
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* Radiation: Metastasis directed therapy (MDT)
* Drug: Immunotherapy
* Procedure: Standard of care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathology-proven MIBC on TURb or ≥ T3 on conventional imaging treated with MIBC radical treatment T1-4 N0-3 M0 MIBC on conventional imaging (thoracic CT and abdominopelvic CT/ MRI) Age > 18 years WHO 0-2 Willingness to undergo 18F-FDG-PET-CT Willingness to undergo MDT or immunotherapy, in case of diagnosis of oligometastatic or polymetastatic disease on 18F-FDG-PET-CT, respectively Willingness and ability to provide a signed informed consent according to ICH/GCP and national/local regulations Exclusion Criteria: Presence of distant metastasis on conventional imaging (thoracic CT and abdominopelvic CT/ MRI) Refusal of or having contraindications to 18F-FDG-PET-CT Refusal of MDT or immunotherapy Prior radiotherapy unabling MDT Contraindications to radiotherapy (including active inflammatory bowel disease) Contraindications to immunotherapy Other primary tumor diagnosed < 5 years ago and for which treatment is still required, except for diagnosis of non-metastatic prostate cancer at time of diagnosis of MIBC or non-melanoma skin cancer.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Non-metastatic MIBC<br>No signs of extra-pelvic metastasis on conventional imaging (abdominopelvic and thoracic CT/MRI) and 18F-FDG-PET-CT's | Procedure: Standard of care<br>* Patient receives standard of care therapy with either radical cystectomy with pelvic lymph node dissection or trimodality therapy (consisting of a visible complete TURb and radio chemotherapy). Afterwards regular follow up is performed.<br>|
| Experimental: Oligo-metastatic MIBC on 18F-FDG-PET-CT<br>No signs of extra-pelvic metastasis on conventional imaging (abdominopelvic and thoracic CT/MRI) but presence of ≤ 3 metastasis on 1 or both 18F FDG PET-CT 's | Radiation: Metastasis directed therapy (MDT)<br>* Patient receives standard of care therapy with either radical cystectomy with pelvic lymph node dissection or trimodality therapy (consisting of a visible complete TURb and radio chemotherapy). Concurrently, the oligometastasis will be treated with stereotactic body radiotherapy or metastasectomy.<br>|
| Experimental: Poly-metastatic MIBC on 18F-FDG-PET-CT<br>No signs of extra-pelvic metastasis on conventional imaging (abdominopelvic and thoracic CT/MRI) but presence of > 3 metastasis on 1 or both 18F FDG PET-CT 's | Drug: Immunotherapy<br>* Patient receives standard of care therapy with either radical cystectomy with pelvic lymph node dissection or trimodality therapy (consisting of a visible complete TURb and radio chemotherapy). Afterwards immunotherapy will be initiated and regular follow up will be performed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Defined as the time from diagnosis of MIBC to death from any cause | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of patients with acute toxicity | Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | 3 months | 
| The number of patients with late toxicity | Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | 5 years | 
| Progression-free survival | Defined as appearance of local/locoregional recurrence diagnosed at CT-scan or cystoscopy in case of TMT or appearance of metastasis diagnosed at MIBC or non-MIBC-related imaging. | 5 years | 
| Distant metastasis-free survival | Defined as time of diagnosis until occurrence of distant metastasis on repeated imaging. | 5 years | 
| Disease specific survival | Defined as time of diagnosis until death due to MIBC. | 5 years | 
| Patient reported quality of life as per EORTC-QLQ C30 | Validated questionnaire assessing different health-related parameters (psychological, physical and social well-being) in cancer patients | 5 years | 
| Patient reported quality of life as per EORTC-QLQ BLM30 | Validated questionnaire assessing the health-related QOL of muscle invasive bladder cancer patients | 5 years | 
| Sensitivity/specificity of 18F-FDG-PET-CT for the detection of extra-pelvic metastases | Sensitivity/specificity of 18F-FDG-PET-CT | 3 months | 
| Validation of predictive biomarkers | A biopsy specimen of the bladder, obtained after transurethral resection of the bladder (TURb),as well as urine and blood samples will be collected for validation of predictive biomarkers by evaluating the correlation between response to therapy and outcome (PFS, DMFS, DSS and OS) with in literature reported biomarkers determined on biopsy specimen of the bladder, obtained after TURb. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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18F-FDG-PET-CT, Staging, Distand metastasis, Oligometastatic disease, Metastasis directed therapy, Immunotherapy