Evaluating Safety and Efficacy of Prostate-sparing Radical Cystectomy

Study Overview
=================
Brief Summary
-----------------
The purpose of this clinical trial is to determine if prostate-capsule-sparing cystectomy improves functional outcomes without comprising oncologic outcomes in male patients receiving a radical cystectomy. Patients will be randomized to one of two groups: prostate capsule-sparing radical cystectomy or nerve-sparing radical cystectomy. Patients will be monitored following standard of care guidelines and clinical data will be collected. Patients in both groups will be asked to complete an erectile function questionnaire at multiple timepoints. Patients who receive an orthotopic neobladder will be asked to complete a questionnaire to monitor urinary function at multiple timepoints. Patient adverse events will be monitored to ensure patients safety.

Detailed Description
-----------------
The purpose of this study is to determine if prostate capsule-sparing cystectomy improves functional outcomes without compromising the oncologic outcomes in patients with bladder cancer. The comparison arm will be patients undergoing nerve-sparing radical cystectomy. Participants will be randomized to receive either a nerve-sparing radical cystectomy or a prostate capsule-sparing radical cystectomy. Patients will be monitored following standard of care guidelines every 3-months post-operatively up to and including 24 months post-operatively. As part of standard of care post-operative follow-up patients will have routine history and physical exams, urine cytology, urine culture, Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), and Prostate Specific Antigen (PSA). Standard of Care diagnostic imaging will also occur. The Sexual Health Inventory for Men (SHIM) Questionnaire will be given to patients 6-weeks post-operatively and every 3-months post-operatively up to and including 24-months post-operatively. To measure urinary function in patients who receive orthotopic neobladder, the Validated Pad Questionnaire will be given 6-weeks post-operatively and every 3-months post-operatively up to and including 24-months post operatively. Adverse Events will be monitored in both groups as defined by the CTCAE 5.0 guidelines.

Official Title
-----------------
A Prospective, Randomized Trial Comparing Prostate Capsule-sparing and Nerve-sparing Radical Cystectomy in Patients With Bladder Cancer

Conditions
-----------------
Bladder Cancer

Intervention / Treatment
-----------------
* Procedure: Prostate capsule-sparing radical cystectomy
* Procedure: Nerve sparing radical cystectomy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects with pathologically confirmed bladder cancer scheduled for radical cystectomy Variant histologies of bladder cancer permitted Neoadjuvant therapy permitted Age > 18 years old Ability to understand and willingness to sign a written informed consent document Exclusion Criteria: Patients that are not candidates for cystectomy Moderate to severe erectile dysfunction with SHIM score <17 Bladder cancer with bladder neck or prostatic involvement, including cancer in the prostatic urethra Prior pelvic radiation Confirmed prostate cancer: Patients with abnormal Digital rectal exam (DRE), PSA >3 or Prostate Imaging Reporting & Data System (PIRADS) 4 lesions on prostate Multiparametric MRI (mpMRI) will undergo prostate biopsy to rule out prostate cancer Increased genetic risk of prostate cancer per National Comprehensive Cancer Network (NCCN) guidelines: ≥1 first-, second-, or third-degree relative with: breast cancer at age ≤50 y, colorectal or endometrial cancer at age ≤50 y, male breast cancer at any age, ovarian cancer at any age, exocrine pancreatic cancer at any age, metastatic, regional, very-high-risk, high-risk prostate cancer at any age ≥1 first-degree relative (father or brother) with: prostate cancer at age ≤60 y ≥2 first-, second-, or third-degree relatives with: breast cancer at any age, prostate cancer at any age ≥3 first- or second-degree relatives with: Lynch syndrome-related cancers, especially if diagnosed Patients with Lynch syndrome

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Prostate Capsule-Sparing Radical Cystectomy<br>Patients randomized to this arm will receive the prostate capsule-sparing surgery performed in the form of standard simple prostatectomy. Patients will also have a cystectomy with one of the following urinary diversions: ileal conduit, Indiana Pouch, or orthotopic neobladder. | Procedure: Prostate capsule-sparing radical cystectomy<br>* Patients randomized to this arm will receive the prostate capsule-sparing surgery performed in the form of standard simple prostatectomy. Patients will also have a cystectomy with one of the following urinary diversions: ileal conduit, Indiana Pouch, or orthotopic neobladder.<br>|
| Other: Nerve-Sparing Radical Cystectomy<br>Patients randomized to this arm will receive the nerve-sparing surgery will be performed in the form of the standard nerve-sparing radical prostatectomy. Patients will also have a cystectomy with one of the following urinary diversions: ileal conduit, Indiana Pouch, or orthotopic neobladder. | Procedure: Nerve sparing radical cystectomy<br>* Patients randomized to this arm will receive the nerve-sparing surgery will be performed in the form of the standard nerve-sparing radical prostatectomy. Patients will also have a cystectomy with one of the following urinary diversions: ileal conduit, Indiana Pouch, or orthotopic neobladder.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Functional Outcomes as assessed by the Sexual Health Inventory for Men (SHIM) | Comparison of functional outcomes focusing on preservation of erectile function in patients undergoing cystectomy for bladder cancer. Functional Outcomes will be measured by the Sexual Health Inventory for Men (SHIM) Questionnaire. The Sexual Health Inventory for Men defines the following ranges of Erectile Dysfunction (ED): 1-7 is Severe ED, 8-11 Moderate ED, 12-16 Mild to Moderate ED, and 17 to 21 is Mild ED. | Baseline, 6 weeks-post operatively, 3-months post-operatively, 6-months post-operatively, 9-months post-operatively, 12-months post-operatively, 15-months post-operatively, 18-months post-operatively, 21-months post-operatively, 24-months post-op | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in urinary function in patients with orthotopic neobladder as assessed by the Validated Pad Questionnaire | Urinary function in patient with orthotopic neobladder urinary diversions measured using the Validated Pad Questionnaire. The Validated Pad questionnaire will be used to determine the percentage of patients utilizing 1 to 2 pads versus 2 or more pads for night and day, respectively. | Baseline, 6 weeks-post operatively, 3-months post-operatively, 6-months post-operatively, 9-months post-operatively, 12-months post-operatively, 15-months post-operatively, 18-months post-operatively, 21-months post-operatively , 24-months post-op | 
| Change in overall patient survival | Comparing the overall survival of patients in both arms of the study | Baseline, 6 weeks-post operatively, 3-months post-operatively, 6-months post-operatively, 9-months post-operatively, 12-months post-operatively, 15-months post-operatively, 18-months post-operatively, 21-months post-operatively, 24-months post-op | 
| Change in disease specific status | Comparing the status of disease specific in both arms of the study | Baseline, 6 weeks-post operatively, 3-months post-operatively, 6-months post-operatively, 9-months post-operatively, 12-months post-operatively, 15-months post-operatively, 18-months post-operatively, 21-months post-operatively, 24-months post-op | 
| Soft tissue surgical margin rate as assessed by pathology | Pathologists will examine the soft tissue surgical margin rate to determine positive or negative soft tissue surgical margin. | Up to 4-weeks after surgical intervention | 
| Safety as assessed by adverse events experienced by study participants | Comparing the differences in adverse events (grades 2-5) as experienced by the participants of in each study arm. The grading of adverse events are defined by the CTCAE 5.0 guidelines. | Up to 24-months post-operative | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Radical Cystectomy, Prostate Capsule-Sparing Cystectomy, Nerve-Sparing Cystectomy, Male