Open Vs Robotic-Assisted Radical Cystectomy: A Randomized Trial

Study Overview
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Brief Summary
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This is a multi-institutional, randomized trial evaluating oncologic, perioperative, and functional outcomes following two standard care procedures for radical cystectomy. The participants will have one of the standard care procedures as part of their care. The two procedures that will be followed are open radical cystectomy and robotic assisted radical cystectomy (RARC). Open cystectomy is considered to be the more traditional approach. While newer, RARC is considered to be equivalent to open surgery when it is performed by a trained robotics surgeon. The reported complication rates of RARC appear comparable to open surgery. This means there is no significant difference in the risk between the two standard procedures. However, despite these potential advantages, true comparison between the open and robotic technique with regards to long term cancer related and functional outcomes has not been accomplished because previous studies did not compare patients of equal health status. The researchers hope to learn whether or not patients undergoing RARC recover more quickly than or at the same rate as patients undergoing an open radical cystectomy while having non inferior cancer related outcomes. This study is funded by the National Institutes of Health (NIH).

Official Title
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Open Vs Robotic-Assisted Radical Cystectomy: A Randomized Trial

Conditions
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Bladder Cancer Requiring Cystectomy

Intervention / Treatment
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* Procedure: Open radical cystectomy
* Procedure: Robotic assisted radical cystectomy
* Device: DaVinci robot


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must have biopsy proven bladder cancer. Official pathology report reviewed at the participating institution is required. Bladder cancer must be clinical stage T1-T4, N0-1, M0. (AJCC 7th edition) or refractory cis (carcinoma in situ). Exclusion Criteria: Inability to give informed consent. Prior major abdominal and pelvic open surgical procedures that would preclude a safe robotic approach, as determined by the treating surgeon. At the discretion of the treating surgeon, any pre-existing condition such as severe chronic obstructive pulmonary disease that precludes a safe initiation or maintenance of pneumoperitoneum over a prolonged period of time and during surgery. Age <18 or >99 years. Pregnancy.

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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Non inferiority phase 3 randomized clinical trial comparing robotic to open radical cystectomy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Open cystectomy<br>Open cystectomy performed using an incision made just above or at the level of umbilicus to the pubic symphysis. | Procedure: Open radical cystectomy<br>* Standard of care removal of urinary bladder.<br>|
| Active Comparator: Robotic assisted radical cystectomy<br>Robotic assisted Radical Cystectomy (RARC) is accomplished by a robot assisted laparoscopic approach. | Procedure: Robotic assisted radical cystectomy<br>* Standard of care removal of urinary bladder using DaVinci robot.<br>Device: DaVinci robot<br>* DaVinci robotic surgical system.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With 2-year Progression Free Survival (PFS) | Progression will be determined by the treating physician using the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria based on radiographic or pathological evidence of disease progression or death from disease. | 24 months | 
| Number of Participants With Positive Margins | Evaluated are the number of participants with positive surgical, bladder, and urethral margins. Positive margin is defined as presence of tumor cells at the edge of the dissected tissue. | At time of cystectomy, approximately 1 hour. | 
| Number of Participants Requiring Lymph Node Dissection | Evaluated are the number of participants requiring extended or standard lymph node dissection | At time of cystectomy, approximately 1 hour | 
| Quality of Life (QOL) Outcomes | Functional Assessment of Cancer Therapy- Vanderbilt Cystectomy Index (FACT-VCI) scores range is 0-168 which is sum of physical, emotional, wellbeing, and FACTS Bl Cys. higher scores=better QOL. | at baseline, 3 month, and 6 months | 
| Number of Participants With Post-surgical Complications | Post surgical complications will be evaluated using the Clavien grading system with scores ranging from 0-5 with the higher number indicating increased post-surgical complications. | 90 days post operative | 
| Amount of Estimated Blood Loss (EBL) in ml | Perioperative measures such as EBL will be evaluated by measuring the amount of participant blood loss in ml. | At time of cystectomy, approximately 1 hour | 
| Number of Participants Requiring Blood Transfusion | Number of participants requiring peri, intra, and post operative blood transfusion. | At time of cystectomy, approximately 1 hour | 
| Number of Days of Post Operative Length of Hospital Stay | Number of days of post operative length of hospital stay will be evaluated | Day 10 post surgery | 
| Length of Operative Time | Length of minutes of cystectomy procedure | At time of cystectomy, approximately 1 hour | 
| Laboratory Values | Serum Hemoglobin (Hb) and Albumin will be reported in grams per deciliters (g/dL) | baseline, 6 weeks, 3 months, 6 months, 12 months, 24 months, 36 months | 
| Measures of Functional Independence as Assessed by the Activities of Daily Living (ADL) Questionnaire | Participant reported ADL questionnaire is a 7 item questionnaire with scores ranging from 7-21 with a lower score indicating increased independence. | baseline, 1 month , 3 months, 6 months | 
| Percentage of Participants With 3-year Progression Free Survival (PFS) | Progression will be determined by the treating physician using the RECIST Version 1.1 criteria based on radiographic or pathological evidence of disease progression or death from disease. | 3 years | 
| Quality of Life (QOL) Outcomes as Assessed by the Short Form 8 (SF-8) Questionnaire | The SF-8 consists of two component summary scores; physical (PCS) and mental component summary (MCS). They are scored by weighting each score to a norm-based scoring model. The total scores will be reported as a percentile with higher score indicating better quality of health. | baseline, 3 month, and 6 month | 
| Total Number of Participants Requiring Intra-operative Fluid Requirement | Total number of participants requiring Intra-operative fluid requirement. (blood+plasma+platelets) Note: In robotic group 1 participant received both plasma and platelets and 1 other received platelets in addition to blood transfusion. In the open group 5 participants received plasma in addition to blood transfusion. | At time of cystectomy, approximately 1 hour | 
| Total Postoperative Analgesic Requirements | Total postoperative analgesic requirements in milli grams | At time of cystectomy, approximately 1 hour | 
| Creatinine Value. | Serum creatinine will be reported in milligrams per deciliters (mg/dL). | baseline, 6 weeks, 3 months, 6 months, 12 months, 24 months, 36 months | 
| Measures of Functional Independence as Assessed by the Instrumental Activities of Daily Living (IADL) Questionnaire | Participant reported IADL questionnaire is an 8 item questionnaire with scores ranging from 8-32 with a lower score indicating increased independence. | baseline, 1 month, 3 months, 6 months | 
| Performance Related Measures of Functional Independence as Assessed by the Hand Grip Strength Test | The hand grip strength test is measured in kilograms of pressure using a handheld dynamometer. | baseline, 1 month, 3 months, 6 months | 
| Performance Related Measures of Functional Independence as Assessed by the Time Up and Go (TUG) Walking Test | The TUG test is measured in seconds. Patients will be timed as they rise from a standard chair, walk 3 meters, turn, walk back, and sit again. | baseline, 1 month, 3 months, 6 months | 
| Quality of Life (QOL) Outcomes as Assessed by the Functional Assessment of Cancer Therapy - Vanderbilt Cystectomy Index (FACT-VCI) Questionnaire | FACT-VCI consists of eight domains: Five subscale scores (physical wellbeing, social wellbeing, emotional wellbeing, functional wellbeing, and FACT for patients with Bladder Cancer following Cystectomy [FACT-BL-Cys]) and three derived scores (trial outcome index), FACT-General form (FACT-G), and FACT-BL-Cys Total.The ranges of scores for each domain are as follows: 0-28 for physical, social, and functional wellbeing; 0-24 for emotional wellbeing; 0-60 for FACT-BL-Cys; 0-116 for FACT-VCI Trial Outcome Index (sum of physical wellbeing, functional wellbeing, and FACT-BL-Cys scores); 0-108 for FACT-G (sum of physical, social, emotional, and functional wellbeing scores); and 0-168 for FACT-BL-Cys Total (sum of physical, social, emotional, and functional wellbeing scores, and FACT-BL-Cys).The higher score indicates increased wellbeing. | baseline, 3 months, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cost | Fixed and variable costs associated with the procedure. | Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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open cystectomy, robotic assisted radical cystectomy, bladder cancer