Open Vs Robotic-Assisted Radical Cystectomy: A Randomized Trial

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).

Study Overview

• Status: Completed
• Conditions: Bladder Cancer Requiring Cystectomy
• Intervention / Treatment: Procedure: Open radical cystectomy; Procedure: Robotic assisted radical cystectomy; Device: DaVinci robot

• Study Type: Interventional
• Enrollment (Actual): 350
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
  • California
    • Orange, California, United States, 92868
      • University of California, Irvine Medical Center (UC Irvine)
    • Stanford, California, United States, 94305
      • Stanford University
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • The University of Texas Health Science Center at San Antonio, Medical Arts & Research Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health Science Center, Department of Urology
  • Washington
    • Seattle, Washington, United States, 98101
      • Cancer Research and Biostatistics (Data Management and Statistical Office)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient must have biopsy proven bladder cancer. Official pathology report reviewed at the participating institution is required.
2. Bladder cancer must be clinical stage T1-T4, N0-1, M0. (AJCC 7th edition) or refractory cis (carcinoma in situ).

Exclusion Criteria:

1. Inability to give informed consent.
2. Prior major abdominal and pelvic open surgical procedures that would preclude a safe robotic approach, as determined by the treating surgeon.
3. 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.
4. Age <18 or >99 years.
5. Pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Miami
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Dipen J Parekh, MD, University of Miami

Publications and helpful links

General Publications

• Venkatramani V, Reis IM, Gonzalgo ML, Castle EP, Woods ME, Svatek RS, Weizer AZ, Konety BR, Tollefson M, Krupski TL, Smith ND, Shabsigh A, Barocas DA, Quek ML, Dash A, Parekh DJ. Comparison of Robot-Assisted and Open Radical Cystectomy in Recovery of Patient-Reported and Performance-Related Measures of Independence: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2022 Feb 1;5(2):e2148329. doi: 10.1001/jamanetworkopen.2021.48329.
• Parekh DJ, Reis IM, Castle EP, Gonzalgo ML, Woods ME, Svatek RS, Weizer AZ, Konety BR, Tollefson M, Krupski TL, Smith ND, Shabsigh A, Barocas DA, Quek ML, Dash A, Kibel AS, Shemanski L, Pruthi RS, Montgomery JS, Weight CJ, Sharp DS, Chang SS, Cookson MS, Gupta GN, Gorbonos A, Uchio EM, Skinner E, Venkatramani V, Soodana-Prakash N, Kendrick K, Smith JA Jr, Thompson IM. Robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer (RAZOR): an open-label, randomised, phase 3, non-inferiority trial. Lancet. 2018 Jun 23;391(10139):2525-2536. doi: 10.1016/S0140-6736(18)30996-6.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (ACTUAL): December 1, 2018
• Study Completion (ACTUAL): December 1, 2018

Study Registration Dates

• First Submitted: June 30, 2010
• First Submitted That Met QC Criteria: July 5, 2010
• First Posted (ESTIMATE): July 7, 2010

Study Record Updates

• Last Update Posted (ACTUAL): November 3, 2020
• Last Update Submitted That Met QC Criteria: October 30, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: bladder cancer; open cystectomy; robotic assisted radical cystectomy
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: 20120408; R01CA155388 (NIH); 36911 (OTHER: Investigator-Assigned ID)