Open Versus Robot Assisted Radical Cystectomy With Totally Intracorporeal Urinary Diversion.

Open Versus Robot Assisted Radical Cystectomy With Totally Intracorporeal Urinary Diversion. Single Centre Prospective Randomized Trial.

This prospective randomized study is designed to provide high level of evidence supporting superiority of robot assisted (RA) versus open (O) radical cystectomy (RC). The primary endpoint is a 50% reduction of transfusion rate, several perioperative outcomes potentially linked to a reduced invasiveness are considered as secondary endpoints. Investigators hypothesis is that the reduced invasiveness of RARC might turn into a higher adherence to enhanced recovery after surgery (ERAS) protocols (early bowel recovery, reduced need for painkillers and insertion of nasogastric tube) and consequently to shorter hospital stay and to faster return to daily activities. These data will be taken into account in a matched cost analysis between arms. Secondary aims include a between arm matched comparison of perioperative complications, oncologic outcomes (2-yr disease free survival is an accepted surrogate of long term oncologic effectiveness of RC) and functional outcomes (daytime and nighttime continence).

Study Overview

• Status: Completed
• Conditions: Bladder Cancer
• Intervention / Treatment: Procedure: Open or robotic radical cystectomy

Detailed Description

Despite encouraging data deriving from colorectal surgery, evidences in favor to ERAS protocols following RARC are poor. Moreover, according to a recent survey of surgeons with a specialist interest in RC, the adherence to ERAS protocols is <20% [1].

Retrospective and preliminary data from the robotic consortium have supported oncologic effectiveness of RARC; however in the only prospective randomized trial comparing RARC and ORC urinary diversions were performed extracorporeally, potentially impairing the benefits of minimally invasive surgery [2].

Robot assisted radical cystectomy (RARC) has the aim of providing adequate cancer control while minimizing invasiveness of open radical cystectomy (ORC). The primary end-point of this trial is to demonstrate a reduction of perioperative transfusion rate in RARC arm by 50% compared to ORC arm.

ERAS protocols may significantly contribute to shortening length of hospital stay, a key outcome in this clinical setting of patients receiving RC, being the mean length of hospital stay around 14 days in Italy. Investigators' hypothesis is that the reduced invasiveness of RARC might contribute to an increased adoption of ERAS protocols (reduced need for reinsertion of nasogastric tube, shorter time to first flatus, to mobilization, to regular diet and finally shorter duration of hospital stay).

Assessment of oncologic outcomes of RARC, although not the primary endpoint of the present study, is certainly an outcome of interest. The expected duration of enrollment (18 mo) should provide 2-yr oncologic outcomes for about 66% of patients. Two-year recurrence free survival has been reported as a valid surrogate marker of long term oncologic survival after RC.

Specific Aim 1:To demonstrate superiority of RARC versus ORC in terms of 50% reduction of perioperative transfusion rates.

Specific Aim 2:

To evaluate invasiveness of both surgical approaches by assessing the adherence to ERAS protocols in both and the incidence of perioperative and 30-d, 90d, 180d complications, readmission rates (30d, 90d). Cost analysis will assess the potential impact of shorter hospital stay on overall costs of robotic procedures.

Specific Aim 3:

To assess quality of life at 6-mo, 12-mo and 24-mo follow-up evaluation and to perform a matched comparison of oncologic and functional outcomes between two arms.

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Lazio
    • Rome, Lazio, Italy, 00144
      • Regina Elena NCI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with muscle invasive high grade urothelial carcinoma (and variant histologies) of the bladder or high grade non muscle invasive BCG recurrent/refractory disease.

Exclusion Criteria:

• Cystectomy without curative intent (palliative, salvage).
• Patients unfit for robotic cystectomy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Open Radical Cystectomy; Open Radical Cystectomy, pelvic lymph node dissection, urinary diversion (neobladder or ileal conduit)	Procedure: Open or robotic radical cystectomy; ORC and orthotopic ileal neobladder is performed as previously described. A separate package PLND is performed as in open as in robotic surgery. RARC is performed replicating open surgical procedure. The orthotopic ileal neobladder model used is the 'vescica ileale padovana' as previously described. An ileal segment, approximately 42 cm long, is chosen at a minimum distance of 20cm far from ileo-cecal valve. A latero-lateral ileal anastomosis is performed with staplers to restore bowel continuity. For ileal conduit, a 20cm ileal segment (approximately 20 cm long) at a minimum distance of 20 cm from ileo-cecal valve is isolated and transected with staplers. Bowel continuity is restored as previously described. The ileal loop on its distal edge is extracted through abdomen wall at the previously identified stoma point and fixed to abdomen fascia. The ureters are spatulated and a latero-lateral anastomosis according to Wallace 1 technique is performed.
Experimental: Robot assisted radical cystectomy; Robot assisted radical cystectomy, pelvic lymph node dissection, intracorporeal urinary diversion (neobladder or ileal conduit)	Procedure: Open or robotic radical cystectomy; ORC and orthotopic ileal neobladder is performed as previously described. A separate package PLND is performed as in open as in robotic surgery. RARC is performed replicating open surgical procedure. The orthotopic ileal neobladder model used is the 'vescica ileale padovana' as previously described. An ileal segment, approximately 42 cm long, is chosen at a minimum distance of 20cm far from ileo-cecal valve. A latero-lateral ileal anastomosis is performed with staplers to restore bowel continuity. For ileal conduit, a 20cm ileal segment (approximately 20 cm long) at a minimum distance of 20 cm from ileo-cecal valve is isolated and transected with staplers. Bowel continuity is restored as previously described. The ileal loop on its distal edge is extracted through abdomen wall at the previously identified stoma point and fixed to abdomen fascia. The ureters are spatulated and a latero-lateral anastomosis according to Wallace 1 technique is performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants requiring perioperative transfusions.	50% reduction of perioperative transfusion rates in robotic arm.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants requiring insertion of nasogastric tube	Comparison between open and robotic arms.	30 days
Incidence of Clavien grade 1-2 perioperative complications at 30-d evaluation.	Comparison between open and robotic arms.	30 days
Incidence of Clavien grade 1-2 perioperative complications at 90-d evaluation.	Comparison between open and robotic arms.	90 days
Incidence of Clavien grade 1-2 perioperative complications at 180-d evaluation.	Comparison between open and robotic arms.	180 days
Incidence of patients requiring readmission.	Comparison between open and robotic arms.	90 days
Cost analysis.	Comparison between open and robotic arms.	30 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of quality of life at 6-mo follow-up with self-administered EORTC QLQ-BLM30 questionnaire	Comparison between open and robotic arms.	6 months
Assessment of quality of life at 6-mo follow-up with self-administered EORTC QLQ-C30 questionnaire	Comparison between open and robotic arms.	6 months
Assessment of quality of life at 12-mo follow-up with self-administered EORTC QLQ-BLM30 questionnaire	Comparison between open and robotic arms.	12 months
Assessment of quality of life at 12-mo follow-up with self-administered EORTC QLQ-C30 questionnaire	Comparison between open and robotic arms.	12 months
Assessment of quality of life at 24-mo follow-up with self-administered EORTC QLQ-BLM30 questionnaire	Comparison between open and robotic arms.	24 months
Assessment of quality of life at 24-mo follow-up with self-administered EORTC QLQ-C30 questionnaire	Comparison between open and robotic arms.	24 months
Disease free survival	Comparison between open and robitic arms	24 months
Cancer specific survival	Comparison between open and robitic arms	24 months
Overall survival	Comparison between open and robitic arms	24 months
Assessment of urinary continence with pad test.	Comparison between open and robotic arms	12 months
Assessment of urinary continence with pad test.	Comparison between open and robotic arms	24 months

Collaborators and Investigators

• Sponsor: Regina Elena Cancer Institute
• Collaborators: Ministero della Salute, Italy
• Investigators: Principal Investigator: Giuseppe Simone, PhD, "Regina Elena" National Cancer Institute, Dept of Urology

Publications and helpful links

General Publications

• Mastroianni R, Tuderti G, Anceschi U, Bove AM, Brassetti A, Ferriero M, Zampa A, Giannarelli D, Guaglianone S, Gallucci M, Simone G. Comparison of Patient-reported Health-related Quality of Life Between Open Radical Cystectomy and Robot-assisted Radical Cystectomy with Intracorporeal Urinary Diversion: Interim Analysis of a Randomised Controlled Trial. Eur Urol Focus. 2022 Mar;8(2):465-471. doi: 10.1016/j.euf.2021.03.002. Epub 2021 Mar 10.

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2018
• Primary Completion (Actual): October 30, 2020
• Study Completion (Actual): September 30, 2022

Study Registration Dates

• First Submitted: January 26, 2018
• First Submitted That Met QC Criteria: February 8, 2018
• First Posted (Actual): February 15, 2018

Study Record Updates

• Last Update Posted (Actual): January 19, 2023
• Last Update Submitted That Met QC Criteria: January 18, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Open Radical Cystectomy; Robotic Radical cystectomy; Intracorporeal urinary diversion; Prospective randdomized trial
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: GR2016-02364306

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No