Transurethral En Bloc Versus Standard Resection of Bladder Tumour

• ClinicalTrials.gov Identifier: NCT02993211
• Recruitment Status: Recruiting
• First Posted: December 15, 2016
• Last Update Posted: January 27, 2021
• Sponsor: Chinese University of Hong Kong
• Collaborators: Kwong Wah Hospital; North District Hospital; Our Lady of Maryknoll Hospital; Pok Oi Hospital; The University of Hong Kong; Tseung Kwan O Hospital; Tuen Mun Hospital; Tung Wah Hospital; United Christian Hospital; Princess Margaret Hospital, Hong Kong; Caritas Medical Centre, Hong Kong; Queen Elizabeth Hospital, Hong Kong
• Information provided by (Responsible Party): Jeremy Yuen Chun TEOH, Chinese University of Hong Kong

Study Description

Brief Summary:

Conventionally, transurethral standard resection (SR) of bladder tumour is performed in a piecemeal manner. Transurethral en bloc resection (EBR) has been described as an alternate surgical technique in bladder tumour resection. By preventing tumour fragmentation and ascertaining complete tumour resection by histological assessment of the EBR specimen, we hypothesized that EBR could reduce disease recurrence as compared to SR.

Condition or disease	Intervention/treatment	Phase
Bladder Cancer	Device: Bipolar transurethral standard resection; Device: Bipolar transurethral en bloc resection	Phase 3

Detailed Description:

Bladder cancer is the 9th most commonly diagnosed cancer in men worldwide, with a standardized incidence rate of 9.0 per 100,000 person-years for men and 2.2 per 100,000 person-years for women. In Hong Kong, more than 400 new cases of bladder cancer are diagnosed every year. It is a common and important disease which carries a significant burden to the health medical system.

For patients who are diagnosed to have bladder tumours upon flexible cystoscopy, transurethral resection of bladder tumour (TURBT) should be offered. Being a minimally invasive procedure, it has become the standard for the initial management of bladder cancer. This operation aims to ascertain the diagnosis, to correctly stage the tumour (T-stage) and to cure the disease in the case of non-muscle-invasive bladder cancer (NMIBC). However, in a combined analysis of 2,596 patents from 7 randomised controlled trials in patients with NMIBC, it was shown that 1-year recurrence rate ranged from 15-61%, and 5-year recurrence rate ranged from 31-78%. Despite possible complete tumour resection during TURBT, the oncological control of NMIBC is far from satisfactory.

There are two main problems with the conventional standard resection (SR) procedure. First, the bladder tumour is resected in a piecemeal manner. This results in tumour fragmentation and floating tumour cells inside the bladder. The tumour cells may re-implant on to the bladder wall and lead to early disease recurrence. Second, 'complete tumour resection' is often determined by endoscopic vision only. Due to the inherited nature of piecemeal resection, it is not possible to assess the resection margin by histological means. The charring effect to the resection bed may also hinder the judgement of a 'complete tumour resection'. Routine second-look TURBT has been advocated for selected patients (Any presence of T1 disease, G3 disease, or any absence of detrusor muscle in the first TURBT specimen) even after a 'complete tumour resection' during the first TURBT. Second-look TURBT has been shown to detect residual disease in 33-55% of the patients and upstaging of disease in 4-45% of the patients. These results highlighted the limitations of TURBT in ascertaining complete tumour resection.

Transurethral en bloc resection (EBR) has been described as an alternate surgical technique in bladder tumour resection. By preventing tumour fragmentation and ascertaining complete tumour resection by histological assessment of the EBR specimen, we hypothesized that EBR could reduce disease recurrence as compared to SR.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 350 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Transurethral En Bloc Versus Standard Resection of Bladder Tumour: A Multi-centre Randomised Controlled Trial (EB-StaR Study).
• Actual Study Start Date: April 18, 2017
• Estimated Primary Completion Date: December 31, 2021
• Estimated Study Completion Date: December 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Standard resection; For patients undergoing bipolar transurethral standard resection, bladder tumour is resected in a piecemeal manner.	Device: Bipolar transurethral standard resection; Olympus TURis Bipolar HF-resection electrode (Model: WA22306D)
Experimental: En bloc resection; For patients undergoing bipolar transurethral en bloc resection, bladder tumour is resected and removed in one piece.	Device: Bipolar transurethral en bloc resection; Olympus TURis Bipolar HF-resection electrode (Model: WA22306D)

Outcome Measures

Primary Outcome Measures :

1. One-year recurrence rate [ Time Frame: One year after the allocated treatment ]
   Rate of disease recurrence one year after the operation

Secondary Outcome Measures :

1. Detrusor muscle sampling rate [ Time Frame: One week after the allocated treatment ]
   Rate of presence of detrusor muscle in the pathological specimen
2. Occurrence of obturator reflex [ Time Frame: Intra-operative ]
   Number of participants with obturator reflex encountered by the operating surgeon during the operation
3. Operative time [ Time Frame: Immediately post-operative ]
   Duration of operation
4. Rate of mitomycin C instillation [ Time Frame: One day after the allocated treatment ]
   Rate of mitomycin C instillation given after the operation
5. Hospital stay [ Time Frame: Three days after the allocated treatment ]
   Patients undergoing transurethral resection surgery have an average hospital stay of three days.
6. 30-day complications [ Time Frame: Thirty days after the allocated treatment ]
   Complications which occur within 30 days after the operation
7. Residual disease upon second look transurethral resection surgery [ Time Frame: Seven weeks after the allocated treatment ]
   Second look transurethral resection surgery is expected to perform within six weeks after the allocated treatment and one more week is allowed for histological assessment of the second look transurethral resection specimen. Residual disease is measured by the number of participants with the presence of urothelial carcinoma in the second look transurethral resection specimen.
8. Upstaging of disease upon second look transurethral resection surgery [ Time Frame: Seven weeks after the allocated treatment ]
   Second look transurethral resection surgery is expected to perform within six weeks after the allocated treatment and one more week is allowed for histological assessment of the second look transurethral resection specimen. Upstaging of disease is measured by the number of participants with upstaging of disease from non-muscle-invasive bladder cancer to muscle-invasive bladder cancer in the second look transurethral resection specimen.
9. One-year progression rate [ Time Frame: One year after the allocated treatment ]
   Rate of disease progression one year after the operation

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age ≥ 18 years old with informed consent

Exclusion Criteria:

• Bladder tumour base with maximal dimension of >3cm (Anticipated difficulty in retrieving the specimen en bloc)
• Bladder tumour detected during intravesical BCG therapy (BCG failure warrants more aggressive treatment, i.e. radical cystectomy)
• Histological diagnosis other than NMIBC
• Presence or prior history of upper urinary tract malignancy
• ECOG performance status ≥ 3 (Confined to bed or chair more than 50% of waking hours)
• ASA III or above (Patient with severe systemic disease)
• History of bleeding disorder or use of anti-coagulants
• Pregnancy
• Presence of other active malignancy
• Life expectancy of less than one year

Contacts and Locations

Contacts

Contact: Jeremy YC Teoh, FRCS(Ed) MBBS; +852 3505 2625; jeremyteoh@surgery.cuhk.edu.hk

Contact: Steven CH Leung, MSc; +852 3505 1663; stevenleung@surgery.cuhk.edu.hk

Locations

Hong Kong

Caritas Medical Centre; Recruiting

Hong Kong, Hong Kong

Contact: Yi Chiu

Principal Investigator: Yi Chiu

Sub-Investigator: Man-Chung Law

Sub-Investigator: Chun-Ki Chan

Sub-Investigator: Vincent YK Poon

Sub-Investigator: Chi-Ho Ip

Kwong Wah Hospital; Recruiting

Hong Kong, Hong Kong

Contact: Wing-Hong Chu

Principal Investigator: Wing-Hong Chu

Sub-Investigator: Chak-Lam Cho

Sub-Investigator: Kwun-Wai Chan

Sub-Investigator: In-Chak Law

Sub-Investigator: Clarence LH Leung

North District Hospital; Recruiting

Hong Kong, Hong Kong

Contact: Ho-Man Tam

Principal Investigator: Ho-Man Tam

Sub-Investigator: Jeremy YC Teoh

Sub-Investigator: Peter KF Chiu

Sub-Investigator: Hon-Ming Wong

Sub-Investigator: Joseph KM Li

Our Lady of Maryknoll Hospital; Recruiting

Hong Kong, Hong Kong

Contact: Chak-Lam Cho

Principal Investigator: Chak-Lam Cho

Sub-Investigator: Wing-Hong Chu

Sub-Investigator: Kwun-Wai Chan

Sub-Investigator: In-Chak Law

Sub-Investigator: Clarence LH Leung

Pok Oi Hospital; Recruiting

Hong Kong, Hong Kong

Contact: Tsz-Yeung Chan

Principal Investigator: Tsz-Yeung Chan

Sub-Investigator: Sau-Kwan Chu

Sub-Investigator: Chi-Wai Man

Sub-Investigator: Cheung-Hing Cheng

Sub-Investigator: Chris YK Lee

Prince of Wales Hospital; Recruiting

Hong Kong, Hong Kong

Contact: Jeremy YC Teoh

Principal Investigator: Jeremy YC Teoh

Sub-Investigator: Eddie SY Chan

Sub-Investigator: Peter KF Chiu

Sub-Investigator: Chi-Fai Ng

Sub-Investigator: Chi-Hang Yee

Sub-Investigator: Hon-Ming Wong

Sub-Investigator: Joseph KM Li

Princess Margaret Hospital; Recruiting

Hong Kong, Hong Kong

Contact: Yi Chiu

Principal Investigator: Yi Chiu

Sub-Investigator: Man-Chung Law

Sub-Investigator: Chun-Ki Chan

Sub-Investigator: Vincent YK Poon

Sub-Investigator: Chi-Ho Ip

Queen Elizabeth Hospital; Recruiting

Hong Kong, Hong Kong

Contact: Trevor CF Li

Principal Investigator: Trevor CF Li

Sub-Investigator: Chi-Man Ng

Sub-Investigator: Chung-Ting Pun

Sub-Investigator: Tsz-Leung Ng

Sub-Investigator: Chi-Fai Kan

Sub-Investigator: Ho-Yin Ngai

Sub-Investigator: Wai-Man Kan

Sub-Investigator: Wing-Hang Au

Queen Mary Hospital; Recruiting

Hong Kong, Hong Kong

Contact: Brian SH Ho

Principal Investigator: Brian SH Ho

Sub-Investigator: Chiu-Fung Tsang

Sub-Investigator: Ming-Kwong Yiu

Sub-Investigator: Terence CT Lai

Sub-Investigator: Wai-Kit Ma

Sub-Investigator: Ada TL Ng

Sub-Investigator: Charles KW Wong

Sub-Investigator: James HL Tsu

Tseung Kwan O Hospital; Recruiting

Hong Kong, Hong Kong

Contact: Bryan KC Cheng

Principal Investigator: Bryan KC Cheng

Sub-Investigator: Wilson HC Chan

Sub-Investigator: Kin-Man Lam

Tuen Mun Hospital; Recruiting

Hong Kong, Hong Kong

Contact: Sau-Kwan Chu

Principal Investigator: Sau-Kwan Chu

Sub-Investigator: Chi-Wai Man

Sub-Investigator: Tsz-Yeung Chan

Sub-Investigator: Cheung-Hing Cheng

Sub-Investigator: Chris YK Lee

Tung Wah Hospital; Recruiting

Hong Kong, Hong Kong

Contact: Chiu-Fung Tsang

Principal Investigator: Chiu-Fung Tsang

Sub-Investigator: Brian SH Ho

Sub-Investigator: Ming-Kwong Yiu

Sub-Investigator: Terence CT Lai

Sub-Investigator: Wai-Kit Ma

Sub-Investigator: Ada TL Ng

Sub-Investigator: Charles KW Wong

Sub-Investigator: James HL Tsu

United Christian Hospital; Recruiting

Hong Kong, Hong Kong

Contact: Wilson HC Chan

Principal Investigator: Wilson HC Chan

Sub-Investigator: Bryan KC Cheng

Sub-Investigator: Hing-Shing So

Sponsors and Collaborators

Chinese University of Hong Kong

Kwong Wah Hospital

North District Hospital

Our Lady of Maryknoll Hospital

Pok Oi Hospital

The University of Hong Kong

Tseung Kwan O Hospital

Tuen Mun Hospital

Tung Wah Hospital

United Christian Hospital

Princess Margaret Hospital, Hong Kong

Caritas Medical Centre, Hong Kong

Queen Elizabeth Hospital, Hong Kong

Investigators

• Principal Investigator: Jeremy YC Teoh, MBBS; Chinese University of Hong Kong

More Information

Publications:

Sylvester RJ, van der Meijden AP, Oosterlinck W, Witjes JA, Bouffioux C, Denis L, Newling DW, Kurth K. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol. 2006 Mar;49(3):466-5; discussion 475-7. Epub 2006 Jan 17.

Babjuk M, Böhle A, Burger M, Capoun O, Cohen D, Compérat EM, Hernández V, Kaasinen E, Palou J, Rouprêt M, van Rhijn BWG, Shariat SF, Soukup V, Sylvester RJ, Zigeuner R. EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016. Eur Urol. 2017 Mar;71(3):447-461. doi: 10.1016/j.eururo.2016.05.041. Epub 2016 Jun 17.

Grimm MO, Steinhoff C, Simon X, Spiegelhalder P, Ackermann R, Vogeli TA. Effect of routine repeat transurethral resection for superficial bladder cancer: a long-term observational study. J Urol. 2003 Aug;170(2 Pt 1):433-7.

Divrik RT, Sahin AF, Yildirim U, Altok M, Zorlu F. Impact of routine second transurethral resection on the long-term outcome of patients with newly diagnosed pT1 urothelial carcinoma with respect to recurrence, progression rate, and disease-specific survival: a prospective randomised clinical trial. Eur Urol. 2010 Aug;58(2):185-90. doi: 10.1016/j.eururo.2010.03.007. Epub 2010 Mar 19.

Jahnson S, Wiklund F, Duchek M, Mestad O, Rintala E, Hellsten S, Malmström PU. Results of second-look resection after primary resection of T1 tumour of the urinary bladder. Scand J Urol Nephrol. 2005;39(3):206-10.

Lazica DA, Roth S, Brandt AS, Böttcher S, Mathers MJ, Ubrig B. Second transurethral resection after Ta high-grade bladder tumor: a 4.5-year period at a single university center. Urol Int. 2014;92(2):131-5. doi: 10.1159/000353089. Epub 2013 Aug 23.

Vasdev N, Dominguez-Escrig J, Paez E, Johnson MI, Durkan GC, Thorpe AC. The impact of early re-resection in patients with pT1 high-grade non-muscle invasive bladder cancer. Ecancermedicalscience. 2012;6:269. doi: 10.3332/ecancer.2012.269. Epub 2012 Sep 18.

Ukai R, Kawashita E, Ikeda H. A new technique for transurethral resection of superficial bladder tumor in 1 piece. J Urol. 2000 Mar;163(3):878-9.

Kramer MW, Rassweiler JJ, Klein J, Martov A, Baykov N, Lusuardi L, Janetschek G, Hurle R, Wolters M, Abbas M, von Klot CA, Leitenberger A, Riedl M, Nagele U, Merseburger AS, Kuczyk MA, Babjuk M, Herrmann TR. En bloc resection of urothelium carcinoma of the bladder (EBRUC): a European multicenter study to compare safety, efficacy, and outcome of laser and electrical en bloc transurethral resection of bladder tumor. World J Urol. 2015 Dec;33(12):1937-43. doi: 10.1007/s00345-015-1568-6. Epub 2015 Apr 25.

• Responsible Party: Jeremy Yuen Chun TEOH, Assistant Professor, Chinese University of Hong Kong
• ClinicalTrials.gov Identifier: NCT02993211
• Other Study ID Numbers: CRE Ref. No. 2016.553
• First Posted: December 15, 2016
• Last Update Posted: January 27, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jeremy Yuen Chun TEOH, Chinese University of Hong Kong:

Bladder cancer; Transurethral resection; En bloc resection; TURBT

Additional relevant MeSH terms:

Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Urinary Bladder Diseases; Urologic Diseases