Transurethral En Bloc Versus Standard Resection of Bladder Tumour

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Transurethral En Bloc Versus Standard Resection of Bladder Tumour: A Multi-centre Randomised Controlled Trial (EB-StaR Study).

Conditions
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Bladder Cancer

Intervention / Treatment
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* Device: Bipolar transurethral standard resection
* Device: Bipolar transurethral en bloc resection


Participation Criteria
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Eligibility Criteria
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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

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
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| One-year recurrence rate | Rate of disease recurrence one year after the operation | One year after the allocated treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detrusor muscle sampling rate | Rate of presence of detrusor muscle in the pathological specimen | One week after the allocated treatment | 
| Occurrence of obturator reflex | Number of participants with obturator reflex encountered by the operating surgeon during the operation | Intra-operative | 
| Operative time | Duration of operation | Immediately post-operative | 
| Rate of mitomycin C instillation | Rate of mitomycin C instillation given after the operation | One day after the allocated treatment | 
| Hospital stay | Patients undergoing transurethral resection surgery have an average hospital stay of three days. | Three days after the allocated treatment | 
| 30-day complications | Complications which occur within 30 days after the operation | Thirty days after the allocated treatment | 
| Residual disease upon second look transurethral resection surgery | 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. | Seven weeks after the allocated treatment | 
| Upstaging of disease upon second look transurethral resection surgery | 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. | Seven weeks after the allocated treatment | 
| One-year progression rate | Rate of disease progression one year after the operation | One year after the allocated treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transurethral resection, En bloc resection, TURBT, Bladder cancer