Role of ERBT Plus Intravesical BCG in Intermediate-Risk or High-Risk NMBC

Official title

A Randomised Trial Investigating the Role of Transurethral En Bloc Resection of Bladder Tumour Plus Intravesical Bacillus Calmette-Guerin Therapy, in Patients With Intermediate-Risk or High-Risk Non-Muscle-Invasive Bladder Cancer

Overview

This is a prospective, multi-centre randomised trial comparing between cTURBT plus 1-year BCG therapy, and ERBT plus 1-year BCG therapy, in patients with intermediate-risk or high-risk NMIBC.

Detailed description

All patients who are diagnosed to have bladder tumour(s) upon flexible cystoscopy will be screened for study eligibility. Imaging will be arranged to rule out any upper urinary tract malignancy. Patients are randomised to receive either transurethral ERBT or cTURBT with an allocation ratio of 1:1. A single dose of intravesical mitomycin C will be instilled according to the EAU guidelines, i.e. in all patients except those with a prior recurrence rate of more than one recurrence per year, or those with an EORTC recurrence score of ≥5. All patients will be followed up at our outpatient clinic and the pathology results will be reviewed. Routine second-look TURBT will be arranged within 2-6 weeks after the first operation should there be any indications as stated in the EAU guidelines. For patients in the intermediate or high-risk groups, 1-year of intravesical BCG therapy will be offered. Surveillance flexible cystoscopy will be performed at a 3-month interval until 2 years after the index surgery, and then every 6 months for another 3 years. Biopsy will be taken and TURBT will be offered if there is any suspicious tumour recurrence noted during surveillance cystoscopy.Primary outcome is recurrence-free survival at 2 years.

Interventions

• Procedure Conventional Transurethral Resection of Bladder Tumour
  Conventional TURBT is performed by resecting the bladder tumour in a piecemeal manner with a top-down approach. The bladder tumour specimen is fragmented during the procedure and whether a complete resection has been achieved is determined by the operating surgeon's judgment intra-operatively.
• Procedure Transurethral En Bloc Resection of Bladder Tumour
  This surgical technique resects the bladder tumour underneath the submucosal plane, and the bladder tumour can be removed in one piece.

Primary outcome measures

• Rate of recurrence-free survival [Time frame: At Year 2]

Secondary outcome measures (7)

• Rate of progression-free survival [Time frame: At Year 2]
• Cancer-specific survival [Time frame: At Year 2]
• Overall survival [Time frame: At Year 2]
• Adverse Events [Time frame: On Day 30 after operation]
• Detrusor muscle sampling rate [Time frame: On Day 30 after operation]
• Day of hospital stay [Time frame: On Day 30 after operation]
• Total operation time [Time frame: On Day 30 after operation]

Eligibility criteria

Inclusion criteria

• Age 18 years or above
• Fulfil any one of the following three criteria:

• Recurrent bladder tumour
• Multiple bladder tumours
• Any bladder tumour size of >1cm

Exclusion criteria

• EAU low-risk NIMBC as intravesical BCG therapy should not be offered (5)
• EAU very high-risk NMIBC as upfront radical cystectomy should be offered (5)
• Any prior use of intravesical BCG therapy
• Presence or prior history of upper urinary tract malignancy
• Presence of clinically significant cardiovascular disease (History of acute myocardial infarction, presence of uncontrolled angina within 3 months before screening, New York Heart Association Class III or IV congestive heart failure, presence of ventricular arrhythmias, or presence of second-degree or third-degree heart block) (16)
• Presence of GOLD Stage III or IV chronic obstructive pulmonary disease
• ECOG performance status ≥ 2 (Ambulatory and capable of all self-care but unable to carry our any work activities) (18)
• History of bleeding disorder or use of anti-coagulants
• Pregnancy
• Presence of other active malignancy

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Hong Kong · 2 centers

• Prince of Wales Hospital — Hong Kong
• North District Hospital — Sheung Shui

Publications

• Teoh JY, D'Andrea D, Gallioli A, Yanagisawa T, MacLennan S, Nicoletti R, Fai NC, Maffei D, Hurle R, Lusuardi L, Malavaud B, Miki J, Kramer M, Mostafid H, Enikeev D, Babjuk M, Breda A, Shariat S, Gontero P, Herrmann T. En bloc resection of bladder tumour: the rebirth of past through reminiscence. World J Urol. 2023 Oct;41(10):2599-2606. doi: 10.1007/s00345-023-04547-0. Epub 2023 Aug 16. PMID 37584691
• Teoh JY, Cheng CH, Tsang CF, Kai-Man Li J, Kwun-Chung Cheng B, Hoi-Chak Chan W, Kwun-Wai Chan W, Churk-Fai Li T, Chiu Y, Law MC, Lok-Hei Leung C, Sze-Ho Ho B, Yue-Kit Lee C, Cheong-Kin Chan R, Shu-Yin Chan E, Chan MT, Hok-Leung Tsu J, Tam HM, Lam KM, So HS, Cho CL, Ng CM, Chan CK, Liu PL, Wing-Hong Chu R, Tsui-Lin Ng A, Chu SK, Yee CH, Yiu MK, Lo KL, Au WH, Ma WK, Ka-Fung Chiu P, Sze-Wan Kwok H, Y PMID 38692956
• Teoh JY, Huang J, Ko WY, Lok V, Choi P, Ng CF, Sengupta S, Mostafid H, Kamat AM, Black PC, Shariat S, Babjuk M, Wong MC. Global Trends of Bladder Cancer Incidence and Mortality, and Their Associations with Tobacco Use and Gross Domestic Product Per Capita. Eur Urol. 2020 Dec;78(6):893-906. doi: 10.1016/j.eururo.2020.09.006. Epub 2020 Sep 21. PMID 32972792
• Yun EJ, Meng MV, Carroll PR. Evaluation of the patient with hematuria. Med Clin North Am. 2004 Mar;88(2):329-43. doi: 10.1016/S0025-7125(03)00172-X. PMID 15049581
• Gontero P, Birtle A, Capoun O, Comperat E, Dominguez-Escrig JL, Liedberg F, Mariappan P, Masson-Lecomte A, Mostafid HA, Pradere B, Rai BP, van Rhijn BWG, Seisen T, Shariat SF, Soria F, Soukup V, Wood R, Xylinas EN. European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ)-A Summary of the 2024 Guidelines Update. Eur Urol. 2024 Dec;86(6):531-549. PMID 39155194

Identifiers

NCT: NCT07724886 · CRE 2025.055

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗