COBRA

Chemoablation Or Bladder Resection with Adjuvant Chemotherapy in recurrent Non-Muscle Invasive Bladder Cancer

Title:
COBRA NMIBC

Aim:
To assess if the efficacy of a dose-dense chemoablation with Mitomycin C (MMC) with adjuvant Bacillus Calmette–Guérin (BCG) in non-responding patients is superior regarding long-term effect compared to standard treatment with transurethral resection of bladder tumour (TURBT) and adjuvant intravesical instillation therapy in patients with recurrent Ta low-grade (LG) tumours.

Number of patients:
We expect to include 272 patients from 9 sites in the Nordic countries.

Methods:
The study will be conducted as an international multicentre randomised, controlled trial (RCT), where included participants are randomized between the intervention and control group. This trial design has been chosen to ensure the highest level of evidence (RCT). The international multicentre approach has been selected to ensure the highest degree of applicability of the results across countries and centres as previous studies have not had an international approach. The randomisation will be conducted 1:1.

Patient enrolment is expected to be ongoing for approximately 2 years in the following two arms:

Control group: Patients will have TURBT or outpatient biopsy and tumour fulguration performed, followed by standard intravesical instillation therapy according to tumour histology.
Intervention group: Patients will undergo dose dense chemoablation with MMC three times per week for two weeks followed by adjuvant MMC or TURBT and adjuvant BCG according to response.

Both groups follow the standard follow-up regimen according to European and national guidelines. Tumours with intermediate risk of recurrence are followed with a cystoscopy after three months, then once after nine months, then yearly for a minimum of 5 years if no recurrence. Tumours with high risk of recurrence are followed with cystoscopy and urine cytology every three months for two years, followed by cystoscopies twice a year until recurrence free for five years and then yearly.

End points are two-year recurrence-free survival (RFS), five-year RFS, and number of procedures (TURBTs or tumour fulguration) between groups.

Inclusion/exclusion criteria:
Inclusion criteria:

Tumour recurrence after previous urothelial tumour of Ta low-grade
Tumours smaller than 2 cm in diameter

Exclusion criteria:

Known history of invasive tumour of the bladder (T1+)
Known history of CIS of the bladder
Previous MMC or BCG-treatment except for single instillations following previous TURBTs
Solid tumour with suspicions of invasion
Tumour in the bladder neck or urethra
Suspicion of CIS (positive cytology with high-grade neoplastic cells combined with suspicious flat lesions seen at cystoscopy)
Small bladder volume (less than 100 ml) or incontinence
Prior radiation therapy to the pelvic area, as radiation affects the bladder function and instillation therapy is a suboptimal treatment for this patient group