BRAVO Study: Surgery vs. Immunotherapy – Which treatment is best in bladder cancer?

Not Applicable

Completed

• Conditions: Bladder cancer; Specialty: Cancer, Primary sub-specialty: Bladder; UKCRC code/ Disease: Cancer/ Malignant neoplasms of urinary tract; Cancer

• Registration Number: ISRCTN12509361
• Lead Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust

Brief Summary

2017 Protocol article in https://pubmed.ncbi.nlm.nih.gov/28801444/ protocol (added 27/11/2020) 2021 Results article in https://pubmed.ncbi.nlm.nih.gov/33332191/ results (added 17/08/2021)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-09-06
• Study Completion: 2018-09-30
• Last Update Posted: 3 October 2022

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Inclusion criteria as of 23/03/2017:
1. Male or female aged = 18 years old.
2. Patients with a new diagnosis of high-risk (high grade or grade 3) non-muscle invasive urothelial carcinoma (staged as either pTa, pTis or pT1). Patients with previous low grade NMIBC are suitable.
3. The tumour is either solely urothelial cell carcinoma or has urothelial cell carcinoma as the majority histological component.
4. In addition to the HRNMIBC bladder tumour, there needs to be one or more risk factor from:
4.1. Presence of pTis in the bladder
4.2. Presence of pTis in the prostatic urethra
4.3. Lymphovascular invasion
4.4. Vascular invasion
4.5. Residual Grade 3/High grade UCC on re-resection (or initial TURBT if no re-resection)
4.6. Multifocal disease (>3 tumours at initial resection)
4.7. Young age (<65 years old)
4.8. Initial tumour Size > 3cm (or >5g in histology specimen)
4.9. pT1 stage
5. Either re-resection of the bladder (following the initial diagnostic TURBT) within 3 months prior to randomisation confirming the absence of muscle invasion
OR
5.1. The initial diagnostic TURBT biopsy contains muscle, AND
5.2. The radiological and pathological stage assessment are in agreement regarding stage and absence of muscle invasion, AND
5.3. A re-resection is not appropriate in the opinion of the treating clinician AND
5.4. The initial TURBT is within 3 months prior to randomisation
6. CT or cross sectional imaging of the abdomen and pelvis within the year prior to starting treatment.
7. Imaging of the lungs and thorax within 3 months prior to randomisation.
8. Suitable and fit for both mBCG and RC as determined by the treating clinician
9. Central MDT pathological review agrees diagnosis
10. If female, must be (as documented in patient notes):
10.1. Postmenopausal (no menses for 12 months without an alternative medical cause), or
10.2. Surgically sterile (hysterectomy, bilateral salpingectomy or bilateral oophorectomy), or
10.3. Using acceptable contraception2 (which must be continued for 7 days after the last dose of BCG or until RC is carried out). Women of child bearing potential must undergo a pregnancy test before randomisation.
10.4. Not breast feeding

Original inclusion criteria:
1. Male or female aged = 18 years old
2. Patients with a new diagnosis of high-risk (high grade or grade 3) non-muscle invasive urothelial carcinoma (staged as either pTis, pTa or pT1). Patients with previous low grade NMIBC are suitable
3. The tumour is either solely urothelial cell carcinoma or has urothelial cell carcinoma as the majority histological component
4. In addition to the HRNMIBC bladder tumour, there needs to be one or more risk factor from:
4.1. Presence of pTis in the bladder
4.2. Presence of pTis in the prostatic urethra
4.3. Lymphovascular invasion
4.4. Vascular invasion
4.5. Residual Grade 3/High grade UCC on re-resection

Exclusion Criteria

1. Solely non-urothelial or variant urothelial pathology
2. Unable or not willing to give informed consent
3. Previous high risk (high grade or grade 3) NMI or invasive bladder cancer
4. Any previous treatment with intravesical BCG
5. Any other malignancy (excluding non-melanomatous skin cancer, low-risk prostate cancer and prior low risk bladder cancer)

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1. Eligibility rate is reportedas the number of patients screened for entry to the study and considered eligible within the 18 month recruitment period2. Recruitment rate is reported as the number of eligible patients randomised within the 18 month recruitment period