As reported in the Journal of Clinical Oncology by Catto et al, the BRAVO-Feasibility study showed that recruitment of patients with high-grade, non–muscle invasive bladder cancer into a randomized trial comparing radical cystectomy vs intravesical bacillus Calmette-Guérin (BCG) proved difficult, suggesting the unlikelihood of comparing these treatments in a large-scale trial.
As stated by the investigators, “High-grade, non–muscle invasive bladder cancer is a heterogeneous disease. Treatments include intravesical maintenance BCG (mBCG) and radical cystectomy. We wanted to understand whether a randomized trial comparing these options was possible…Although mBCG avoids bladder removal, it leaves patients at risk of [disease] progression and may affect health-related quality of life through local symptoms and anxiety. [Radical cystectomy] removes the risk of local disease progression, but may be overtreatment for nonprogressing tumors.”
“A randomized controlled trial comparing mBCG and radical cystectomy will be challenging to recruit into. Around 10% of patients with high-risk, high-grade, non–muscle invasive bladder cancer have a lethal disease and may be better treated by primary radical treatment. Conversely, many are suitable for bladder preservation and may maintain their prediagnosis quality of life.”— Catto et al
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Study Details
The study, carried out in seven National Health Service cancer networks in the United Kingdom, involved screening and recruitment of patients with newly diagnosed, high-risk, high-grade, non–muscle invasive bladder cancer suitable for both treatments. Recruitment was limited to an 18-month period. The primary outcome was the number of patients screened, deemed eligible, recruited, and randomly assigned.
Key Findings
A total of 407 patients were screened; 215 (52.8%) were found to be eligible between October 2016 and March 2018.
The most common reasons for ineligibility were prior high-grade, non–muscle invasive bladder cancer or BCG; non–muscle invasive bladder cancer lacking additional risk factors; other malignancy; or unsuitability of patients for both treatments.
Investigators approached 185 of the 215 eligible patients, with 51 (27.6%) agreeing to be randomly assigned in the trial. Reasons for not agreeing to random assignment included:
- Preference for mBCG for 77 patients (50.0%)
- Preference for radical cystectomy for 39 (25.3%)
- Dislike of random assignment for 27 (17.5%)
- Concerns about study participation for 8 (5.2%).
Of the 51 patients, 1 did not proceed to random assignment, with a total of 50 being randomly assigned to mBCG (n = 25) or radical cystectomy (n = 25).
In the mBCG group, 23 patients (92.0%) received mBCG, 4 had non–muscle invasive bladder cancer after induction, 3 had non–muscle invasive bladder cancer at 4 months, and 4 underwent radical cystectomy. At study closure, two patients had metastatic bladder cancer.
In the radical cystectomy group, 20 patients underwent cystectomy, including 5 (25.0%) with no tumor; 13 (65.0%) with high-grade, non–muscle invasive bladder cancer; and 2 (10.0%) with specimens showing muscle invasion. At follow-up, all patients were free of disease.
Adverse events of any grade occurred in 15 (65.2%) of 23 patients in the BCG group who received mBCG and in 13 (65.0%) of 20 in the radical cystectomy group who underwent cystectomy. Most adverse events were mild in severity.
Quality of life was generally similar in both groups at 12 months. In the EORTC QLQ-C30 functional domains, the radical cystectomy group exhibited a reduction in quality of life at 3 months with a return to baseline levels between 6 and 12 months, whereas little change was observed in the mBCG group over 12 months. Both groups exhibited few changes in QLQ-C30 symptom scores over 12 months.
The investigators concluded, “A randomized controlled trial comparing mBCG and radical cystectomy will be challenging to recruit into. Around 10% of patients with high-risk, high-grade, non–muscle invasive bladder cancer have a lethal disease and may be better treated by primary radical treatment. Conversely, many are suitable for bladder preservation and may maintain their prediagnosis quality of life.”
James W.F. Catto, MBChB, PhD, of The Medical School, The University of Sheffield, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
