Real-world outcomes for high-risk non-muscle-invasive bladder cancer: screened patients for the BRAVO trial

Abstract

Objective: To report real-world outcomes for high-risk non-muscle-invasive bladder cancer (HRNMIBC), including bacillus Calmette-Guérin (BCG) and radical cystectomy (RC), as randomised comparisons of these have not been possible.

Methods: We detail consecutive participants screened for the BRAVO randomised controlled trial comparing RC with BCG (International Standard Randomised Controlled Trial Number [ISRCTN]12509361). Patients were prospectively registered and case-note review used for outcomes. The primary outcome was overall survival. Secondary outcomes included recurrence, progression, metastasis, and bladder cancer-specific survival.

Results and limitations: A total of 193 patients were screened, including 106 (54.9%) who received BCG, 43 (22.3%) primary RC, 37 (19.2%) 'other' treatment and seven (3.6%) hyperthermic intravesical mitomycin C. All-cause death occurred in 55 (28.5%) patients at median (interquartile range [IQR]) of 29.0 (19.5-42.0) months. In multivariable analysis, overall mortality was more common in older patients (hazard ratio [HR] 2.63, 95% confidence interval [CI] 1.35-5.13; Cox P = 0.004 for age >70 years), those recruited from district hospitals (HR 0.53, 95% CI 0.3-0.95; P = 0.032) and those who did not undergo RC as their first treatment (HR 2.16, 95% CI 1.17-3.99; P = 0.014). In all, 17 (8.8%) patients died from bladder cancer (BC) at median (IQR) of 22.5 (19-36.25) months. In multivariable analysis, BC-specific mortality was more common in older patients (HR 4.87, 95% CI 1.1-21.6; P = 0.037) and those with Tis/T1 disease (HR 2.26, 95% CI 1.23-4.16; P = 0.008) but did not vary with initial treatment.

Conclusions: Patients with HRNMIBC are at high-risk of mortality. Those choosing RC as their initial treatment have lower risks of mortality than others, although this may reflect fitness and selection.

Keywords: BCG; High‐risk non‐muscle‐invasive bladder cancer; RCT; bladder cancer; feasibility study; radical cystectomy; real‐world data; surgical trial.

Fig. 1

Patient flow in BRAVO screened cohort. The CONSORT diagram details first and subsequent treatment, as well as progression, metastases, and deaths per group. *Two patients progressed from low‐grade to high‐grade (HG) tumours.

Fig. 2

Survival outcomes stratified by initial treatment received. Kaplan–Meier survival analysis detailing (a) local recurrence in patients receiving bladder‐sparing treatments (including BCG and HIVEC, (b) progression to more advanced disease for bladder‐sparing treatments, (c) MFS, (d) Bladder CSS, (e) OS, and (f) OS for patients receiving primary or treatment‐failure RC. Univariable Cox regression (two‐sided) P values are shown.