Contemporary outcomes in non-muscle-invasive bladder cancer: a large European multicentre study

Abstract

Objective: To report real-world rates of non-muscle-invasive bladder cancer (NMIBC) recurrence and progression within a European multicentre cohort with detailed information on intravesical instillation courses, as contemporary data on oncological outcomes in NMIBC are limited.

Patients and methods: A total of 1918 patients with NMIBC treated with transurethral resection of bladder tumour (TURBT) were retrospectively identified from six tertiary-referral European centres (2015-2022). Patients were stratified according to European Association of Urology 2021 criteria into low- (LR), intermediate- (IR), high- (HR) and very high-risk (VHR) categories. Cumulative incidence plots and multivariable competing risks regression models addressing 5-year rates of high-grade (HG) recurrence and progression were fitted. Sensitivity analyses focused on patients receiving intravesical instillations and tested for the effect of adequate course (Bacillus Calmette-Guérin: five or more induction + two or more maintenance instillations; mitomycin C: complete induction + ≥11 maintenance instillations).

Results: Of all NMIBC patients identified, 467 (24.3%) were LR vs 582 (30.3%) IR vs 739 (38.5%) HR vs 130 (6.8%) VHR. The median (interquartile range) follow-up after TURBT was 26 (12-46) months. The 5-year HG recurrence rates were 7.2% in LR vs 17.3% in IR vs 26.7% in HR vs 30.9% in VHR patients, resulting in a three-, five- and seven-fold higher risk of IR, HR and VHR, respectively, relative to LR (all P < 0.001). The 5-year progression rates were 3.9% in LR vs 5.2% in IR vs 13.6% in HR vs 31.6% in VHR patients, resulting in a six- and nine-fold higher risk for HR and VHR, respectively, relative to LR (all P < 0.001). In all, 1001 (52.2%) patients underwent intravesical instillations. Those receiving adequate instillation course (244/1001 [24.3%]) had lower HG-recurrence (hazard ratio 0.3, P < 0.001) and progression (hazard ratio 0.2, P = 0.001) risk.

Conclusions: Patients with HR/VHR NMIBC face significantly higher HG recurrence and progression risks. While tailored treatment strategies are needed, adherence to adequate instillation course remains crucial for optimising oncological outcomes.

Keywords: BCG; bladder cancer; intravesical instillations; non‐muscle‐invasive; oncological outcomes; progression; recurrence.

Fig. 1

Patient selection flowchart according to the CONSORT guidelines.

Fig. 2

Cumulative incidence curves depicting HG recurrence (A) and progression (B) according to the EAU 2021 risk categories of the 1918 patients with NMIBC from six European tertiary referral centres treated with TURBT between 2015 and 2022.

Fig. 3

Cox‐derived LOESS‐smoothed hazard ratio for HG recurrence (A) and progression (B) according to number of instillations. The solid line represents the smoothed hazard ratio, while the shaded area indicates the 95% CI. The dashed horizontal line at hazard ratio = 1 represents the threshold where the risk is neither increased nor decreased.