Real-world outcomes of bladder-sparing strategies for BCG-unresponsive non-muscle-invasive bladder cancer: a multicenter study.

INTRODUCTION

Patients with BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC) face a high risk of disease progression. While radical cystectomy (RC) remains the recommended standard of care, many patients are unfit for or unwilling to undergo radical surgery, leading to bladder-sparing strategies spreading in real-world practice. This study aims to describe the oncological outcomes of patients diagnosed with BCG-unresponsive NMIBC treated with gemcitabine/docetaxel (Gem/Doce), electromotive drug administration of mitomycin C (EMDA/MMC), further BCG, or upfront RC.

METHODS

We included patients diagnosed with BCG-unresponsive NMIBC treated across 21 European centers (2009–2024) with either intravesical Gem/Doce, EMDA/MMC, further BCG, or upfront RC. Cumulative incidence curves were used to estimate the risk of recurrence, high-grade recurrence, progression, cancer-specific and overall mortality. Multivariable Cox regression models were used to assess the association between treatment type and the risk of recurrence and progression.

RESULTS

Of the 361 patients, 104 (28%) received Gem/Doce, 58 (16%) EMDA/MMC, 150 (42%) further BCG, and 49 (14%) underwent RC. Overall median follow-up was 73 months. Recurrence and high-grade recurrence rates were comparable between Gem/Doce and EMDA/MMC (adjusted HR: 1.30 and 0.40, respectively; both p > 0.5). The 2-year risk of progression was 15% with Gem/Doce, 20% with EMDA/MMC, and 30% with further BCG (p < 0.001). In multivariable analysis, Gem/Doce was associated with a significantly lower risk of progression compared to further BCG (adjusted HR: 0.19, 95% CI 0.09–0.43; p < 0.001). The 2-year cancer-specific mortality was 0% for both Gem/Doce and EMDA/MMC, 4% for BCG, and 7% for RC, with corresponding other-cause mortality rates of 3%, 8%, 11%, and 8%, respectively.

CONCLUSIONS

In real-world practice, our study indicates that both Gem/Doce and EMDA/MMC represent viable treatment bladder-sparing options for patients with BCG-unresponsive NMIBC who refuse or are unfit for RC. For patients eligible and consenting to surgery, RC remains the guideline-endorsed standard. Prospective trials are warranted to define the optimal therapeutic algorithm for this challenging patient population.