OBJECTIVES : Standard treatment options are limited for patients with high-grade (HG) non-muscle invasive bladder cancer (NMIBC) after adequate Bacillus Calmette-Guérin (BCG) therapy. We examined the real-world treatment patterns and survival among BCG unresponsive patients diagnosed with HG NMIBC in the US.

METHODS : Using SEER-Medicare database (2008-2015), we identified BCG unresponsive patients among those who received adequate BCG (≥7 instillations within 9 months of diagnosis) based on the initiation of additional therapy within 12 months of the last consecutive BCG instillation. Therapies evaluated post BCG were radical cystectomy and bladder-preserving treatments (BPTs) (thiotepa, valrubicin, gemcitabine, mitomycin C, docetaxel, nab-paclitaxel, any combinations of these, chemo-radiation, and BCG + interferon alpha). Overall survival (OS) and bladder cancer-specific survival (BCSS) were assessed using Kaplan-Meier analysis and Cox proportional hazards models.

RESULTS : Among the 16,837 patients with HG NMIBC, only 13.9% received adequate BCG. Of these, 16.2% (378 patients) were BCG unresponsive and formed the study sample. Only 15.1% of these patients received radical cystectomy as their first treatment post-BCG. Of the 84.9% undergoing BPT, the most commonly used agents were mitomycin C (55.1%), BCG + interferon alpha (17.8%), valrubicin (11.8%), and gemcitabine (7.5%). The 5-year OS was similar between the two groups (52.6% vs. 51.6%) but patients receiving radical cystectomy had a lower 5-year BCSS (67.4% vs. 79.6%). After adjusting for potential confounders, patients receiving radical cystectomy had a significantly higher hazard of bladder cancer mortality (HR 2.09; 95% CI 1.05-4.13).

CONCLUSIONS : BCG was underutilized in patients with HG NMIBC, indicating substantial unmet needs. The proportion of patients receiving radical cystectomy among BCG unresponsive patients was also low. Patients who received BPTs had similar OS as those who underwent radical cystectomy, but had a lower risk of bladder-cancer specific mortality. Further research is warranted to inform the contemporary treatment patterns and outcomes of this difficult-to-treat patient population.