Disease progression among patients who receive available bladder preservation therapies after failure of BCG therapy in the SEER-Medicare data

453 Background: For patients with high-grade (HG) non-muscle invasive bladder cancer (NMIBC) who recur after Bacillus Calmette-Guérin (BCG) therapy, treatment options other than radical cystectomy have been limited. This study examined real-world utilization and outcomes of current bladder preservation therapies (BPT) after BCG treatment. Methods: We analyzed the SEER-Medicare database and identified patients diagnosed with HG NMIBC between 2008 and 2015 who received at least one BCG induction course (defined as ≥5 weekly instillations). Use of BPT within six months of the last consecutive BCG instillation was identified and included BCG + interferon alpha, docetaxel, doxorubicin, epirubicin, gemcitabine, mitomycin C, nab-paclitaxel, thiotepa, valrubicin, or their combinations. Progression was identified as initiation of treatment for muscle-invasive bladder cancer, radical cystectomy, or presence of metastases. Time to progression (TTP) was defined as time from BPT initiation to progression event. Progression-free survival (PFS) was assessed from BPT initiation and defined as the absence of progression or death due to bladder cancer. TTP and PFS were assessed using Kaplan-Meier analysis. Results: A total of 7,074 patients were diagnosed with HG NMIBC and received ≥ 5 BCG weekly induction instillations. Of these, 8.8% (620 patients) initiated BPT. The most commonly used agents were mitomycin C (66.0%), followed by BCG + interferon alpha (22.9%), valrubicin (4.0%), doxorubicin (2.9%), and gemcitabine (2.1%). Disease progression occurred in 18.7% of patients within 1 year of treatment initiation (40.5% due to metastases), 36.4% within 3 years (50.0% due to metastases), and 45.4% within 5 years (50.2% due to metastases). The rate of PFS was 80.9%, 61.8%, and 52.3% at 1, 3, and 5 years, respectively. Conclusions: High rates of metastatic disease are noted in HG NMIBC following available BPT treatments after failure of BCG therapy. A high unmet need remains for novel bladder-sparing therapies to improve outcomes in this difficult-to-treat population.