Introduction: In recent years, more patients are selecting to forgo radical cystectomy (RC) and select bladder sparing treatment (BST) for Bacillus Calmette-Guerin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC). Herein, we assessed long-term survival outcomes of BCG unresponsive NMIBC patients treated with BST versus early RC. Methods: We performed an IRB approved retrospective study analyzing patients with BCG unresponsive NMIBC diagnosed between April 2001 and September 2021 at our institution. Survival outcomes between the following patient cohorts were compared: 1) Early RC versus BST and 2) Early RC versus delayed RC. Primary endpoint was overall-(OS) and cancer-specific survival (CSS). Cox-regression was used to estimate OS, CSS, high-grade recurrence-free survival (RFS) and progression-free survival (PFS) endpoints. Results: A total 118 patients who met criteria for BCG unresponsive disease were identified (80 BST versus 38 early RC). Patients undergoing early RC were more likely to have higher T1 stage (52.6% vs 35.0%, p=0.048) and lymphovascular invasion (10.5% vs 0%, p=0.003) compared to those treated with BST. Comparative outcomes for OS (HR: 1.34, 95% CI: 0.65-2.76, log-rank p=0.429) and CSS (HR: 0.84, 95% CI: 0.21-3.38, log-rank p=0.803) between early RC and BST were not significant (inconclusive). With a median follow-up of 72.1 months (IQR: 30.1-134.0), at 60 months, BST treated patients had a high-grade RFS rate of: 37%, PFS to muscle-invasive disease/metastasis rate: 84% and avoidance of RC rate: 81%. The risk of high-grade recurrence was higher in current smokers (HR: 6.00, 95% CI: 1.73-20.6, p=0.005). For patients undergoing RC for BCG unresponsive disease, median time to RC were 2.1 months and 15.8 months for early and delayed RC respectively. Comparative outcomes were similar for the early and delayed RC: OS (58% vs 54%) (HR: 1.17, 95% CI: 0.50-2.71, p=0.717) and CSS (81% vs 81%) (HR: 1.07, 95% CI: 0.23-4.92, log-rank p=0.927). Conclusions: Long-term survival outcomes following BST (with delayed RC when indicated) in patients with BCG unresponsive NMIBC is not inferior compared to early RC. SOURCE OF Funding: This research was supported by the Wayne B. Duddlesten Professorship in Cancer Research, the Raymond and Maria Floyd Bladder Cancer Research Foundation Grant, NIH/NCI UTMD Anderson SPORE in Genitourinary Cancer (P50CA091846) and the Cancer Center Support Grant (NCI Grant P30 CA016672)
