Patients who recur with carcinoma in situ (CIS) at the time of bacillus Calmette-Guerin (BCG) unresponsive diagnosis in non-muscle invasive bladder cancer (NMIBC) experience worse outcomes than those with pure papillary urothelial carcinoma (pUC). However, in this population of BCG unresponsive NMIBC patients, it is unknown whether oncologic outcomes are divergent for those with pure CIS versus those with both concomitant CIS and pUC. The present study aims to elucidate this unknown, particularly as it relates to disease progression. A retrospective review of BCG treated patients at Moffitt Cancer Center between 2012 and 2018 was performed. BCG unresponsive disease was identified according to the 2018 US Food and Drug Administration (FDA) definition. Clinical and pathologic data, including recurrent tumor staging at the time of BCG unresponsive diagnosis and disease progression in the form of muscle invasive disease or metastasis, was captured. Cohort descriptive statistics were analyzed using Pearson's chi square for categorical variables and Wilcoxon rank-sum for continuous variables. Progression-free survival (PFS) was estimated using Kaplan-Meier (KM) analysis and compared using the log-rank test. Cox regression was used to control for covariates pertaining to patient demographics, tumor characteristics, and future treatment. 126 individuals were defined as BCG unresponsive. The cohort was predominantly male (81.7%), median age was 71.0 (64.0-77.0), and the median follow-up from unresponsive diagnosis was 33.0 months (16.0-57.8) (Table 1). Patients were stratified by presence of CIS into 3 groups – pure CIS, concomitant CIS + Ta/T1 pUC, and pUC alone. Those with concomitant CIS experienced worse PFS than those with pure pUC or pure CIS disease (p=0.03; Figure 1). This finding was corroborated by multivariate cox regression analysis where the presence of concomitant CIS independently predicted worse PFS (hazard ratio [HR]: 4.22, 95% confidence interval [CI]: 1.35-13.19, p=0.01). Notably, separate analysis revealed no significant difference;in PFS between patients with CIS + T1;disease and those with CIS + Ta disease (HR: 1.76, CI: 0.37-8.33, p=0.5). The worse outcomes traditionally seen with BCG unresponsive patients who have CIS compared to those with pUC alone seems to be driven by patients with concomitant CIS and pUC; those patients with BCG unresponsive pure CIS and pure pUC have similar rates of progression. Larger patient cohorts are required to validate this finding and determine its potential value in shaping clinical trial design and treatment guidelines for BCG unresponsive NMIBC patients. [ABSTRACT FROM AUTHOR]