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497 Background: Due to ongoing bacillus Calmette-Guerin (BCG) shortages, sequential intravesical gemcitabine and docetaxel (Gem/Doce) has been increasingly utilized as first-line adjuvant treatment for patients with high-risk non-muscle invasive bladder cancer. Herein, we compared oncologic outcomes and tolerance of Gem/Doce versus BCG. Methods: We retrospectively identified 312 patients with high-risk, treatment-naïve, NMIBC treated at our institution between January 2011 and December 2021; 174 treated with BCG and 138 treated with Gem/Doce. After complete TURBT, patients received a 6 weekly intravesical induction regimen of Gem/Doce or BCG, followed by maintenance if disease free at first follow-up. The primary outcome was high-grade (HG) recurrence-free survival (RFS). Cox multivariable regression analyses were performed. Adverse events were reported using CTCAE v5. Results: Median follow-up for patients receiving Gem/Doce and BCG was 23 and 49 months, respectively. Baseline clinicopathologic characteristics were similar between groups, including presence of CIS (41% vs 44%, p=0.6) and T1 (37% vs 41%, p=0.5) disease for patients receiving Gem/Doce and BCG, respectively. HG-RFS estimates at 6, 12, and 24-months were 92%, 85%, and 81% for Gem/Doce and 76%, 71%, and 69% for BCG, respectively. On multivariable Cox regression analyses controlling for age, gender, treatment year, and presence of CIS, Gem/Doce treatment was associated with superior HG-RFS (HR 0.57, p=0.04) and RFS (HR 0.56, p=0.02) versus BCG (Table). Progression-free, cystectomy-free, cancer-specific, and overall survival were similar between groups. Induction BCG was associated with greater treatment discontinuation (9.2% vs 2.9%, p=0.02), dysuria (p=0.03), and arthralgias (p=0.02), but less bladder spasms (p

497 Background: Bacillus Calmette-Guerin (BCG) is currently recommended as adjuvant therapy following complete transurethral resection of bladder tumor (TURBT) for high-risk non-muscle invasive bladder cancer (NMIBC). However, continued BCG production shortages have precluded the use of BCG in many urologic practices. Efficacy of sequential intravesical gemcitabine and docetaxel (Gem/Doce) in the BCG failure setting has been reproduced across multiple institutions. In response to the continuing BCG shortage, Gem/Doce has been utilized at our institution in the BCG-naïve setting. We report the outcomes of a large cohort of patients with high-risk BCG-naïve NMIBC treated with Gem/Doce. Methods: We retrospectively identified all patients with BCG-naïve high-risk NMIBC who were treated with Gem/Doce from May 2013 through April 2021. We included patients with intent to receive 6 weekly intravesical instillations of sequential 1 gram gemcitabine and 37.5mg docetaxel after complete TURBT. Monthly maintenance of 2 years was initiated if disease free at first follow-up. The primary outcome was recurrence-free survival (RFS) and efficacy was evaluated in an intention-to-treat manner. Recurrence was defined as pathologically confirmed tumor relapse in the bladder or prostatic urethra. Progression was defined as T-stage increase from Ta or CIS to T1 or development of muscle invasive or metastatic disease. Survival was assessed using the Kaplan-Meier method and log rank test, indexed from the first Gem/Doce instillation. Results: One hundred seven patients with median follow-up of 15 months were included in the analysis. There were 47 with any CIS, 55 with T1 disease, and 7 with micropapillary variant histology. Four patients did not complete a full induction cycle due to hematuria (3) and severe frequency/nocturia (1). 19 patients sustained a recurrence at any point during follow-up. RFS was 89%, 85%, and 82% at 6, 12, and 24 months, respectively. No difference in RFS was seen in patients with or without CIS (p = 0.42). No patients met criteria for either form of disease progression. One patient underwent cystectomy due to end-stage lower urinary tract symptoms, with final pathology pTisN0. No patients died of bladder cancer. Overall survival was 84% at 24 months. 46 patients reported any symptoms during treatment. Common side effects included urinary frequency/urgency (36%), hematuria (11%), and dysuria (8%). Conclusions: In a large cohort of high-risk, BCG-naïve NMIBC patients, Gem/Doce showed excellent efficacy (84% 2-year HG-RFS). These rates are similar to modern treatment naïve cohorts receiving BCG. Prospective comparative analysis of Gem/Doce in BCG-naïve populations is warranted.[Table: see text]

496 Background: Intravesical gemcitabine-docetaxel (Gem/Doce) has emerged as an efficacious and well-tolerated therapy for NMIBC. At first cytoscopic evaluation, success rate for BCG failures is 75-80% with 60% of responders remaining disease free at 24 months. Success rates are even higher for BCG naïve patients with close to 90% disease free at 3 months, and 93% of responders HG disease free at 24 months. There is an unmet need for effective bladder-sparing regimens for Gem/Doce failures. FDA-approved agents in this setting have poor long-term efficacy; Valrubicin has an 8% 24-month disease free rate, and recently approved Pembrolizumab has less than 20% complete response at 1 year. Based on poor efficacy of alternatives, we evaluated sequential intravesical valrubicin-docetaxel (Val/Doce) as a rescue therapy for NMIBC. Methods: We retrospectively identified all patients with NMIBC who were treated with Val/Doce between April 2013 and June 2021. Patients were included with intent to receive 6 weekly intravesical instillations of sequential 800 mg valrubicin and 37.5 mg docetaxel after complete TURBT. Monthly maintenance of 2 years was initiated if disease free at 3-month cytoscopic evaluation. The primary outcome was recurrence-free survival (RFS). Progression events included the development of muscle invasive or metastatic disease as well as any cystectomy. Survival was assessed using the Kaplan-Meier method and log rank test, indexed from start of Val/Doce induction. Surveillance was performed according to AUA guidelines. Results: The final cohort included 75 patients with median follow-up of 21 months. Of these patients, 12 were treated with Val/Doce for low-grade Ta disease, with 60% disease free at 2 years and no subsequent HG occurrences. The remaining 63 patients had high-grade disease of which 86% were BCG failures and 89% were Gem/Doce unresponsive. The 2 year RFS for high-grade patients was 39%. CIS was present in 56% of the cohort. RFS was similar for those with and without CIS. Progression occurred in 12 of the patients with high-grade disease. Of note, 10 underwent cystectomy and 2 died of metastatic bladder cancer, yielding a bladder cancer specific death rate of 3%. Overall and cystectomy-free survival was 88 and 85% at 24 months, respectively. The most commonly reported side effects were bladder spasms (24%), urinary frequency (13%), and dysuria (11%). There were 3 patients who could not tolerant a full induction course. Conclusions: Sequential intravesical valrubicin-docetaxel will rescue a substantial portion of patients with HG NMIBC failing Gem/Doce or BCG. Thus, the regimen allows a high proportion of patients ( > 80%) to retain their bladders with an acceptable ( < 20%) progression rate without succumbing to bladder cancer-related death ( < 5%).[Table: see text]

573 Background: Intravesical bacillus Calmette-Guérin (BCG) is the first-line treatment for high-risk non-muscle invasive bladder cancer (NMIBC). Unfortunately, disease recurrence/progression is common and associated with increased risk of death from bladder cancer. While radical cystectomy remains the preferred treatment for BCG unresponsive NMIBC, many patients are either unwilling or unfit to undergo surgery. Previous retrospective studies have demonstrated the efficacy of intravesical gemcitabine and docetaxel (Gem/Doce) for treating NMIBC after BCG failure. However, the long-term outcomes of this cohort are unknown. We report 5-year survival outcomes of patients treated with intravesical Gem/Doce after BCG failure. Methods: We retrospectively identified patients at our institution who were treated with Gem/Doce for high-risk NMIBC after BCG failure between 2009 and 2017. Patients received six weekly intravesical Gem/Doce instillations. Initial responders received monthly maintenance instillations for 2 years. Surveillance was performed according to American Urological Association guidelines. Survival time was measured from start of Gem/Doce induction. Outcomes included high-grade recurrence-free survival (HG-RFS), progression-free survival (PFS), cystectomy-free survival (CFS), cancer-specific survival (CSS) and overall survival (OS). Recurrence was defined as pathologically confirmed tumor relapse in the bladder or prostatic urethra. Progression was defined as recurrence of disease with stage T2 or greater, cystectomy or death due to bladder cancer. Survival probabilities were calculated with the Kaplan-Meier method. Results: A total of 97 patients with a median age of 73 years were treated with Gem/Doce after BCG failure. Median follow-up was 49 months. BCG failure was further stratified as BCG unresponsive (35%), BCG relapsing (38%), BCG intolerant (11%) or unspecified (16%). 71% and 21% of patients had carcinoma in-situ and high-grade T1 disease, respectively. Complete response at initial surveillance was 74% and median duration of response was 26 months. Overall HG-RFS at 1, 2 and 5 years was 60%, 51% and 31%, respectively. HG-RFS was similar among BCG unresponsive patients and the overall cohort (see table). During follow-up, 18 patients (19%) underwent radical cystectomy and 28 patients (29%) experienced disease progression. PFS, CFS, CSS and OS at 5 years was 68%, 75%, 91% and 64%, respectively. Conclusions: Intravesical Gem/Doce for high-risk NMIBC after BCG failure offers long-term efficacy and substantial durability of response with a high likelihood of bladder preservation at five years after induction. Future prospective trials assessing Gem/Doce are warranted.[Table: see text]

469 Background: Bacillus Calmette-Guerin (BCG) is the standard of care for patients with new non-muscle invasive bladder cancer (NMIBC) after transurethral tumor resection. While BCG has been compared to single agent intravesical chemotherapy as first-line therapy, few studies exist comparing BCG to sequential intravesical chemotherapy regimens. The objective of this work was to determine the efficacy of sequential intravesical gemcitabine and docetaxel (Gem/Doce) in BCG naïve patients with NMIBC. Methods: Patients without prior BCG exposure who underwent Gem/Doce intravesical treatments were retrospectively identified. These patients had been treated with 6 weekly instillations of gemcitabine (1 gram of gemcitabine in 50 ml of sterile water) followed immediately by docetaxel (37.5 mg of docetaxel in 50 mL of saline). Patients without recurrence then underwent maintenance therapy with monthly instillations for two years. Treatment success was defined as no bladder cancer recurrence and no cystectomy. Survival analysis was performed using the Kaplan Meier method. Results: 30 patients were treated with a median follow-up of 18 months. Eighty percent (n=24) of patients had high risk disease. Median age was 78 years old. The most common indications for Gem/Doce therapy were “advanced age/frailty” (n=15), “immunosuppression” (n=4), and “BCG Shortage” (n=4). Treatment success was 96% at 3 months, 89% at 1 year, and 89% at 2 years. No patients progressed or required cystectomy. Treatments were generally well tolerated, with only one patient unable to finish induction and two patients declining maintenance. Side-effects included urinary urgency/frequency (30%), dysuria (26%), and hematuria (23%). A need for dose reduction or delay was uncommon (16%). The all-cause mortality rate was 3.5% at 1 year, and 16.5% at 2 years. Neither bladder cancer nor the treatments were the cause of any of the deaths. Conclusions: Sequential intravesical gemcitabine and docetaxel is an effective treatment for BCG naïve NIMBC. Treatments are generally well tolerated even in a frail and comorbid patient population. Further evaluation of this combination therapy for BCG naïve disease is warranted.