BACKGROUND: Bacillus Calmette-Guerin (BCG) is the recommended therapy for high and intermediate risk non-muscle invasive bladder cancer (NMIBC), but treatment failure is common. While a radical cystectomy is recommended after BCG failure, some patients desire bladder preservation and others are poor surgical candidates. Salvage chemotherapy treatments may be offered to this subgroup of patients. OBJECTIVE: To assess if combination, hyperthermic Gemcitabine and Docetaxel chemotherapy (GEM/DOCE) is a safe and effective salvage option for treating NMIBC. METHODS: Sixty patients who received our GEM/DOCE protocol between 2007-2017 were identified (51 BCG failures, 9 BCG naïve). This study measured overall treatment success, defined as no recurrence, progression, cystectomy, nor death due to bladder cancer. Kaplan-Meier curves were used to ascertain probability of treatment success. The log-rank test was used to identify factors associated with treatment success. RESULTS: Sixty patients received treatment with a median follow-up of 14.9 months. All patients completed the induction course with no significant adverse effects. Overall treatment success was 83% at first surveillance, 69% at 1 year, and 55% at 2 years in the entire cohort, and 90% at first surveillance, 74% at 1 year, and 56% at 2 years in the BCG-failure patients. All-cause and bladder-cancer-specific survival were both 97.9% at 1 year, 85.9% and 94.6% respectively at 2 years. Three patients underwent cystectomy at a median of 10.2 months, two of these were secondary to recurrences. Three patients had progression of their disease. CONCLUSIONS: Hyperthermic GEM/DOCE seems to be a well-tolerated salvage regimen that demonstrates a reasonable efficacy and warrants further investigation.

Introduction To evaluate the response of patients with high-risk bacillus Calmette-Guerin (BCG)–unresponsive non-muscle invasive bladder cancer (NMIBC) who we treated with intravesical CG0070, a conditionally replicating granulocyte macrophage colony-stimulating factor (GM-CSF) containing an RB promoter. Methods 15 patients with residual high grade BCG-unresponsive CIS +/- Ta/T1/T2 bladder cancer received one or more 6-week instillations of intravesical CG0070 and were retrospectively reviewed. Overall response including the number, location, grade and stage of recurrences, were recorded. Side effects of intravesical instillation of CG0070 were also investigated. 11 of the 15 patients had at least 2.5 years of follow up both before and after treatment, permitting statistical chi-square analysis for the 2.5 year pre- and post-CG0070 periods. Results Of the 15 patients, 5 had Ta + Cis, 4 had T1 + CIS, 4 had CIS alone, and 2 had T2 + CIS prior to CG0070 instillation. Complete response of CIS was seen in 60% at 6 months, 47% at 12 months, and 40% at 24 months. Overall, 40% of patients remained tumor free and none progressed. For the 11 patients amenable to statistical analysis, 32 recurrences were noted within 2.5 years before therapy and 13 2.5 years after (p <0.01). 40% of patients experienced no adverse events as a result of treatment. Most common side effects were hematuria (33.3%), malaise/fatigue (33.3%), and urgency/frequency (26.7%). Discussion Treatment with intravesical CG0070 for high-risk BCG-unresponsive bladder cancer appears to be a promising salvage regimen worthy of further investigation.