Oncological Outcomes of Sequential Intravesical Gemcitabine and Docetaxel in Patients with Non-Muscle Invasive Bladder Cancer

Background: Bacillus Calmette-Guerin (BCG) unresponsive/relapsing patients with non-muscle invasive bladder cancer (NMIBC) who prefer bladder preservation over radical cystectomy (RC) or those who do not qualify for surgery may be offered intravesical therapies. Gemcitabine (GEM) combined with Docetaxel (DOCE) has been offered at Johns Hopkins Hospital (JHH). Objective: To evaluate experience with GEM/DOCE, to confirm safety of the regimen, to identify populations that may benefit most, and to consider the appropriate endpoints for judging efficacy of second line therapies. Methods: Thirty-three patients who received full induction GEM/DOCE since 2011, per the protocol adapted from U. Iowa, were identified and characterized. Multivariable logistic regression was used to determine factors associated with recurrence. Cox proportional hazard models evaluated risk factors for disease-free survival (DFS) and high-grade recurrence-free survival (HG-RFS). Results: There were no serious adverse effects of therapy. Across all patients, median follow-up time was 18.6 months with a median DFS of 6.5 months, 42% 1-year, and 24% 2-year DFS. Median HG-RFS was 17.1 months with 56% 1-year and 42% 2-year HG-RFS. Among patients initially presenting with HG-NMIBC, 46% (13/28) had HG recurrence. BCG unresponsive/relapsing patients (N=25) displayed 49% 1-year HG-RFS and 34% 2-year HG-RFS. In total, there were 5 LG and 16 HG recurrences, with 5 progressions and 8 cystectomies among these. Conclusions: GEM/DOCE is a well-tolerated therapy that deserves further study as an alternative to immediate RC for highly selected patients with HG-NMIBC. BCG naive patients responded more effectively than BCG unresponsive/relapsing patients. As anticipated, GEM/DOCE efficacy was improved for HG only patients.