Introduction:
After the recurrence of NMIBC following initial BCG therapy, risk stratified management taking into account failure categorization, tumor characteristics, and patient factors includes radical cystectomy, clinical trial enrollment, and off-label use of intravesical chemotherapy. Many patients, however, remain unfit for or unwilling to have major extirpative surgery and thus identification of efficacious and safe alternatives to radical cystectomy is of paramount importance. Building on promising, single center data, we report the findings of a large, multi-institutional cohort of patients receiving intravesical Gemcitabine and Docetaxol after BCG failure for the first time.
Methods:
IRB approval and data transfer agreements were established at each participating institution. Participating institutions retrospectively reviewed all patients treated with an induction course of sequential intravesical Gem/Doce for NMIBC between June 2009 and May 2018. De-identified data was maintained using REDCap software, supported by University of Iowa NIH/CTSA program grant 2UL1TR000442-06 Maintenance therapy was continued based on individual institutional protocols. Surveillance for recurrence was carried out per AUA guidelines. Recurrence and survival probabilities were plotted using the Kaplan-Meier methods and Cox regression models were used to evaluate the effect of patient, disease, and treatment variables on outcomes. Only patients with recurrent NMIBC and a history of prior BCG treatment were included in the analysis.
Results:
Two hundred and seventy-six patients with a median follow-up of 22.9 months and a median number of 2 prior intravesical therapy induction courses were identified and included in the analysis. Only 3.3% of patients were unable to tolerate the full induction course of therapy. High grade recurrence free survival was 65% at 1 year and 52% at 2 years. Progression free survival was 97% and 93% at 1 and 2 years, respectively. On Cox regression analysis, clinical stage, number of prior BCG failures, BCG failure categorization, and treating institution did not impact disease recurrence. The addition of maintenance therapy was significantly associated with recurrence free survival (HR 2.37, 95% CI 1.36-4.11, p<0.01). Sixteen percent of patients underwent cystectomy at a median of 11.3 month from starting therapy. Bladder cancer specific mortality was 1% at 1 year and 5% at 2 years. There was no difference in outcome between patients with CIS and those with no CIS.
Conclusion:
In this large, multi-institutional review of a heavily pretreated patient population with moderate duration follow-up, the intravesical administration of Gemcitabine and Docetaxol is safe, well tolerated, and appears efficacious in preventing recurrence without compromising progression free or cancer specific survival in patients with recurrent, NMIBC after BCG failure. It is notable that BCG failure number and categoary, clinical T stage, and the presence of CIS did not impact treatment success while the administration of maintenance therapy significantly improved recurrence free survivial. In this era of BCG shortage and personalized medicine, prospective and mechanistic research is warranted.
Funding: Work supported by the John & Carol Walter Family Foundation
SOS – A MULTI-INSTITUTIONAL EVALUATION OF RESCUES THERAPY WITH INTRAVESICAL GEMCITABINE AND DOCETAXOL FOR NON-MUSCLE INVASIVE BLADDER CANCER AFTER BCG FAILURE
Category
Bladder Cancer > Non-Muscle Invasive Bladder Cancer
Description
Poster #22 / Podium #
Poster Session I
12/4/2019
2:00 PM - 5:30 PM
Presented By: Nathan Brooks
Authors:
Nathan Brooks
Ryan Steinberg
Lewis Thomas
Sarah Mott
Andrew Vitale
Trafford Crump
Marcus Daniels
Jonathan Wang
Supriya Nagaraju
William DeWolf
Donald Lamm
Max Kates
Eric Hyndman
Ashish Kamat
Trinity Bivalacqua
Kenneth Nepple
Michael O'Donnell