The Value Of A Comprehensive Primary Outcome - Results Of A Negative Randomized Control Trial In The Non-Muscle Invasive Bladder Cancer Population

Introduction: American Urological Association (AUA) guidelines recommend intravesical chemotherapy to be givenfollowing transurethral resection ofa bladder tumor. Prior studies have shown the benefit of mitomycin as well as gemcitabine. However, no study has compared the two agents.Materials and methods: The study was designed as an open label 1:1:1 randomized controlled trial, comparing intravesical mitomycin, gemcitabine and saline as a single intraoperative instillation immediately following transurethral resection of suspected bladder tumor. Primary endpoint was any grade 3 events according to NCI CTCAE Version 4.03, this captures any return trip to the operating room for recurrence of cancer or other event (benign bladder/urethra). Secondary endpoints were progression free survival for urothelial cell carcinoma and adverse events.Results: A total of 82 patients were enrolled and randomized, unfortunately the trial was suspended early due to protocol deviations. In an intention to treat analysis, freedom from grade > 3 events at 2 years was 74.8% in the no treatment arm, 51.0% in the mitomycin arm, and 56.0% in the gemcitabine arm (p = 0.81). Freedom from cancer recurrence for all patients was 62.3%. In the no treatment arm, it was 78.8%, and 50.7% and 63.6% in the mitomycin arm and gemcitabine arm respectively (p = 0.28). In a univariate analysis, the only patient variable significantly associated with the primary outcome was pathologic T stage (p < 0.002).Conclusion: This study provides an example of a novel, patient centered primary outcome with the goal of determining which treatment paradigms provide the greatest oncologic and clinic benefit.