Continuous saline bladder irrigation for two hours following transurethral resection of bladder tumors in patients with non-muscle invasive bladder cancer does not prevent recurrence or progression compared with intravesical Mitomycin-C

Andrew T Lenis,Nicholas M Donin,Kian Asanad,Karim Chamie,Maher Blaibel

doi:10.1186/s12894-018-0408-6

Abstract

BackgroundIntravesical Mitomycin-C (MMC) following transurethral resection of bladder tumor (TURBT), while efficacious, is associated with side effects and poor utilization. Continuous saline bladder irrigation (CSBI) has been examined as an alternative. In this study we sought to compare the rates of recurrence and/or progression in patients with NMIBC who were treated with either MMC or CSBI after TURBT.MethodsWe retrospectively reviewed records of patients with NMIBC at our institution in 2012–2015. Perioperative use of MMC (40 mg in 20 mL), CSBI (two hours), or neither were recorded. Primary outcome was time to recurrence or progression. Descriptive statistics, chi-squared analysis, Kaplan-Meier survival analysis, and Cox multivariable regression analyses were performed.Results205 patients met inclusion criteria. Forty-five (22.0%) patients received CSBI, 71 (34.6%) received MMC, and 89 (43.4%) received no perioperative therapy. On survival analysis, MMC was associated with improved DFS compared with CSBI (p = 0.001) and no treatment (p = 0.0009). On multivariable analysis, high risk disease was associated with increased risk of recurrence or progression (HR 2.77, 95% CI: 1.28–6.01), whereas adjuvant therapy (HR 0.35, 95% CI: 0.20–0.59) and MMC (HR 0.43, 95% CI: 0.25–0.75) were associated with decreased risk.ConclusionsPostoperative MMC was associated with improved DFS compared with CSBI and no treatment. The DFS benefit seen with CSBI in other studies may be limited to patients receiving prolonged irrigation. New intravesical agents being evaluated may consider saline as a control given our data demonstrating that short-term CSBI is not superior to TURBT alone.

Highlights

Intravesical Mitomycin-C (MMC) following transurethral resection of bladder tumor (TURBT), while efficacious, is associated with side effects and poor utilization
The standard adjuvant therapy following transurethral resection of bladder tumor (TURBT) for Non-muscle invasive bladder cancer (NMIBC) is intravesical instillation of Mitomycin-C (MMC), which has been shown to decrease rates of recurrence by approximately 11%, this is variable depending on the number of and time from prior recurrences. [4, 5] The posited mechanism of action is to prevent free-floating tumor cells in the urine following TURBT from re-implanting onto the bladder wall
Strategies to reduce the risk of recurrence and progression, including intravesical chemotherapy and immunotherapy, have been shown to be effective. [4, 12] none of these are without risk of potential significant side effects

Summary

Introduction

Intravesical Mitomycin-C (MMC) following transurethral resection of bladder tumor (TURBT), while efficacious, is associated with side effects and poor utilization. The standard adjuvant therapy following transurethral resection of bladder tumor (TURBT) for NMIBC is intravesical instillation of Mitomycin-C (MMC), which has been shown to decrease rates of recurrence by approximately 11%, this is variable depending on the number of and time from prior recurrences. [6] MMC is contraindicated when there is a concern for bladder perforation and when there is significant post-operative gross hematuria Considering these limitations, there is an urgent need for alternative strategies to prevent the re-implantation of tumor cells following TURBT, to reduce recurrence and minimize the morbidity of the disease. [9, 10] In our current study, we sought to evaluate continuous bladder irrigation with isotonic (0.9% NaCl) normal saline (CBSI) for two hours following TURBT as a strategy to reduce recurrence or progression in patients with NMIBC A 2012 Cochrane review of intravesical gemcitabine yielded conflicting results. [7] Apaziquone is a novel intravesical alkylating agent that has demonstrated safety and tolerability in patients as a post-TURBT instillation and is being evaluated in Phase 3 clinical trials (NCT02563561). [8] Alternatively, several groups have utilized sterile water and saline irrigation over 18–24 h as a strategy to lyse floating tumors cells and prevent the re-implantation of cells into the bladder wall. [9, 10] In our current study, we sought to evaluate continuous bladder irrigation with isotonic (0.9% NaCl) normal saline (CBSI) for two hours following TURBT as a strategy to reduce recurrence or progression in patients with NMIBC

Methods

Results

Discussion

Conclusion