AUA 2020: Multi-Institutional Outcomes of Patients with High-Risk Non-Muscle Invasive Bladder Cancer Who Undergo Radical Cystectomy After BCG and Subsequent Salvage Intravesical Therapy

( There are multiple ongoing salvage intravesical therapy trials for patients with non-muscle invasive bladder cancer who do not respond to Bacillus Calmette-Guérin (BCG). However, oncologic outcomes for patients who fail salvage intravesical therapy are not well established. At the American Urological Association (AUA) 2020 Virtual Meeting, Vignesh Packiam, MD, and colleagues presented results of their evaluation of the impact of salvage intravesical therapy on survival in patients with non-muscle invasive bladder cancer previously treated with BCG who ultimately underwent radical cystectomy. 

This study included a retrospective review of two institutional radical cystectomy registries to identify patients with non-muscle invasive bladder cancer who received at least one complete induction course of BCG and subsequently underwent radical cystectomy for bladder cancer between 2000-2018. Patients were stratified by receipt of salvage intravesical therapy following BCG prior to radical cystectomy. Oncologic outcomes were compared using Cox proportional hazards regression analysis and the Kaplan-Meier method. For sensitivity analysis, patients with salvage intravesical therapy were matched 1:3 by presenting tumor stage to patients without salvage intravesical therapy. 

There were a total of 371 patients who underwent radical cystectomy after receiving BCG, of whom 55 (15%) received salvage intravesical therapy, most commonly mitomycin C (n=26), valrubicin (n=8), gemcitabine (n=7), and CG0070 (n=6):

salvage intravesical therapy

The median follow-up among survivors was 1.1 (IQR 0-4.3) years, during which time 149 patients died, including 79 from bladder cancer. Age, race, body mass index (BMI), and Charlson Comorbidity Index were similar between groups. Patients who received salvage intravesical therapy were more likely to initially present with carcinoma in situ (CIS) (27% vs 17%) and less likely to present with T1 disease (33% versus 50%, both p<0.05). Receipt of salvage intravesical therapy was not associated with increased risk of adverse pathology (≥pT2 or pN+) at radical cystectomy (33% versus 41%, p=0.27).

Furthermore, on Kaplan-Meier analysis, receipt of salvage intravesical therapy was not associated with cancer-specific or overall survival. On multivariable Cox proportional hazards regression analysis, clinical-stage prior to radical cystectomy (CIS vs Ta hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.01-3.32; T1 vs Ta/CIS HR 3.12, 95% CI 1.37-7.13; T2 vs Ta/CIS HR 6.92, 95% CI 3.22-14.9), but not receipt of salvage intravesical therapy (HR 1.07, 95% CI 0.55-2.04), was associated with inferior cancer-specific survival. On matched analysis, salvage intravesical therapy remained without association with survival outcomes. 

Dr. Packiam concluded his presentation with the following take-home messages:

  • These results suggest that radical cystectomy following salvage intravesical therapy after BCG is not associated with inferior oncologic outcomes
  • While careful management should continue to be used in this setting, these data can improve counseling for patients considering salvage intravesical therapy trials

Presented by: Vignesh T. Packiam, MD, Urologic Oncology Fellow, Mayo Clinic, Rochester, Minnesota

Co-Authors: Craig V. Labbate, Stephen A. Boorjian, Robert F. Tarrell, Brittany Adamic, Mohammad Mahmoud, Matvey Tsivian, Svetlana Avulova, John C. Cheville, R. Jeffrey Karnes, Matthew K. Tollefson, Ryan P. Werntz, Gary D. Steinberg, Igor Frank

Written by: Zachary Klaassen, MD, MSc, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Augusta, Georgia, Twitter: @zklaassen_md at the 2020 American Urological Association (AUA) Annual Meeting, Virtual Experience #AUA20, June 27- 28, 2020

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