CUA 2017: A Propensity Score Analysis of Radical Cystectomy vs. Bladder-Sparing Trimodal Therapy in the Setting of a Multidisciplinary Bladder Cancer Clinic

Toronto, Ontario ( Muscle-invasive bladder cancer (MIBC) drives the mortality of bladder cancer as a disease, and until now, the only level 1 evidence for its management supports the use of neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). However, NAC + RC is a highly morbid intervention, particularly in the elderly population that entails the bladder cancer patient pool.

While trimodal therapy (TMT), a combination of maximal resection with TURBT, chemotherapy and radiation therapy, has been described and is often accepted for elderly patients who cannot tolerate RC, it has never been assessed as a potentially equal option for healthy eligible patients.

In this study, the multidisciplinary team at the University of Toronto presents data on a retrospectively reviewed prospectively collected database of patients treated for MIBC with either TMT or standard of care (RC with NAC if eligible) between 2008 and 2013. Patients in the TMT arm underwent NAC, maximal local resection, and then chemoradiation therapy. They were followed prospectively in our multidisciplinary bladder tumor clinic. Primary outcomes were disease-specific survival (DSS) and overall survival (OS). 

112 patients with MIBC were included after matching (56 treated with TMT and 56 by RC). Median age was 68.0 years and 29.5% were cT3/cT4. 

At a median follow-up of 4.51 years, there were 20 (35.7%) deaths (13 from BC) in the RC group and 22 (39.3%) deaths (13 from BC) in the TMT group. Five-year DSS was 73.2% and 76.6%, in the RC and TMT groups, respectively (p=0.49). Salvage cystectomy was performed in 6/56 TMT patients (10.7%).

In this matched cohort, the results of TMT appear to be non-inferior to standard of care. While the authors accept that the patients are a selected population of patients with MIBC (generally focal disease, no significant hydronephrosis, etc), considering the significant morbidity associated with RC, shouldn’t a less invasive option be seriously considered even in a select population?

In a recent publication, Seisen and colleagues1 assessed the outcomes of TMT and standard of care using a large United States cancer database (National Cancer Database [NCDB]) and found that TMT was inferior to RC. However, despite the attention it received, Kulkarni and Klaassen2 point out the significant flaws in such an analysis – specifically, the intent of treatment, patient selection, and rigor of treatment in a population level analysis is insufficient to truly assess TMT. Particularly since TMT in the United States, outside of academic centers, was usually reserved for elderly patients unable to receive RC. As NCDB only assessed overall survival, cancer-specific outcomes could not be assessed.

Further work needs to be completed prospectively to truly answer this question. Even if it is only non-inferior in a selected population, that population would benefit from a less invasive treatment option.

Presented By: Girish S. Kulkarni, MD, PhD, FRCPC, University Health Network, Toronto

Co-Authors: Thomas Hermanns, Yanliang Wei, Bimal Bhindi, Raj Satkunasivam, Paul Athanasopoulos, Peter J Bostrom, Cynthia Kuk, Kathy Li, Arnoud J Templeton, Srikala S Sridhar, Theodorus H van der Kwast, Peter Chung, Robert Bristow, Michael Milosevic, Padraig Warde, Neil E. Fleshner, Michael A. Jewett, Shaheena Bashir, Alexandre Zlotta
Institution: University Health Network, Toronto, ON, Canada

Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto   Twitter: @tchandra_uromd at the  72nd Canadian Urological Association Annual Meeting - June 24 - 27, 2017 - Toronto, Ontario, Canada

1. Comparative Effectiveness of Trimodal Therapy Versus Radical Cystectomy for Localized Muscle-invasive Urothelial Carcinoma of the Bladder. Seisen T, Sun M, Lipsitz SR, Abdollah F, Leow JJ, Menon M, Preston MA, Harshman LC, Kibel AS, Nguyen PL, Bellmunt J, Choueiri TK, Trinh QD. Eur Urol. 2017 Apr 12. pii: S0302-2838(17)30266-X. doi: 10.1016/j.eururo.2017.03.038. [Epub ahead of print]

2. Kulkarni GS, Klaassen Z. Trimodal therapy is inferior to radical cystectomy for muscle-invasive bladder cancer using population-level data: is there evidence in the (lack of) details? Eur Urol. In press.