ASCO GU 2018: Comparative Effectiveness of Bladder-preserving Tri-modality Therapy Versus Radical Cystectomy for Muscle-invasive Bladder Cancer

San Francisco, CA ( 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 only recently been assessed as a potentially equal option for healthy eligible patients.1

In a recent publication, Seisen and colleagues2 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 Klaassen3 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.

In this study, the authors approach the question from a theoretical standpoint. They developed a Markov decision analysis model comparing the effectiveness of TMT and RC with the primary endpoint of quality-adjusted life years (QALYs).

They simulated the lifetime outcomes for 67-year-old patients after definitive treatment for AJCC Stage cT2-T4aN0M0 MIBC using two strategies: TMT or RC +/- neoadjuvant chemotherapy (NAC). They utilized probabilities of success extracted from the literature, including the studies listed above for TMT, to determine the incremental effectiveness in QALYs.

Interestingly, TMT was the most effective strategy with an incremental gain of 1.13 QALYs over RC (8.37 versus 7.24 QALYs, respectively). One-way sensitivity analyses demonstrated the model was most sensitive to the quality of life (QoL) parameters (i.e. the utilities) for RC and TMT - TMT was more effective than RC irrespective of the RC utility! This is somewhat intuitive, as bladder sparing obviously would provide better QoL outcomes.

The model was relatively less sensitive to the probability of death for either strategy. Probabilistic sensitivity analysis demonstrated that TMT was more effective than RC for 75% of model iterations. This can be understood, as long-term cancer outcomes of TMT are still wanting, compared to RC for which there is significant literature.

They conclude, from this Markov model, that treatment of MIBC with organ-sparing TMT in appropriately-selected patients may result in a gain of over 1 QALY relative to RC. Further prospective investigation into the QoL implications of these treatment modalities is warranted. More importantly, more oncologic data is still needed to establish TMT as an equal option for appropriately selected patients.

Speaker: Trevor Royce

Co-Authors: Alan D. Smith, Nazanin Fallah-Rad, Aaron Richard Hansen

Institution(s): Princess Margaret Hospital, Toronto, ON, Canada

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA

1. Kulkarni GS, Hermanns T, Wei Y, et al. Propensity score analysis of radical cystectomy versus bladder-sparing trimodal therapy in the setting of a multidisciplinary bladder cancer clinic. J Clin Oncol 2017 [Epub ahead of print].

2. 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]

3. 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.