Comparative Effectiveness of Bladder-preserving Trimodality Therapy Versus Radical Cystectomy for Muscle-invasive Bladder Cancer
Key findings
- Using a Markov model, trimodality therapy (TMT) for muscle-invasive bladder cancer (MIBC) was associated with a gain in effectiveness of 0.59 in quality-adjusted life years (QALYs) compared with radical cystectomy (RC)
- Sensitivity analysis demonstrated that the gain in QALYs with TMT was driven largely by the differences between TMT and RC in quality of life
- Life years were identical with TMT and RC, and survival rates were very similar
- Multidisciplinary teams should consider TMT for appropriately selected patients with MIBC
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For a definitive treatment of muscle-invasive bladder cancer (MIBC), professional societies accept both radical cystectomy (RC) and the newer organ-preserving approach known as trimodality therapy (TMT), which is the transurethral resection of the bladder tumor, chemotherapy and radiation. Historically, radical cystectomy has been considered the gold standard treatment for MIBC. However, for properly selected patients, both approaches have been shown to be near-equivalent in terms of survival outcomes.
Massachusetts General Hospital researchers Adam S. Feldman, MD, MPH, director of Urology Research, Jason A. Efstathiou, MD, DPhil, director of Genitourinary Service in the Department of Radiation Oncology, and colleagues used computerized decision-analytic modeling to compare the efficacy of TMT with RC. Their findings, published in Clinical Genitourinary Cancer, show that quality of life in MIBC patients may be better with TMT than with RC.
The Computer Model
To conduct their study, researchers used a Markov model, which is often used in medicine to simulate how a disease changes over time in hypothetical patients. Transitions between health states (e.g., from newly diagnosed cancer to complete response, or from advanced disease to death) are assumed to occur in yearly cycles.
Patients entered the computer model at age 67 and terminated at death or age 100. The initial treatment was TMT, or RC with or without neoadjuvant chemotherapy. Patients in the TMT group could have complete response. If they didn't, they had the option for immediate salvage RC. If patients with complete response had disease recurrence later, they had an option for delayed salvage RC.
Data on variables such as recurrence rates, death rates and quality of life were plugged into the model from existing medical literature or from experiences with TMT at Mass General. The primary endpoint was quality-adjusted life years (QALYs), a measure of survival adjusted for quality of life.
All MIBC Patients
The first run of the model included patients with localized urothelial cell MIBC, stage T2–T4aN0M0 (meaning there is no evidence of primary tumor and no regional metastases detected). Unadjusted expected life years were identical with the two strategies: 8.89 life years for both TMT and RC. The 5-, 10- and 15-year survival rates were very similar: 51%, 31% and 24% for TMT versus 50%, 34% and 26% for RC.
Regarding the primary endpoint, the adjusted expected values were 7.83 QALYs for TMT and 7.24 for RC, a gain of 0.59 QALYs in favor of TMT.
In the second run of the model, the researchers used RC data derived from a patient cohort treated at MD Anderson Cancer Center between 2000 and 2010. Patients underwent RC only if they had T2 disease without hydroureteronephrosis, lymphovascular invasion or micropapillary disease.
Under these assumptions, the model predicted 7.83 QALYs for TMT and 7.76 for RC, marking a gain of 0.07 QALYs in favor of TMT.
Contemporary Cohort
Finally, the researchers limited the TMT strategy to patients from a more contemporary cohort: those treated at Mass General between 2005 and 2013. The model predicted 9.37 QALYs for TMT and 7.76 for RC in the low-risk cohort, a gain of 1.61 QALYs in favor of TMT.
Sensitivity Analysis
According to one-way sensitivity analysis, the gain in QALYs with TMT was driven largely by the differences between TMT and RC in quality of life. Probabilistic sensitivity analysis demonstrated that TMT was more effective than RC during 63% of model iterations.
TMT May Be Preferable to RC for Appropriate Candidates
Even though survival seems similar with the two strategies, TMT offers a preferable alternative approach to definitive management of MIBC because, for select patients, it may be superior to RC in terms of quality of life. This may be particularly true for patients who have comorbidities that make RC less advisable. Thus, members of the multidisciplinary team are encouraged to consider TMT for MIBC patients for whom the approach is deemed appropriate.
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