Molecular Subtyping to Stratify Treatment of Muscle-Invasive Bladder Cancer: A Cost Effective Analysis

For patients with muscle-invasive bladder cancer (MIBC), current “gold standard” treatment is radical cystectomy with the addition of neoadjuvant chemotherapy (NAC), which has been shown to improve survival compared with surgery alone. However, as noted by Diana Magee, MD, MPH, from the Division of Urology, Department of Surgery, University of Toronto, Canada, despite the proven benefits of NAC in MIBC, concerns about delay of surgery, the potential toxicity of therapy, and, more important, the inability to predict response and hence identify who will benefit, have limited its use. She pointed out that Identifying the subset of patients who are more likely respond to NAC would be helpful in the treatment of MIBC patients and presented the results of a study showing that a precision medicine strategy based on molecular subtyping to stratify treatment of MIBC can favorably affect survival and quality of life and can be cost-effective in these patients.1 Bladder cancer is the most expensive cancer diagnosis and the annual cost of MIBC treatment is four-fold higher than that of non-MIBC.2

To help better identify patients who are more likely to be NAC responders, Dr Magee and colleagues at the University of Toronto and Fox Chase Cancer Center, Philadelphia, conducted a study to determine whether a precision medicine treatment strategy based on molecular subtyping of MIBC would yield greater efficacy and be more cost-effective than standard approaches of cystectomy plus undirected NAC. They also calculated the maximum cost at which molecular subtyping would be deemed cost effective from the healthcare payer perspective. The study was funded by the Canadian Urologic Oncology Group.

The investigators created a 2D Markov microsimulation model to evaluate the management of MIBC using TreeAge Pro 2019 (TreeAge Software, Inc). The Markov model simulates patients over time and allows for changes in health state with disease progression. Three strategies were applied in the primary analysis: NAC at current usage rates (36%), universal use of NAC, and molecular subtype-driven use of NAC. The classification of subtyping proposed by Seiler et al3 was used to create the model using a commercially available test. The model involved three inputs: probabilities, based on a systematic search of the bladder cancer literature; relevant utilities for urologic phases of care, obtained by completing a search of the Canadian Agency for Drugs and Technologies in Health (CADTH); and costs, mostly obtained from a retrospective chart review of over 4000 patients who underwent radical cystectomy or trimodal therapy at the University Health Network (UHN), a tertiary cancer-specific care center in Toronto, between 2008 and 2012. The base case for the model was an adult patient with MIBC stage cT2-4N0M0 eligible for NAC and radical cystectomy.

The results for the three modeled arms demonstrated that subtype-directed care yielded greater efficacy in terms of quality-adjusted life-years (QALYs) (9.14) vs current NAC or universal NAC usage (8.34 or 8.73, respectively). Costs were similar for current NAC and subtype-directed care ($62,478 and $62,579, respectively) but higher for universal NAC ($76,962). Overall survival rates at 1, 3, 5, and 10 years were all slightly higher on the subtype-directed care arm compared with the other two arms. The incremental cost-effectiveness ratio for subtype care compared with current NAC usage rates was Can$127 per QALY. This fell far below the willingness-to-pay (WTP) threshold of Can$50,000, Dr Magee explained. This meant that the maximum cost at which subtyping would be cost-effective was Can$40,000.

Thus, Dr Magee and her colleagues concluded that MIBC patients treated with NAC based on a subtype driven approach can result in improved survival, greater QALYs and be cost-effective within a single payer healthcare system (such as exists in Canada). Although a push toward the universal use of NAC will result in improved survival compared with current rates of use, this is likely not the best approach, Dr Magee commented. She noted that since their model was based on the literature available at the time and before widespread clinical implementation, it will require prospective validation.


  1. Magee DE, Cheung DC, Sander B, et al. Molecular subtyping to stratify the treatment of muscle- invasive bladder cancer: a cost-effectiveness analysis. Poster #47 presented at the 22nd Annual Meeting of the Society of Urologic Oncology (SUO), December 1-3, 2021, Orlando, FL.
  2. Cooksley CD, Avritscher EB, Grossman HB, et al. Clinical model of cost of bladder cancer in the elderly. Urology. 2008;71(3):519-525. DOI: 10.1016/j.urology.2007.10.056
  3. Seiler R, Ashab HAD, Erho N, et al. Impact of molecular subtypes in muscle-invasive bladder cancer on predicting response and survival after neoadjuvant chemotherapy. Eur Urol. 2017;72(4):544-554. DOI: 10.1016/j.eururo.2017.03.030