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Background: Guidelines recommend neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). Current recommendations do not consider genomic profiles, although the Basal/Squamous (Ba/Sq) subtype is less likely to respond to NAC compared to Urothelial-like (Uro) and Genomically Unstable (GU) subtypes. The aim of this study is to perform cost-effectiveness analyses of a de-escalated use of NAC in patients with Ba/Sq tumors and MIBC.

Methods: A cost-effectiveness analysis was performed using a decision analytic Markov model using a healthcare provider perspective. Treatment and prognosis probabilities originated from the Bladder Cancer Data Base, Sweden (BladderBaSe) 2.0. Information on molecular subtype and outcomes was retrieved from published studies, and quality-adjusted life year (QALY) data were obtained from the iROC trial. Costs were collected from the regional healthcare registers in Sweden, utility values were obtained from the literature, and outcomes are presented as incremental cost-effectiveness ratio (ICER). Scenario analyses, along with several one-way and probabilistic sensitivity analyses were performed to capture uncertainties.

Results: At a 5-year time horizon, the model predicts that molecular subtype-based treatment has an ICER of 4,964 Euro/QALY (66,766 Swedish Krona/QALY), which is deemed cost-effective in the Swedish setting. At €7,427 (100,000 SEK) willingness-to-pay threshold, the molecular subtype-based treatment has a 65% probability of being cost-effective. The results were not sensitive to uncertainty analyses.

Conclusion: Molecular subtype-based treatment of MIBC, i.e., refraining from administering NAC to patients with Ba/Sq tumors, is cost-effective compared to the current treatment practices in Sweden.