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. 2025 Jun 2;8(6):e2517056.
doi: 10.1001/jamanetworkopen.2025.17056.

Cost-Effectiveness of Trimodal Therapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer

Daniel D Joyce  1 , Kevin M Wymer  2 , John A Graves  3 , Stephen A Boorjian  2 , John L Gore  4 , Ali Raza Khaki  5 , Ann C Raldow  6 , Stephen B Williams  7 , Angela B Smith  8   9 , Vidit Sharma  2
Affiliations

Cost-Effectiveness of Trimodal Therapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer

Daniel D Joyce et al. JAMA Netw Open. .

Abstract

Importance: Trimodal therapy (TMT) is included as an alternative to radical cystectomy (RC) for definitive management of muscle-invasive bladder cancer (MIBC) in current clinical guidelines. Moreover, a 2023 retrospective analysis reported similar oncologic outcomes between these treatments among patients deemed fit for RC. Data regarding the comparative value of these treatments are lacking.

Objective: To evaluate the comparative cost-effectiveness of TMT and RC for treatment of MIBC.

Design, setting, and participants: This economic evaluation compared cost-effectiveness of treatments using a health transition state microsimulation model of patients with bladder cancer treated between 2005 and 2017 with 5- and 10-year horizons from a Medicare perspective. Model probabilities were informed by multicenter retrospective analyses published in 2023 comparing TMT with RC. The index patient was aged 71 years, with clinical stage T2-4aN0M0 MIBC, solitary tumor smaller than 7 cm, no or unilateral hydronephrosis, adequate bladder function, and lack of multifocal or extensive carcinoma in situ. Patients unfit for RC, radiation, or cisplatin-based chemotherapy were excluded.

Exposures: TMT and RC.

Main outcome and measures: Primary outcomes included effectiveness measured in quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICER) using a willingness-to-pay threshold of $100 000 per QALY. Sensitivity analyses were performed to assess the robustness of the model.

Results: For the index patient, at 5 years, the average cost was $30 525 higher for TMT than RC. Average QALYs were 3.87 and 3.94 for RC and TMT, respectively. As such, TMT was not cost-effective at 5-year (ICER, $464 291 per QALY) or 10-year (ICER, $308 638 per QALY) time horizons. On 1-way sensitivity analyses, TMT would become cost-effective if (1) TMT costs were less than $17 605; or (2) TMT resulted in an 11.6% improvement in metastasis-free survival relative to RC.

Conclusions and relevance: In this economic evaluation study of TMT and RC for treatment of MIBC, TMT was associated with improved quality of life but was not cost-effective relative to RC at 5 and 10 years given higher treatment costs. These findings highlight the importance of developing policy initiatives that help reduce TMT costs and of providing patients with accurate expectations of long-term toxic effects to help guide preference-sensitive care.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Joyce reported consulting fees from Johnson & Johnson outside the submitted work. Dr Boorjian reported consulting fees from Ferring, ArTara, Prokarium, and Johnson & Johnson outside the submitted work. Dr Gore reported nonfinancial support for advisory work from Astellas Pharmaceuticals, Inc outside the submitted work. Dr Khaki reported grants from Pfizer, Janssen, 23andMe, and Acrivon Therapeutics outside the submitted work; and he reported uncompensated consulting or advisory work with Janssen and Pfizer/Astellas outside the submitted work. Dr Williams reported consulting or advisory board fees from Janssen, Photocure, Merck, Valar Labs; he reported service as a section editor for BJU International and speaker fees from American Urological Association during the conduct of the study. Dr Smith reported grants from Patient-Centered Outcomes Research Institute, Agency for Healthcare Research Quality, Genentech, Merck-RTI, and National Institutes of Health outside the submitted work. Dr Sharma reported compensated work as part of a scientific advisory board and stock ownership from Immunity Bio outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Tornado Diagram of ICER 1-Way Sensitivity to Model Parameters
GU indicates genitourinary; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life year; RC, radical cystectomy; TMT, trimodal therapy.
Figure 2.
Figure 2.. Two-Way Sensitivity Analyses Comparing Costs and Probability of Progression for RC vs TMT
RC indicates radical cystectomy; MIBC, muscle-invasive bladder cancer; TMT, trimodal therapy. Blue represents combinations in which RC is cost effective and red represents combinations in which TMT is cost effective.
Figure 3.
Figure 3.. Cost-Effectiveness Acceptability Curve at a 5-Year Time Horizon
RC indicates radical cystectomy; TMT, trimodal therapy.
Figure 4.
Figure 4.. Cost-Effectiveness Scatterplot
Each point represents a simulated outcome on probablistic sensitivity analysis—orange dots indicate simulations in which trimodal therapy was the most cost-effective option; blue dots, simulations for which radical cystectomy was the most cost-effective option. The willingness-to-pay threshold was set at $100 000/quality-adjusted life-year. The 95% CI for all simulation outcomes is represented by the ellipse.
See this image and copyright information in PMC

References

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