Joyce, Daniel

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.

572 Background: Bladder preservation with trimodal therapy (TMT), which consists of maximal transurethral resection of bladder tumors followed by chemoradiation, is now included in guidelines with radical cystectomy (RC) as options for definitive management of muscle-invasive bladder cancer (MIBC). Prospective randomized controlled trial data to help guide treatment selection are lacking, and prior efforts to bridge this knowledge gap have failed primarily due to poor accrual. A recent retrospective analysis comparing TMT to RC reported similar oncologic outcomes between these treatments when performed in highly selected patients. However, treatment toxicities and costs vary significantly between these management options. To investigate the impact of these outcomes on relative treatment value, we evaluated the comparative cost-effectiveness of TMT and RC for treatment of MIBC. Methods: Cost-effectiveness was compared between TMT and RC for patients with a solitary, muscle-invasive tumor less than 7cm, no or unilateral hydronephrosis, limited carcinoma in situ, and adequate bladder function (criteria utilized in a recent retrospective comparative series) using a microsimulation model with a 5-year horizon from a Medicare payer perspective. Additionally, a 10-year lifetime horizon was evaluated to better understand the impact of long-term outcome uncertainty on cost-effectiveness. Based on recently published multicenter retrospective propensity score matched data, metastatic progression and survival probabilities were assumed to be equivalent between treatments. Utility values and additional probabilities, including both short and long-term treatment toxicities, were obtained from published literature. Primary outcomes of interest included effectiveness measured in quality adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICER) using a willingness-to-pay threshold of $100,000/QALY. One-way and probabilistic sensitivity analyses were performed to assess the robustness of the model. Results: At 5 years, the average cost was $32,286.35 higher for TMT versus RC. The average QALYs were 3.88 and 3.96 for RC and TMT respectively. TMT was not cost-effective at 5-year (ICER: $379,917.21/QALY) or 10-year (ICER: $222,704.78/QALY) time horizons. On one-way sensitivity analyses, TMT would become cost effective if: 1) TMT costs were less than $16,152; or 2) TMT resulted in a 13.3% improvement in metastasis free survival relative to RC. Conclusions: Although it resulted in similar quality and duration of life, TMT was not cost-effective relative to RC at 5 and 10 years given higher treatment costs. These findings support the role of both TMT and RC in management of MIBC and highlight the need for continued efforts to reduce healthcare costs associated with TMT.

Abstract Background The Surgery in Early Metastatic Seminoma (SEMS) trial examined retroperitoneal lymph node dissection as first-line treatment for patients with isolated 1-3 cm retroperitoneal lymphadenopathy. To date, the standard of care for these patients has been either chemotherapy or radiotherapy. Herein, we evaluated the relative cost-effectiveness of these management strategies. Methods A microsimulation model assessed the cost-effectiveness of retroperitoneal lymph node dissection, chemotherapy, and radiotherapy for stage IIA seminoma. Sensitivity analyses were performed to evaluate model robustness. Retroperitoneal lymph node dissection recurrence probabilities were obtained from the SEMS trial. All other probability and utility values were obtained from published literature. Primary outcomes included costs from a commercial insurer’s perspective, effectiveness (quality adjusted life-years [QALYs]), and incremental cost-effectiveness ratios using a willingness-to-pay threshold of $100 000/QALY. Results At a lifetime horizon, the mean costs per patient for retroperitoneal lymph node dissection, radiotherapy, and chemotherapy were $58 469, $98 783, and $104 096, and the mean QALYs were 40.61, 40.70, and 39.15, respectively. Retroperitoneal lymph node dissection was found to be the most cost-effective approach because of high costs and accrued disutility of chronic toxicities associated with radiotherapy (cost-effectiveness ratios = $433 845/QALY) and chemotherapy (dominated). On 1-way sensitivity analyses, retroperitoneal lymph node dissection was no longer cost-effective if the probabilities of infertility and cardiovascular toxicity after radiotherapy were less than 13% and 16%, respectively, or if the 2-year probability of progression after retroperitoneal lymph node dissection was more than 26%. Conclusions Retroperitoneal lymph node dissection was the most cost-effective treatment approach for stage IIA seminoma. These findings support clinical guideline consideration of including retroperitoneal lymph node dissection as a treatment option for well-selected patients with stage IIA seminoma.