Circulating tumor DNA-guided treatment decision in metastatic castration-resistant prostate cancer patients: a cost-effectiveness analysis.

Background: The androgen receptor pathway inhibitors (ARPI), abiraterone acetate and enzalutamide, are commonly used in first-line treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). However, early resistance to ARPI treatment occurs frequently. Traditionally, the response is evaluated 3-6 months after the start of treatment. However, recent findings indicate that by detecting circulating tumor DNA (ctDNA) at baseline and 4 weeks after ARPI treatment initiation, patients with a nondurable response can be identified after 4 weeks of treatment, enabling an early switch to alternative treatments.

Objective: This study aims to evaluate the cost-effectiveness of ctDNA-guided treatment switch after 4 weeks of ARPI therapy in mCRPC patients compared to standard of care.

Design: A cost-effectiveness analysis.

Methods: A cost-effectiveness analysis was conducted by creating a Markov state transition model to simulate progression, mortality, and treatment costs over a 5-year time horizon comparing ctDNA-guided care versus standard of care. The outcomes measured were incremental treatment costs per life-years and quality-adjusted life-years (QALYs) gained.

Results: The analysis showed an incremental cost-effectiveness ratio of €65,400.86 per QALY gained and an incremental net monetary benefit of €2716.62. Thereby, the use of ctDNA-guided treatment was cost-effective in comparison to standard care in 74% of the simulations using a willingness-to-pay threshold of €80,000 per QALY gained.

Conclusion: Our study demonstrated the cost-effectiveness of using a ctDNA-guided early therapy switch in non-responders after only 4 weeks of first-line ARPI therapy in mCRPC patients. This paves the way for implementing ctDNA-guided treatment decisions in clinical practice.