5081 Background: Recently several new drug treatment regimens have been approved in mHSPC state, building on using androgen deprivation therapy (ADT) alone. These include docetaxel + ADT (DA), Abiraterone Acetate + Prednisone + ADT (AAP), Apalutamide + ADT (AAT), Enzalutamide + ADT (ET), Darolutamide + Docetaxel + ADT (DAD) and AAP + ADT + Docetaxel (AAD). At present, there are no predictive biomarkers for choosing a specific drug regimen over the other. The goal of this study was to conduct an economic evaluation of FDA-approved standard of care drug regimens in the current management of mHSPC state to determine a cost-effective optimal treatment from the US public sector (Veterans Affairs-VA) perspective with a 10-year time horizon. Methods: We developed a partitioned survival model in which mHSPC patients (pts) transitioned between three health states (progression free, progressive disease to castrate resistance state, and death) at monthly intervals based on Weibull survival model estimated from published Kaplan-Meier curves using a network meta-analysis. A Bayesian network meta-analysis of seven randomized clinical trials included 7,208 mHSPC pts. The effectiveness outcome in our model was quality-adjusted life-years (QALYs) with utility values obtained from published literature. Costs in our model included those associated with treatment regimens, subsequent therapies, terminal care, and for managing grade 3-4 drug related adverse events. Costs were obtained from the Federal Supply Schedule and published literature. Incremental cost-effectiveness ratios (ICERs) were calculated for nondominated treatments. Results: Average 10-year costs ranged from $32,697 (ADT) to $649,622 (DAD). Mean QALYs ranged from 3.25 (ADT) to 4.57 (ET). Treatment with DAT, EAD, and DAD were eliminated due to dominance (i.e. they were more costly and less effective than other treatments). AAT was the most cost-effective strategy at a willingness-to-pay threshold of $100,000/QALY (ICER = $70,150/QALY). Results from our analysis for all regimens are shown. Conclusions: Our CEA simulation model found AAT is an optimal cost-effective first-line treatment strategy in mHSPC state from a public (VA) payer perspective. [Table: see text]