Background: Recently several new treatment regimens have been approved for treating mHSPC, building on the previous standard of care 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 Abiraterone+Prednisone+ADT+Docetaxel (AAD). There are no current predictive biomarkers for choosing any specific regimen. The goal of this study was to determine the cost-effectiveness of these new treatments from the US public sector perspective with a lifetime horizon. Methods: We developed a partitioned survival model in which mHSPC patients 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 clinical trials included 7,208 patients. 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 and subsequent therapies, terminal care, and for managing grade 3-4 drug related adverse events, and were obtained from the Federal Supply Schedule and published literature. Results: Average lifetime costs ranged from $154,139 (AAP) to $770,848 (DAD) and mean QALYs ranged from 3.33 (ADT) to 5.08 (ET). All treatment strategies other than AAP and ET were eliminated due to dominance. Compared to AAP, the incremental cost-effectiveness ratio for ET was $484,943/QALY. Results from our analysis including all regimens are shown. Conclusions: Our simulation model found that ET in mHSPC state yielded the most QALYs and would be the most cost-effective option with a WTP threshold as high as $500,000/QALY. However, for a WTP threshold of $150,000/QALY, AAP was the most cost-effective treatment strategy.

ADT: androgen deprivation therapy, QALY: quality-adjusted life-year, ICER: incremental cost-effectiveness ratio.

Outcomes were discounted at an annual rate of 3% to reflect present value; All costs were in 2021 US dollars.