OBJECTIVES : Multiple systemic treatments are available for metastatic castration-sensitive prostate cancer (mCSPC), with different efficacy and safety and widely varied costs. This study aims to assess their cost-effectiveness from a U.S. health care sector perspective over a lifetime horizon.

METHODS : We built a partitioned survival model with treatment effect derived from a parametric survival network meta-analysis of clinical trials to predict patient health trajectories by treatment strategy. A cohort of simulated patients began with mCSPC and were followed up as they progressed to metastatic castration-resistant prostate cancer and death. Five treatments were compared, including docetaxel, abiraterone acetate, enzalutamide, and apalutamide, in combination with androgen deprivation therapy (ADT), and ADT alone. We measured costs in 2020 U.S. dollars and health outcomes in quality-adjusted life-years (QALYs), with a discount rate of 3%. We estimated drug acquisition costs by Federal Supply Schedule and health state costs by MarketScan Commercial Claims and Medicare Supplemental databases. Cost-effectiveness was measured by the incremental cost-effectiveness ratio (ICER). Uncertainty was tested with deterministic and probabilistic sensitivity analyses.

RESULTS : The most cost-effective treatment was abiraterone acetate plus ADT, with incremental costs of $51,261 and incremental QALYs of 1.35, ICER $51,261 per QALY, compared with ADT alone. Incorporating uncertainties in disease progression, treatment effect, cost, and utility, abiraterone acetate plus ADT had the highest probability of being the most cost-effective treatment, over a range of willingness-to-pay thresholds from $51,261 to $200,000 per QALY. Docetaxel and enzalutamide were dominated by abiraterone acetate with lower QALYs and higher costs. Apalutamide led to incremental QALYs of 0.33 compared with abiraterone acetate but incurred incremental costs of $510,512, ICER $1530,876 per QALY.

CONCLUSIONS : Abiraterone acetate plus ADT is the most cost-effective systemic treatment for mCSPC. An update of the current analysis is necessary when new evidence becomes available from ongoing clinical trials and when drug prices change.