Current landscape in first-line treatment of metastatic hormone sensitive prostate cancer: a cost-effectiveness focused review

Abstract Contemporary treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has evolved significantly over the past decade with the introduction of upfront combination therapies (ie, ADT plus androgen receptor pathway inhibitors (ARPIs), with or without docetaxel), previously reserved for more advanced stages of the disease. However, the evidence is still controversial regarding the benefit of triple combinations beyond high volume disease (HVD) compared to double combinations, particularly those consisting of ADT + ARPIs. In addition, financial considerations regarding net benefits make these treatment regimens an unfavorable option from a cost-effectiveness standpoint, an element that becomes even more relevant in resource-limited contexts. Considering the lack of head-to-head trials for the direct comparison of triplets vs. ADT + ARPIs in different subgroups (as most evidence of specific combination superiority comes from indirect comparison in meta-analyses and the questionable cost-effectiveness profile triplets have shown), we propose that the current role of triplets is reserved for synchronous, HVD mHSPC in a resource-rich setting. Consequently, our work proposes a treatment algorithm that weighs the OS benefit according to the clinical risk of each patient subgroup and the availability of clinical resources. In this current scenario of abundant options, future research will focus on clarifying the selection of the most appropriate treatment for each patient according to their clinical characteristics and re-evaluating the cost-effectiveness of treatments as new drugs and generics emerge.