Case 2023: Mario (expert opinion by A. Bossi)

ADT alone is certainly not the best option for Mario. In the SPARTAN, PROSPER and ARAMIS trials, apalutamide, enzalutamide and darolutamide have been added to ADT, and all 3 demonstrated an OS benefit compared to ADT + placebo. In these trials patients were staged with conventional imaging. There are currently no randomised clinical trials directly comparing the different options, but there is real-world evidence available comparing these molecules, such as the DEAR study [1]. In this study of 870 patients with nmCRPC who did not receive prior novel hormonal therapy, treatment discontinuation was analysed, as well as progression to the metastatic castration-resistant state. Patients on darolutamide discontinued treatment in 30% of cases, while patients on enzalutamide or apalutamide discontinued in about 40-46% of cases. In terms of progression to the metastatic castration-resistant state, patients on darolutamide progressed in 18% of cases, while patients on enzalutamide or apalutamide progressed in 28% of cases. Additionally, the drugs that Mario is taking to control hypertension and deep vein thrombosis, are prone to drug-to-drug interactions, which are more limited with darolutamide [2]. Therefore, the best choice for Mario would be adding darolutamide to ADT.

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