The treatment landscape of metastatic hormone-sensitive prostate cancer (mHSPC) has changed radically in recent years. Androgen deprivation therapy (ADT) alone was for decades the standard of care for treating mHSPC. This changed when studies showed that the addition of docetaxel chemotherapy or abiraterone acetate to ADT significantly increases overall survival of patients with mHSPC, followed by more recent evidence showing the efficacy of androgen receptor antagonists, such as enzalutamide and apalutamide, in this setting. While this rapid therapeutic evolution is welcome, it presents clinicians with a crucial challenge: the choice of treatment selection and sequencing. In the first-line setting there are no comparative data currently available to guide treatment choice between the different available regimens, and no prospective data to guide clinical decision after progression. Decisions on treatment will now need to be personalised based on indirect comparison of the available efficacy data from multiple phase 3 studies, together with considerations of disease volume, comorbidities, treatment aims, toxicity profile and cost reimbursement within the healthcare setting. Here, we provide an overview of the clinical trial data to date and propose some biological and clinical insights which may be helpful in making decisions on treatment selection and sequencing.

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