Evolution of darolutamide evidence base: review of new data from international congresses and their role in personalization of systemic therapy selection

Prostate cancer remains one of the leading causes of cancer morbidity and mortality among men worldwide. Over the past decade, the approaches to systemic therapy of advanced prostate cancer have undergone fundamental changes. While androgen-deprivation therapy as monotherapy was previously considered the standard of care, the accumulated body of evidence now strongly supports the need for early treatment intensification using androgen signaling inhibitors and/or docetaxel, as well as their combinations. This strategy significantly improves disease control and extends patient survival. Among second-generation androgen receptor inhibitors, darolutamide holds a distinct position due to its unique chemical structure, which provides high selectivity, minimal blood–brain barrier penetration, and a favorable drug–drug interaction profile. The efficacy and safety of darolutamide have been confirmed in several large-scale international phase III trials encompassing various stages of the disease – from non-metastatic castration-resistant to metastatic hormone-sensitive prostate cancer – both in combination with androgen-deprivation therapy and as part of triplet therapy with docetaxel. However, no matter how robust the evidence from randomized registration trials may be, they cannot provide exhaustive answers to all questions encountered in routine clinical practice. Strict patient selection criteria, fixed treatment regimens, and predefined endpoints limit the generalizability of results to the broader patient population. The ARASAFE, ARASEC, and ARACOG studies, the results of which were presented at major international congresses in 2026, are designed to address these gaps. The aim of this review is to summarize and analyze the data from these studies, define their place, and elucidate their role in facilitating the transition toward a personalized model of systemic therapy selection for patients with advanced prostate cancer.