Androgen receptor pathway inhibitor intensification in non-metastatic hormone-sensitive prostate cancer: current evidence and clinical implications.

Prostate cancer is the most common malignancy in men. Although frequently diagnosed at localized stages, a substantial proportion present high-risk features associated with biochemical recurrence and progression. In non-metastatic hormone-sensitive prostate cancer (nmHSPC), standard treatment has traditionally consisted of local therapy combined with androgen deprivation therapy (ADT), but recent advances have reshaped the therapeutic landscape. The addition of androgen receptor pathway inhibitors (ARPIs) to ADT has demonstrated substantial survival benefits in metastatic hormone-sensitive disease, providing the rationale for exploring treatment intensification in earlier stages. Modern imaging techniques, particularly PSMA PET, enable detection of occult metastatic disease influencing treatment selection. Emerging evidence from randomized and phase II-III studies suggests that ARPI intensification combined with radiotherapy, surgery, or salvage approaches may improve disease control in selected high-risk nmHSPC populations. This narrative review summarizes the evidence supporting ARPI intensification in nmHSPC and discusses the clinical implications of recent advances.