Locally advanced prostate cancer (LAPC) is associated with a higher risk of recurrence and metastasis. Perioperative intensified systemic therapy may contribute to tumor downstaging. However, clinical evidence supporting darolutamide-based treatment in LAPC remains limited, and biomarker-informed treatment in this setting is not well established. We report the case of a 70-year-old man with cT4N1M0 LAPC without PTEN or RB1 loss by immunohistochemistry (IHC). At presentation, the patient’s total