Hence, in this complex scenario focused on identifying both disease biomarkers and novel and effective treatments that will benefit patients with PCa, this review centers on the current scene of different Phosphatidylinositol-3-kinase (PI3K) signaling pathway inhibitors, either as monotherapy or in combination treatments in PCa, and the treatment outcomes involved in both preclinical and clinical trials. Here, PIK3CA is linked to posterior cortical atrophy.