Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein expressed in the majority of prostate cancer (PCa). PSMA has an enzymatic function that makes metabolic substrates such as folate available for utilization by PCa cells. Intracellular folate availability drives aggressive tumor phenotype. PSMA expression is, therefore, a marker of aggressive tumor biology. The large extracellular domain of PSMA is available for targeting by diagnostic and therapeutic radionuclides, making it a suitable cellular epitope for theranostics. PET imaging of radiolabeled PSMA ligands has several prognostic utilities. In the prebiopsy setting, intense PSMA avidity in a prostate lesion correlate well with clinically significant PCa (csPCa) on histology. When used for staging, PSMA PET imaging outperforms conventional imaging for the accurate staging of primary PCa, and findings on imaging predict post-treatment outcomes. The biggest contribution of PSMA PET imaging to PCa management is in the biochemical recurrence setting, where it has emerged as the most sensitive imaging modality for the localization of PCa recurrence by helping to guide salvage therapy. PSMA PET obtained for localizing the site of recurrence is prognostic, such that a higher lesion number predicts a less favorable outcome to salvage radiotherapy or surgical intervention. Systemic therapy is given to patients with advanced PCa with distant metastasis. PSMA PET is useful for predicting response to treatments with chemotherapy, first- and second-line androgen deprivation therapies, and PSMA-targeted radioligand therapy. Artificial intelligence using machine learning algorithms allows for the mining of information from clinical images not visible to the human eyes. Artificial intelligence applied to PSMA PET images, therefore, holds great promise for prognostication in PCa management.
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