PSMA PET in Lymph Node Staging of Prostate Cancer: From Diagnostic Accuracy to Clinical Decision-Making

Lymph node involvement in prostate cancer has major prognostic and therapeutic implications, yet conventional imaging based on size and morphology remains limited in detecting small-volume metastatic disease. Although extended pelvic lymph node dissection is considered the reference standard for nodal staging, it is invasive, associated with morbidity, and primarily diagnostic in intent. Prostate-specific membrane antigen positron emission tomography (PSMA PET) has reshaped staging by enabling molecular detection of nodal metastases, consistently demonstrating superior accuracy compared with conventional imaging. This narrative review critically evaluates the role of PSMA PET in lymph node staging, with a primary focus on primary diagnosis and selected considerations on biochemical recurrence, focusing not only on diagnostic accuracy but on clinical utility and decision-making. PSMA PET shows high specificity but moderate sensitivity for pelvic nodal metastases, with reduced performance for micrometastatic disease; therefore, a negative scan cannot reliably exclude nodal involvement in high-risk patients. Evidence indicates frequent stage migration and management changes, including refinement of surgical planning, radiotherapy target delineation, and treatment intensification strategies. However, most pivotal therapeutic trials were based on conventional imaging, and long-term outcome data validating PSMA PET-guided treatment adaptations remain limited. We discuss biological rationale, radiotracer characteristics, interpretation frameworks, guideline perspectives, real-world variability in adoption, and current limitations, including false-positive findings, PSMA heterogeneity, and lack of universal standardization. Rather than replacing established staging paradigms, PSMA PET should be integrated within a comprehensive, risk-adapted framework. Ongoing prospective trials will clarify whether molecularly defined nodal staging translates into improved oncologic outcomes and will determine its definitive role in contemporary prostate cancer management.