Radiation Therapy in Node-Positive Prostate Cancer: Current Evidence and Future Directions

The management of node-positive prostate cancer (N1 PCa) remains a subject of ongoing debate, with growing evidence supporting the role of radiation therapy (RT) alongside systemic therapy. Traditionally, N1 disease was considered metastatic; however, advancements in imaging and treatment have redefined its clinical relevance. This narrative review evaluates current evidence, focusing on recent literature and ongoing clinical trials in N1 PCa, both in the definitive and postoperative setting. Prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET/CT) has significantly improved staging accuracy, leading to stage migration and increased consideration of RT for patients with cN1 disease. Both retrospective and prospective studies suggest that RT combined with androgen deprivation therapy (ADT) improves survival compared to ADT alone. Robust data from large clinical trials and ongoing studies support the use of whole-pelvic RT (WPRT) with dose escalation to involved nodes. The optimal management of postoperative pN1 disease remains controversial, with strategies ranging from observation to early salvage or adjuvant RT, often combined with systemic therapy. The ideal RT volume, dose, and systemic therapy combinations continue to be investigated. However, several ongoing trials are paving the way for more refined and effective treatment approaches. This review highlights key trials that may significantly improve the management of N1 PCa in the near future.