Oncologic outcomes of salvage radiotherapy and lymphadenectomy for positron emission tomography-positive lymph nodes in biochemical recurrence: A systematic review to inform treatment decisions.

Introduction: Positron emission tomography (PET) scans are widely used for detecting biochemical recurrence (BCR) in prostate cancer, yet evidence for salvage treatments of PET-positive lymph nodes remains limited. This study aimed to analyze the oncologic outcomes of salvage treatments, specifically lymph node dissection (LND) and radiotherapy (RT), in patients with BCR and PET-positive lymph node recurrence. Methods: Systematic reviews and meta-analyses were performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of PubMed, Cochrane, and Web of Science databases up to June 2023 was conducted. Inclusion criteria encompassed patients with BCR and PET-positive lymph node recurrence following definitive prostate cancer treatment, who underwent salvage LND or RT. Results: A total of 38 publications involving 3,559 patients (1391 LND, 2168 RT) were included. Pooled incidence rates after LND and RT were as follows: prostate-specific antigen (PSA) response (56.4% vs. 78.9%), PSA progression (61.3% vs. 36.0%), image progression (44.9% vs. 34.9%), systemic progression (41.3% vs. 35.0%), overall mortality (3.0% vs. 4.8%), and cancer-specific mortality (8.4% vs. 4.1%). Subgroup analyses by prostate-specific membrane antigen (PSMA) PET scan, PSA level ≤2 ng/ml at PET scan, and androgen deprivation therapy usage with salvage therapy revealed varied outcomes. Conclusions: Despite salvage LND or RT, about half of BCR patients with PET-positive nodal recurrence showed disease progression, suggesting limited effectiveness of focal therapies alone. RT appeared to provide better short-term disease control than LND, highlighting the importance of treatment selection. The study underscores the necessity for further investigation into optimal salvage management strategies for BCR using PET in prospective clinical studies.