Pelvic Lymph Node Staging With PSMA PET in Prostate Cancer: Surgical Validation With Implications for Radiotherapy Planning.

[BACKGROUND] Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) is increasingly used for pelvic nodal staging in prostate cancer and is often incorporated into radiotherapy decision-making. However, the negative predictive value of PSMA PET/CT for microscopic nodal disease remains imperfect. This study aimed to determine the true rate of occult pelvic lymph node metastases in patients with negative PSMA PET/CT using surgical histopathology as the reference standard.

[METHODS] This retrospective surgical validation study included 51 patients with intermediate- or high/very high-risk prostate cancer and negative pelvic lymph node findings on preoperative ⁶⁸Ga-PSMA PET/CT. All patients underwent radical prostatectomy with extended pelvic lymph node dissection between January 2021 and December 2024. Histopathological lymph node status (pN) served as the primary outcome. Clinical, imaging, and pathological variables were analyzed for associations with occult nodal metastases.

[RESULTS] Despite negative PSMA PET/CT findings, 6 of 51 patients (11.8%) had histopathologically confirmed pelvic lymph node metastases. Patients with pN+ disease were significantly older (median: 70 vs. 64 years, p = 0.019) and had higher preoperative PSA levels (mean: 24.85 vs. 12.95 ng/mL, p = 0.006). pN+ status was also associated with higher preoperative nodal risk scores. No significant differences were observed for Gleason grade group, clinical T stage, lymphovascular invasion, perineural invasion, or cribriform morphology between pN+ and pN- groups.

[CONCLUSION] Negative PSMA PET/CT does not reliably exclude microscopic pelvic lymph node metastases in intermediate- and high/very high-risk prostate cancer. These findings demonstrate a biologically relevant false-negative rate for PSMA-based nodal staging. While this study does not assess radiotherapy outcomes, the presence of occult nodal disease in PSMA-negative patients supports a cautious, risk-adapted approach to treatment de-escalation strategies involving pelvic nodal irradiation.