The aim of this study was to analyze patterns of persistent versus recurrent or new PET lesions in a selected patient cohort with prostate-specific antigen (PSA) persistence after salvage lymph node dissection (SLND) and pre-procedure and post-procedure prostate-specific membrane antigen (PSMA) ligand PET. Methods: Sixteen patients were included in this multicenter study. The inclusion criteria were PSMA PET performed for biochemical recurrence before SLND (pre-SLND PET) and repeat PSMA PET performed for a persistently elevated PSA level (≥0.1 ng/mL) at least 6 wk after SLND (post-SLND PET). Image analysis was performed by 3 independent nuclear medicine physicians applying the molecular imaging TNM system PROMISE. Lesions were confirmed by histopathology, presence on correlative CT/MRI/bone scanning, or PSA response after focal therapy. Results: Post-SLND PET identified prostate cancer lesions in 88% (14/16) of patients with PSA persistence after SLND. Median PSA was 1.2 ng/mL (interquartile range, 0.6-2.8 ng/mL). Disease was confined to the pelvis in 56% of patients (9/16), and most of these men had common iliac (6/16, 38%) and internal iliac lymph node metastases (6/16, 38%). Extrapelvic disease was detected in 31% of patients (5/16). In pre- and post-SLND PET comparison, 10 of 16 had at least one lesion already detected at baseline (63% PET persistence), 4 of 16 had new lesions only (25% PET recurrence), and 2 had no disease on post-SLND PET. All validated regions (11 regions in 9 patients) were true-positive. Nine of 14 (64%) patients underwent repeat local therapies after SLND (7/14 radiotherapy, 2/14 surgery). Conclusion: SLND of pelvic nodal metastases was often not complete according to PSMA PET. About two thirds of patients had PET-positive nodal disease after SLND already seen on pre-SLND PSMA PET. Notably, about one quarter of patients had new lesions, not detected by presurgical PSMA PET.
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