Mapping prostate cancer lesions pre/post unsuccessful salvage lymph node dissection employing PSMA-PET

Objectives: The aim of this study was to analyze patterns of persistent versus recurrent or new PET lesions in a selected patient cohort with PSA persistence following salvage lymph node dissection (SLND) and pre/post procedure ⁶⁸Ga-PSMA-11 PET (PSMA-PET).

Methods: 16 patients were included in this multicenter study between June 2013 and April 2018. Inclusion criteria were: a) PSMA-PET performed for biochemical recurrence before SLND (pre-SLND PET) and b) repeat PSMA-PET performed for persistently elevated PSA level (≥0.1 ng/mL) ≥6 weeks after SLND (post-SLND PET). Anonymized data were centrally collected. Image analysis was performed by three independent nuclear medicine physicians applying the molecular imaging TNM system PROMISE. Lesions were confirmed by histopathology, presence on correlative CT/MRI/bone scan or PSA response after focal therapy. Association between PSMA-PET results, presence of local/distant lesions and PSA at the time of PET, PSA nadir, PSA doubling time (PSA-DT) or PSA velocity (PSA-V) was evaluated with non-parametric Mann-Whitney U tests. Overall agreement among three readers was evaluated using Fleiss’s kappa coefficient (κ).

Results: The median PSA nadir after SLND was 0.4 ng/mL (IQR, 0.3-2.5 ng/mL) and the median PSA value at the time of PET post-SLND was 1.2 ng/mL (IQR, 0.6-2.8 ng/mL). PSMA-PET was performed before SLND with a median time of 1 months (IQR, 1-2 months). The median time between SLND and PET post-SLND was 4 months (IQR, 2-6 months). Post-SLND PET identified PCa-lesions in 88% (14/16) of patients with PSA persistence after SLND. Median PSA was 1.2 ng/mL (IQR, 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, 10/16 had at least one lesion already detected at baseline (63% PET persistence); 4/16 had new lesions only (25% PET recurrence); 2 had no disease on post-SLND PET. All validated regions (11 regions in 9 patients) were true positive. 9/14 (64%) patients underwent repeat local therapies after SLND (7/14 radiotherapy, 2/14 surgery). There was a statistically significant association between higher PSA (p=0.047) or shorter PSA-DT (p=0.018) at the time of PET and presence of distant lesions. Longer PSA-DT was significantly associated with presence of local lesions only (p=0.02). Overall interpretation among three readers had fair agreement for the local prostate bed (Fleiss’ κ 0.33) and substantial to almost-perfect agreement for pelvic nodes (κ 0.69) and distant metastases (κ 0.68). PET positive pelvic nodes presented with intense PSMA uptake (median SUV_max 15; IQR 9-21), however most were not enlarged by CT criteria (median short diameter 0.8 cm; IQR 0.5-0.9).

Conclusions: Comparison between pre- and post-salvage lymph node dissection PSMA-PET revealed disease patterns in patients with biochemical persistence: PSMA-PET identifies locations of persistent disease in about two thirds of patients with unsuccessful SLND. Post-SLND PET further detects new or potentially growing metastases. About two thirds of patients underwent repeat local therapies after unsuccessful SLND, indicating potential value of accurate PSMA-PET staging for PSA persistence.