The performance of PSMA-RGS strongly depends on the definition of suspicious nodes adopted, with a Target-to-Background (TtB) ratio ≥2 previously suggested; however, this threshold was based on studies that focused on men treated in the recurrence setting.5,7 Based on these premises, we conducted ad interim analyses on the first 30 patients who underwent PSMA-RGS at the time of robot-assisted radical prostatectomy (RARP) with an extended pelvic lymph node dissection (ePLND), enrolled in a phase II, single-institution, prospective study (NCT04832958). Our analyses evaluated the performance characteristics and clinical implications of different TtB ratios adopted (≥2 vs. ≥3 vs. ≥4), comparing them with preoperative PSMA PET and histopathological findings at final pathology.
At a per-region analysis, sensitivity, specificity, and accuracy for a TtB ratio ≥2 vs. ≥3 vs. ≥4 were 72%, 88%, and 87% vs. 54%, 98%, and 92% vs. 36%, 99% and 91%, respectively. Using PSMA PET to select ePLND candidates in case of positive spots would have spared 77% ePLNDs (n=23) at the cost of missing 13% (n=3) pN1 patients. A TtB ratio ≥2 at RGS identified 8 (24%) suspicious areas not detected by PSMA PET, of these 5 (63%) harbored lymph node invasion, with one more pN1 patient (11%) that would have been missed by PSMA PET. Adoption of a TtB ratio ≥2 vs. ≥3 vs. ≥4, would have allowed to spare 18 (60%) vs. 23 (77%) vs. 24 (80%) ePLNDs, missing 2 (11%) vs. 3 (13%) vs. 4 (17%) pN1 patients, respectively.
A TtB ratio ≥3 exhibited perfect correspondence with preoperative PSMA PET on a per-patient analysis. Nonetheless, both preoperative PSMA PET and the use of a TtB ratio ≥3 were characterized by a substantial risk of missing positive nodes at final pathology. A TtB ratio ≥2 was able to identify one additional pN1 patient with less than a 15% increase in ePLNDs. These findings suggest that employing PSMA-RGS and removing nodes only in men with positive intraoperative uptake would slightly increase ePLNDs while enhancing the removal of positive lymph nodes. However, PSMA-RGS was not able to overcome the dimensional limitation of PSMA PET, where no nodal metastases smaller than 3 mm have been identified.
Clinically, our results imply that using PSMA-RGS with a TtB ratio ≥2 could further reduce the residual number of patients with false negative findings at preoperative PSMA PET. In men with negative PSMA PET, the use of PSMA-RGS and sparing an ePLND in men with negative findings at both procedures could further reduce the risk of missing. When considering patients with a positive preoperative PSMA PET or those with very high-risk disease, a TtB ratio ≥2 can still have a role in identifying additional suspicious areas outside the standard ePLND template which should be excised.
Written by: Leonardo Quarta, MD, Division of Oncology/Unit of Urology, Gianfranco Soldera Prostate Cancer Lab, Urological Research Institute (URI), IRCCS San Raffaele Scientific Institute, Milan, Italy
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