Robot-assisted prostate-specific membrane antigen-radioguided surgery in primary diagnosed prostate cancer

Objectives: To evaluate the safety and feasibility of 99mTc-based prostate-specific membrane antigen (PSMA) robot-assisted radioguided surgery to aid or improve the intraoperative detection of lymph node metastases during primary robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa). Materials and Methods: Men with primary high-risk Pca (≥cT3a, international society of urological pathology (ISUP) Grade Group ≥3 or PSA of ≥ 15 ng/mL) with potential lymph node metastasis (Briganti nomogram risk >10% or on preoperative imaging) were enrolled onto the study. Patients underwent a staging 68Ga-PSMA PET/CT. Pre-operatively a 99mTc-labelled PSMA ligand (99mTc PSMA I 500 MBq) was administrated followed by single-photon emission/CT(SPECT). A RARP including extended pelvic lymph node dissection was performed, with intraoperative tracing of PSMA-avid tissues using a prototype DROP-IN gamma probe. Resected specimens were also measured ex-vivo. Histopathological concordance with probe findings was evaluated. A radiotracer count of ≥ 1.5 times the background reference (in-vivo), and ≥10 (absolute count) in the ex-vivo setting, was considered positive. Results: Twelve patients were included, median age of 68 years and PSA of 9.15 ng/ml. The majority of patients harboured ISUP 5 PCa (75%) and had avid lymph nodes on pre-operative PSMA PET (64%). The DROP-IN probe aided resection of PSMA-avid (out-of-template) lymph nodes and residual disease at the prostate bed. 11 metastatic lymph nodes were identified by the probe that were not observed on pre-operative 68Ga-PSMA PET/CT. Of the 74 extraprostatic tissue specimens that were resected, 22 (29.7%) contained PCa. The sensitivity, specificity, PPV and NPV (95% confidence interval) of inpatient use of the gamma probe was 76% (53-92%), 69% (55-81%), 50% and 88%, respectively. Ex-vivo, the diagnostic accuracy was superior, 76% (53-92%), 96% (87-99%), 89% and 91%, respectively. Of the missed lymph nodes in-vivo (n = 5) and ex-vivo (n = 5), 90% were micrometastasis (≤3mm). No complications occurred greater than Clavien-Dindo Grade I. Conclusion: Robot-assisted 99mTc-based PSMA radioguided surgery is feasible and safe in the primary setting, optimizing the detection of nodal metastases at the time of RARP and ePLND. Further improvement of the detector technology may optimize the capabilities of robot-assisted 99mTc-based PSMA-radioguided surgery.