Robot-Assisted Prostate-Specific Membrane Antigen-Radioguided Surgery in Primary Diagnosed Prostate Cancer

Abstract

The objective of this study was 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). Methods: Men with primary high-risk PCa (≥ cT3a, International Society of Urological Pathology (ISUP) grade group ≥ 3 or prostate-specific antigen of ≥ 15 ng/mL) with potential lymph node metastasis (Briganti nomogram risk > 10% or on preoperative imaging) were enrolled in the study. Patients underwent staging ⁶⁸Ga-PSMA PET/CT scanning. Preoperatively, a ^99mTc-labeled PSMA ligand (^99mTc PSMA I&S; 500 MBq) was administered followed by SPECT/CT. A RARP including extended pelvic lymph node dissection was performed, with intraoperative tracing of PSMA-avid tissues using a prototype DROP-IN γ-probe. Resected specimens were also measured ex vivo. Histopathologic 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, 68 y, and prostate-specific antigen, 9.15 ng/mL). Most of the patients harbored ISUP 5 PCa (75%) and had avid lymph nodes on preoperative PSMA PET (64%). The DROP-IN probe aided resection of PSMA-avid (out-of-template) lymph nodes and residual disease at the prostate bed. Eleven metastatic lymph nodes were identified by the probe that were not observed on preoperative ⁶⁸Ga-PSMA PET/CT. Of the 74 extraprostatic tissue specimens that were resected, 22 (29.7%) contained PCa. The sensitivity, specificity, positive predictive value, and negative predictive value of inpatient use of the γ-probe were 76% (95% CI, 53%-92%), 69% (95% CI, 55%-81%), 50%, and 88%, respectively. Ex vivo, the diagnostic accuracy was superior: 76% (95% CI, 53%-92%), 96% (95% CI, 87%-99%), 89%, and 91%, respectively, for sensitivity, specificity, positive predictive value, and negative predictive value. Of the missed lymph nodes in vivo (n = 5) and ex vivo (n = 5), 90% were micrometastasis (≤3 mm). No complications greater than Clavien-Dindo Grade I occurred. 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 extended pelvic lymph node dissection. Further improvement of the detector technology may optimize the capabilities of robot-assisted ^99mTc-based PSMA-radioguided surgery.

Keywords: extended pelvic lymph node dissection; image-guided surgery; prostate cancer; prostate-specific membrane antigen; robot-assisted surgery.

Graphical abstract

FIGURE 1.

(A) Europrobe 3.2 console (Eurorad, S.A.) providing visual and acoustic count feedback. (B) Insertion of DROP-IN γ-probe and 12-mm assistant laparoscopic port through the Alexis system. (C and D) Intraoperative use of the DROP-IN γ-probe to obtain counts from left obturator lymph node template region (C) and prostate bed (D).

FIGURE 2.

Abdominal CT scan (top), PSMA PET/CT scan (middle), and SPECT/CT scan (bottom). Suspicion for left mesorectal lymph node involvement on preoperative ⁶⁸Ga-PSMA PET/CT in patient 12 (SUV_max, 49). Probe successfully identified node (in vivo node count of 183) and final pathology showed 8-mm malignant lymph node. Red circles indicate a lymph node metastasis suspected on preoperative imaging, that was subsequently correctly identified by the probe and histologically confirmed to be malignant.