Radioguided Surgery for Prostate Cancer - Beyond the Abstract
PSMA-RGS employs gamma-ray detection technology to intraoperatively identify tissue with high uptake of radiolabeled PSMA-targeting tracers, providing real-time feedback to the surgeon regarding the presence of malignant cells. Over recent years, the development of PSMA ligands labeled with gamma-emitting radionuclides such as 111In-PSMA-I&T and 99mTc-PSMA-I&S has been established. Among these, 99mTc-PSMA-I&S is the most widely used due to the limitations associated with 111In-PSMA-I&T, which include higher cost, suboptimal pharmacokinetics, greater radiation exposure, and restricted availability. In contrast, 99mTc-PSMA-I&S offers several advantages: it is readily accessible from 99Mo/99mTc generators commonly available in nuclear medicine departments and it has favorable in vivo stability and a relatively slow systemic clearance due to strong plasma protein binding, which promote efficient tracer uptake in PC lesions over time and leads to steadily increasing target-to-background (TtB) ratios up to 21 hours after injection. Typically, 99mTc-PSMA-I&S is administered approximately 20 hours prior to surgery, followed by SPECT/CT imaging to confirm tracer uptake and provide quality control for intraoperative navigation.
Originally, PSMA-RGS was introduced in the context of open salvage lymph node dissection (sLND). However, recent technological advancements, particularly the development of a drop-in gamma probe, have enabled its integration into robot-assisted surgery. The drop-in gamma probe is typically introduced via a 15 mm assistant port, usually located above the right iliac crest, and is manipulated intraoperatively by the console surgeon using robotic prograsp forceps. The control unit of the probe delivers both acoustic and numerical feedback correlating with radiotracer activity, thereby allowing precise identification of PSMA-avid LNMs. A lymph node is typically considered positive when the TtB ratio is at least double that of the surrounding homolateral fatty tissue, serving as the background reference. Additionally, ex vivo gamma measurements can be utilized post-excision to confirm successful removal of the radiolabeled lesion or to prompt further exploration in cases of signal absence. Intraoperative assessment using the drop-in gamma probe is primarily conducted at pelvic lymph node stations to guide the resection of LNMs during PSMA-RGS.
This technique first demonstrated its utility in patients undergoing sLND for biochemical recurrence (BCR) with PSMA PET positive findings after primary treatment, and it has recently been extended to patients undergoing robot-assisted radical prostatectomy (RARP), demonstrating its applicability and potential also in primary staging setting.
Written by: Leonardo Quarta, MD, Unit of Urology/Division of Oncology, Gianfranco Soldera Prostate Cancer Laboratory, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy
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