Brief Title: INTROSPECT: Intraoperative PSMA PET/CT Imaging During Radical Prostatectomy

Overview

During prostate cancer surgery, the surgeon aims to remove the tumor completely while preserving the surrounding tissue responsible for urinary continence and sexual potency. However, during surgery, it can be difficult to distinguish cancerous tissue from surrounding healthy tissue and therefore to determine the exact extent of the tumor. As a result, cancer cells may sometimes remain at the edge of the removed prostate, resulting in what is known as a positive surgical margin. Currently, positive surgical margins are identified by histopathology of the prostate specimen, with the results becoming available several days after surgery. The long-term goal of intraoperative imaging is to provide surgeons with information about tumor extent and surgical margins while the operation is still ongoing. This information could allow surgeons to remove additional cancerous tissue during the same procedure while helping preserve surrounding healthy structures. This pilot study INTROSPECT is an initial step toward this goal. INTROSPECT is a prospective pilot study at Geneva University Hospitals evaluating a PET/CT Scanner (AURA-10, Xeos Medical, Belgium) to analyze the prostate specimen directly in the operating room (results in 12 minutes). We plan to include 30 participants. They will all receive an injection of a radiotracer (gallium-68 PSMA-11) at the beginning of surgery. Images will be then compared to the microscopic evaluation to find out how accurately they show the location and extent of the cancer. In this pilot study, the PET/CT findings will not be used to modify the surgical procedure or to remove additional tissue. The study is designed to determine whether the technique is sufficiently accurate and feasible to support future studies evaluating its use for real-time surgical decision-making. The study will also assess radiation exposure to operating room personnel and explore methods for interpreting and segmenting the PET images.

Intraoperative Margin Assessment (IMA) in Robotic-Assisted Radical Prostatectomy (RARP) has the potential to reduce the 30% Positive Surgical Margin (PSM) rate. Nevertheless, the leading technique, NeuroSAFE, is based on the Intraoperative Frozen section (IFS) of the lateral halves of the prostate, which, despite demonstrated oncological benefits comes with several drawbacks. First, implementation is largely restricted to specialized center as it requires dedicated pathology equipment (cryostat) and a uropathologist team trained to the technique. Secondly, apical and basal regions are not assessed therefore missing potential margins, frequently located in the apex. Finally, results are obtained in 45 minutes, potentially increasing operating time. In this context intraoperative PSMA-PET margin assessment has been recently introduced using the CE-marked AURA-10 Device (Xeos Medical, Belgium) which can provide results within 12 minutes. Several previous studies confirmed the feasability of the procedure in the oncological settings. Regarding prostate cancer, only patients presenting high-risk prostate cancer were included, with a detection of 67% to 100% of PSM. Unfortunately, available evidence remains preliminary with several aspects requiring further investigation (population which can benefit of the technology, validation against histopathology, image interpretation \[inter-reader agreement, segmentation methods\] …). Also, clinical implementation requires a characterization of staff radiation exposure and residual specimen activity. To address these questions, we designed INTROSPECT, a prospective IDEAL Stage 2a, single center, pilot study at Geneva University Hospitals. We aim to enroll 30 patients with intermediate or high-risk prostate cancer (PCa) scheduled for RARP. Eligibility requires uptake of the index lesion on preoperative PSMA PET imaging and an indication for radical prostatectomy after multidisciplinary Tumor Board presentation. Participants will undergo RARP with lymph node dissection when clinically indicated. The research procedures include intraoperative intravenous administration of gallium-68 PSMA-11 at 1.0 MBq/kg. The freshly resected prostate is placed in a dedicated holder and scanned in the operating room. The primary objective is to evaluate the concordance between ex-vivo PSMA and final histopathology. Secondary objectives include image interpretability evaluation and concordance with preoperative imaging modalities. We will also evaluate occupational exposure and residual specimen activity.