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

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.

Inclusion criteria

• Diagnosis of intermediate- or high-risk prostate cancer.
• Preoperative PSMA PET staging with positive uptake in the primary tumor.
• Multidisciplinary approval by the urology tumor board for radical prostatectomy and study inclusion.
• Capacity to provide informed consent

Exclusion criteria

• Refusal to participate or withdrawal from the study.
• Inability to follow study procedures, for example because of language difficulties, psychological disorders or dementia.
• Participation in another clinical trial requiring ex vivo prostate tissue for research.
• Prior treatment that may alter PSMA uptake, such as androgen deprivation therapy or radiotherapy.
• Variant prostate cancer histology, such as neuroendocrine cancer.
• Insufficient-quality or unavailable PSMA PET images, including corrupted data, or an incomplete histopathology report.