Feasibility and accuracy of intraoperative molecular PET imaging to improve complete tumor resection

• Applicants: Dr. Christopher Darr; Professor Dr. Ken Herrmann
• Subject Area: Reproductive Medicine, Urology ; Radiology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 535541137

Urological tumors: renal cell carcinoma (RCC), urothelial carcinoma (UC) and prostate cancer (PC) are among the most common solid tumor entities in Germany. In the context of local surgical therapies, the primary goal is to completely resect the cancer while sparing functionally important healthy tissue as much as possible. Especially with the advent of robot-assisted surgery, the percentage of organ-preserving or nerve-sparing interventions is steadily increasing. Currently, nerve-sparing surgery is aimed at in more than 80% of patients. Up to date surgeons have no reliable and accurate tool to intraoperatively detect cancer, which is why standard of care remains visual inspection and palpation as well as targeted frozen section analysis of excised specimen. However, the choice of sampling sites depends mainly on the surgeon. Moreover, standardization is difficult due to the highly variable tumor burden. After prostatectomy for high-risk prostate cancer, approximately 30% of men develop biochemical recurrence. Recently, prostate-specific membrane antigen ligand (PSMA) positron emission tomography (PET) has emerged as an accurate tool to detect PC in both primary staging and at time of biochemical recurrence. In recent years, nephron-sparing renal tumor surgery in the sense of partial nephrectomy or renal tumor enucleation has replaced radical nephrectomy as the standard therapy for localized renal cell carcinoma. This has resulted in an increase in R1 rates with tumor growth approaching the resection margins. This increases the risk of local recurrence, so that repeated surgery with nephrectomy may be indicated. Also in the context of radical removal of the bladder, it has been shown that a rate of R1 resections correlates with the experience of the surgeon and is associated with an increased rate of local recurrence or mortality. Beta particles travel only short distances in biological tissue, thus, providing a detectable signal from cancerous cells with a tissue-specific tracer uptake only within a few millimeters of the tissue's surface, which seems ideal for the assessment of surgical margins in cancer surgery. Intraoperative radioguidance may help surgeons in the detection of extracapsular extension, positive surgical margins and lymph node metastases with the aim of increasing surgical precision and possibly improving oncological outcome. The objective of our project is to assess the feasibility and accuracy of novel intraoperative imaging with a specimenPET/CT in cancer surgery of urological tumors (RCC, UC and PC). After informed consent, patients will undergo PET/CT immediately prior to surgery. If conventional PET/CT has already been performed, low-dose intraoperative injection will be used. Subsequently, standard surgery will be performed and excised specimens will be imaged in the OR ex vivo with the specimenPET/CT in order to identify regions at risk for extracapsular extension of cancer and positive surgical margins.

• DFG Programme: Research Grants
• Co-Investigators: Dr. Pedro Fragoso Costa; Professor Dr. Boris Hadaschik; Dr. Lukas Puellen