Intraoperative technologies to assess margin status during radical prostatectomy - a narrative review

Positive surgical margin (PSM) is a frequent concern for surgeons performing radical prostatectomy for prostate cancer (PCa). PSM are recognized as risk factors for earlier biochemical recurrence and expose patients to adjuvant or salvage treatments such as external radiotherapy and hormonotherapy. Several strategies have been established to reduce PSM rate, while still allowing safe nerve-sparing surgery. Precise preoperative staging by multiparametric magnetic resonance imaging (mpMRI) and fusion biopsy is recommended to identify suspicious areas of extracapsular extension (ECE) that warrant special attention during dissection. However, even with optimal imaging, ECE can be missed, some cancers are not well defined or visible, and capsular incision during surgery remains an issue. Hence, intraoperative frozen section techniques, such as the neurovascular structure-adjacent frozen section examination (NeuroSAFE) have been developed and lately widely disseminated. The NeuroSAFE technique reduces PSM rate while allowing higher rate of nerve-sparing surgery. However, its use is limited to high volume or expert center because of its high barrier-to-entry in terms of logistics, human resources and expertise, as well as cost. Also, NeuroSAFE is a time-consuming process, even in expert hands. To address these issues, several technologies have been developed for an ex vivo and in vivo use. Ex vivo technology such as fluorescent confocal microscopy and intraoperative PET-CT require the extraction of the specimen for preparation, and digital images acquisition. In vivo technology, such as augmented reality based on mpMRI images and PSMA-fluorescent guided surgery have the advantage to provide an intracorporeal analysis of the completeness of the resection. The current manuscript provides a narrative review of established techniques, and details several new and promising techniques for intraoperative PSM assessment.