Digital Biopsy with Fluorescence Confocal Microscope for Effective Real-time Diagnosis of Prostate Cancer: A Prospective, Comparative Study

Background: A microscopic analysis of tissue is the gold standard for cancer detection. Hematoxylin-eosin (HE) for the reporting of prostate biopsy (PB) is conventionally based on fixation, processing, acquisition of glass slides, and analysis with an analog microscope by a local pathologist. Digitalization and real-time remote access to images could enhance the reporting process, and form the basis of artificial intelligence and machine learning. Fluorescence confocal microscopy (FCM), a novel optical technology, enables immediate digital image acquisition in an almost HE-like resolution without requiring conventional processing. Objective: The aim of this study is to assess the diagnostic ability of FCM for prostate cancer (PCa) identification and grading from PB. Design, setting, and participants: This is a prospective, comparative study evaluating FCM and HE for prostate tissue interpretation. PBs were performed (March to June 2019) at a single coordinating unit on consecutive patients with clinical and laboratory indications for assessment. FCM digital images (n = 427) were acquired immediately from PBs (from 54 patients) and stored; corresponding glass slides (n = 427) undergoing the conventional HE processing were digitalized and stored as well. A panel of four international pathologists with diverse background participated in the study and was asked to evaluate all images. The pathologists had no FCM expertise and were blinded to clinical data, HE interpretation, and each other's evaluation. All images, FCM and corresponding HE, were assessed for the presence or absence of cancer tissue and cancer grading, when appropriate. Reporting was gathered via a dedicated web platform. Outcome measurements and statistical analysis: The primaryendpoint is to evaluate the abilityof FCM to identifycancer tissue in PB cores (per-slice analysis). FCM outcomes are interpreted by agreement level with HE (K value). Additionally, either FCM or HE outcomes are assessed with interobserver agreement for cancer detection (presence vs absence of cancer) and for the discrimination between International Society of Urologic Pathologists (ISUP) grade = 1 and ISUP grade > 1 (secondary endpoint). Results and limitations: Overall, 854 images were evaluated from each pathologist. PCa detection of FCM was almost perfectly aligned with HE final reports (95.1% of correct diagnosis with FCM, k = 0.84). Inter-rater agreement between pathologists was almost perfect for both HE and FCM for PCa detection (0.98 for HE, k = 0.95; 0.95 for FCM, k = 0.86); for cancer grade attribution, only a moderate agreement was reached for both HE and FCM (HE, k = 0.47; FCM, k = 0.49). Conclusions: FCM provides a microscopic, immediate, and seemingly reliable diagnosis for PCa. The real-time acquisition of digital images-without requiring conventional processing-offers opportunities for immediate sharing and reporting. FCM is a promising tool for improvements in cancer diagnostic pathways. Patient summary: Fluorescence confocal microscopy may provide an immediate, microscopic, and apparently reliable diagnosis of prostate cancer on prostate biopsy, overcoming the standard turnaround time of conventional processing and interpretation. (C) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.