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

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.

The aim of this study is to assess the diagnostic ability of FCM for prostate cancer (PCa) identification and grading from PB.

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.

The primary endpoint is to evaluate the ability of FCM to identify cancer 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).

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, κ = 0.84). Inter-rater agreement between pathologists was almost perfect for both HE and FCM for PCa detection (0.98 for HE, κ = 0.95; 0.95 for FCM, κ = 0.86); for cancer grade attribution, only a moderate agreement was reached for both HE and FCM (HE, κ = 0.47; FCM, κ = 0.49).

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.

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.

European urology oncology. 2020 Sep 18 [Epub]

Bernardo Rocco, Maria Chiara Sighinolfi, Marco Sandri, Valentina Spandri, Alessia Cimadamore, Metka Volavsek, Roberta Mazzucchelli, Antonio Lopez-Beltran, Ahmed Eissa, Laura Bertoni, Paola Azzoni, Luca Reggiani Bonetti, Antonino Maiorana, Stefano Puliatti, Salvatore Micali, Maurizio Paterlini, Andrea Iseppi, Francesco Rocco, Giovanni Pellacani, Johanna Chester, Giampaolo Bianchi, Rodolfo Montironi

Department of Urology, Ospedale Policlinico e Nuovo Ospedale Civile S.Agostino Estense Modena, University of Modena and Reggio Emilia, Modena, Italy., Department of Urology, Ospedale Policlinico e Nuovo Ospedale Civile S.Agostino Estense Modena, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: ., Data Methods and Systems Statistical Laboratory, University of Brescia, Brescia, Italy., School of Medicine and Surgery, University of Modena and Reggio Emilia, Modena, Italy., Department of Pathology, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy., Department of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia., Department of Pathology, University of Cordoba, Cordoba, Spain., Department of Urology, Ospedale Policlinico e Nuovo Ospedale Civile S.Agostino Estense Modena, University of Modena and Reggio Emilia, Modena, Italy; Urology Department, Faculty of Medicine, Tanta University, Tanta, Egypt., Department of Human Anatomy, University of Modena and Reggio Emilia, Modena, Italy., Department of Pathology, University of Modena and Reggio Emilia, Modena, Italy., Columbus Clinic, Milan, Italy., Dermatology Department, University of Modena and Reggio Emilia, Modena, Italy., Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy.

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