Bernardo Rocco1, Maria Chiara Sighinolfi2, Marco Sandri3, Valentina Spandri4, Alessia Cimadamore5, Metka Volavsek6, Roberta Mazzucchelli5, Antonio Lopez-Beltran7, Ahmed Eissa8, Laura Bertoni9, Paola Azzoni9, Luca Reggiani Bonetti10, Antonino Maiorana10, Stefano Puliatti1, Salvatore Micali1, Maurizio Paterlini1, Andrea Iseppi1, Francesco Rocco11, Giovanni Pellacani12, Johanna Chester12, Giampaolo Bianchi1, Rodolfo Montironi13. 1. Department of Urology, Ospedale Policlinico e Nuovo Ospedale Civile S.Agostino Estense Modena, University of Modena and Reggio Emilia, Modena, Italy. 2. Department of Urology, Ospedale Policlinico e Nuovo Ospedale Civile S.Agostino Estense Modena, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: sighinolfic@yahoo.com. 3. Data Methods and Systems Statistical Laboratory, University of Brescia, Brescia, Italy. 4. School of Medicine and Surgery, University of Modena and Reggio Emilia, Modena, Italy. 5. Department of Pathology, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy. 6. Department of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. 7. Department of Pathology, University of Cordoba, Cordoba, Spain. 8. 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. 9. Department of Human Anatomy, University of Modena and Reggio Emilia, Modena, Italy. 10. Department of Pathology, University of Modena and Reggio Emilia, Modena, Italy. 11. Columbus Clinic, Milan, Italy. 12. Dermatology Department, University of Modena and Reggio Emilia, Modena, Italy. 13. Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy.
Abstract
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 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). 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, 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). 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.
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 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). 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, 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). 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.
Authors: Ugo Giovanni Falagario; Oscar Selvaggio; Francesca Sanguedolce; Paola Milillo; Maria Chiara Sighinolfi; Salvatore Mariano Bruno; Marco Recchia; Carlo Bettocchi; Gian Maria Busetto; Luca Macarini; Bernardo Rocco; Luigi Cormio; Giuseppe Carrieri Journal: Diagnostics (Basel) Date: 2022-01-21
Authors: James G Fujimoto; Yue Sun; Lucas C Cahill; Seymour Rosen; Tadayuki Yoshitake; Yubo Wu; Linda York; Leo L Tsai; Boris Gershman Journal: Mod Pathol Date: 2021-11-02 Impact factor: 8.209