Urothelial carcinoma (UC) demonstrates significant molecular and histologic heterogeneity. The WHO 2022 classification has hinted at adding molecular signatures to the morphologic diagnosis. As morphology and associated molecular repertoire may potentially translate to choices of and response to therapy and relapse rate, broader acceptability of recognizing these key features among uropathologists is needed. This prompted an international survey to ascertain the practice patterns in classical/subtype UC among uropathologists across the globe.
A survey instrument was shared among 98 uropathologists using SurveyMonkey software. Anonymized respondent data were analysed. The response rate was 85%. A majority were in concordance with the profiles of luminal (93%) and basal (82%) types. Opinion on the FGFR3 testing platform was variable. While 95% concurred that TERT promoter mutation is the key driver in UC, 72% had the opinion that APOBEC mutagenesis is the main signature in muscle invasive bladder cancer (MIBC). Uropathologists have divergent opinions on MIBC and ERCC2 mutations. Among the participants, 94% would quantify aggressive micropapillary and sarcomatoid histology, while 88% would reevaluate another transurethral resection of the bladder tumour specimen in nonmuscle invasive tumour with micropapillary, small cell, or sarcomatoid histology. A leading number agreed to specific molecular signatures of micropapillary (93%), plasmacytoid (97%), and small cell (86%) subtypes. Ninety-six percent of participants agreed that a small-cell component portends a more aggressive course and should be treated with neoadjuvant chemotherapy and 63% would perform HER2/neu testing only on oncologist's request in advanced tumours. Ninety percent agreed that microsatellite instability testing, although not a standard protocol, should be considered in young patients with upper tract UC. Eighty-six percent agreed that UC with high tumour mutational burden would be a better candidate for immunotherapy.
In the era of precision medicine, enhanced understanding of molecular heterogeneity of UC will contribute to better therapeutic options, novel biomarker discovery, innovative management protocols, and outcomes. Our survey provides a broad perspective of pathologists' perceptions and experience regarding incorporation of histomolecular approaches to "personalize" therapy. Due to variable clinical adoption, there is a need for additional data using uniform study criteria. This will drive generation of best practice guidelines in this area for widespread and consistent clinical utility.
Histopathology. 2024 Jul 29 [Epub ahead of print]
Anandi Lobo, Katrina Collins, Seema Kaushal, Andres M Acosta, Mahmut Akgul, Amit K Adhya, Hikmat A Al-Ahmadie, Khaleel I Al-Obaidy, Ali Amin, Mahul B Amin, Manju Aron, Bonnie L Balzer, Rupanita Biswal, Subashish Mohanty, Lisa Browning, Indranil Chakrabarti, Luca Cima, Alessia Cimadamore, Sangeeta Desai, Jasreman Dhillon, Akansha Deshwal, Guillermo G Diego, Preeti Diwaker, Laurence A Galea, Cristina Magi-Galluzzi, Giovanna A Giannico, Nilesh S Gupta, Aiman Haider, Michelle S Hirsch, Kenneth A Iczkowski, Samriti Arora, Ekta Jain, Deepika Jain, Shilpy Jha, Shivani Kandukuri, Chia-Sui Kao, Oleksandr N Kryvenko, Ramani M Kumar, Niraj Kumari, Lakshmi P Kunju, Levente Kuthi, João Lobo, Jose I Lopez, Daniel J Luthringer, Fiona Maclean, Claudia Manini, Rahul Mannan, María G Martos, Rohit Mehra, Santosh Menon, Pritinanda Mishra, Holger Moch, Rodolfo Montironi, Manas R Baisakh, George J Netto, Lovelesh K Nigam, Adeboye O Osunkoya, Francesca Pagliuca, Gladell P Paner, Angel Panizo, Anil V Parwani, Maria M Picken, Susan Prendeville, Christopher G Przybycin, Suvendu Purkait, Francisco J Queipo, B Vishal Rao, Priya Rao, Victor E Reuter, Sankalp Sancheti, Ankur R Sangoi, Rohan Sardana, Swati Satturwar, Rajal B Shah, Shivani Sharma, Mallika Dixit, Monica Verma, Deepika Sirohi, Steven C Smith, Shailesh Soni, Sandhya Sundaram, Meenakshi Swain, Maria Tretiakova, Kiril Trpkov, Gorka MuñizUnamunzaga, Ming Zhou, Sean R Williamson, Antonio Lopez-Beltran, Liang Cheng, Sambit K Mohanty
Department of Pathology, Kapoor Centre of Urology and Pathology, Raipur, India., Department of Pathology, Indiana University Health, Indiana, USA., Department of Pathology, All India Institute of Medical Sciences, New Delhi, India., Department of Pathology, Albany Medical Center, Albany, USA., Department of Pathology, All India Institute of Medical Sciences, Bhubaneswar, India., Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, USA., Department of Pathology, Henry Ford Health System, Detroit, USA., Department of Pathology, Alpert Medical School of Brown University, Providence, USA., Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, USA., Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, USA., Department of Pathology, Bagchi Sri Shankara Cancer Hospital, Bhubaneswar, India., Department of Pathology, SUM Ultimate Medicare Hospital, Bhubaneswar, India., Department of Pathology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK., Department of Pathology, All India Institute of Medical Sciences, Kalyani, India., Department of Pathology, Santa Chiara Hospital of Trento, Trento, Italy., Department of Pathology, Molecular Medicine and Cell Therapy Foundation, c/o Polytechnic University of the Marche Region, Ancona, Italy., Department of Pathology, Tata Memorial Hospital, Mumbai, India., Department of Pathology, Moffitt Cancer Center, Tampa, USA., Department of Pathology, ESI Hospital, New Delhi, India., Department of Pathology, University Gregorio Marañon Hospital, Madrid, Spain., Department of Pathology, University College of Medical Sciences, New Delhi, India., Department of Pathology, Melbourne Pathology, Melbourne, Australia., Department of Pathology, The University of Alabama at Birmingham, Birmingham, USA., Department of Pathology, University of California - Irvine, Irvine, USA., Department of Pathology, University College London Hospitals NHS Foundation Trust, London, UK., Department of Pathology, Brigham and Women's Hospital, Boston, USA., Department of Pathology, University of California - Davis, Davis, USA., Department of Pathology, CORE Diagnostics, Gurgaon, India., Department of Pathology, Advanced Medical and Research Institute, Bhubaneswar, India., Department of Pathology, Cleveland Clinic, Cleveland, USA., Department of Pathology, University of Miami Miller School of Medicine, Miami, USA., Department of Pathology, Dane Diagnostics, Palakkad, India., Department of Pathology, All India Institute of Medical Sciences, Raebareli, India., Department of Pathology, University of Michigan, Ann Arbor, USA., Department of Pathology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary., Department of Pathology, Portuguese Oncology Institute - Porto, Porto, Portugal., Department of Pathology, Cruces University Hospital, Barakaldo, Spain., Department of Pathology, Douglass Hanly Moir Pathology, Sydney, Australia., Department of Pathology, University of Turin, Turin, Italy., Department of Pathology, University Hospital Zurich, Zurich, Switzerland., Department of Pathology, Prolife Diagnostics, Bhubaneswar, India., Department of Pathology, University of Pennsylvania, Philadelphia, USA., Department of Pathology, Institute of Kidney Diseases and Research Center, Ahmedabad, India., Department of Pathology, Emory University School of Medicine, Atlanta, USA., Department of Pathology, Università degliStudidella Campania Luigi Vanvitelli, Caserta, Italy., Department of Pathology, University of Chicago, Chicago, USA., Department of Pathology, Complejo Hospitalario de Navarra, Pamplona, Spain., Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, USA., Department of Pathology, Loyola University Medical Center, Hines, USA., Department of Pathology, University Health Network, University of Toronto, Toronto, Canada., Department of Pathology, Hospital Universitario de A Coruna, A Coruna, Spain., Department of Pathology, Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad, India., Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, USA., Department of Pathology, Homi Bhabha Cancer Hospital, Punjab, India., Department of Pathology, Stanford University, Stanford, USA., Department of Pathology, Sardana Laboratories, Jalandhar, India., Department of Pathology, University of Texas Southwestern Medical Center, Dallas, USA., Department of Pathology, University of California, San Francisco, USA., Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, USA., Department of Pathology, Muljibhai Patel Urological Hospital, Nadiad, India., Department of Pathology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India., Department of Pathology, Apollo Hospitals, Hyderabad, India., Department of Pathology, University of Washington, Seattle, USA., Department of Pathology, University of Calgary, Calgary, Canada., Department of Pathology, Hospital San Jorge, San Juan, Spain., Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts, USA., Department of Pathology, Unit of Anatomical Pathology, Faculty of Medicine, Cordoba University, Cordoba, Spain.