Ekaterina Laukhtina1, Benjamin Pradere2, Keiichiro Mori3, Victor M Schuettfort4, Fahad Quhal5, Hadi Mostafaei6, Reza Sari Motlangh7, Satoshi Katayama8, Nico C Grossmann9, Marco Moschini10, Dmitry Enikeev11, Shahrokh F Shariat12. 1. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia. 2. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, University Hospital of Tours, Tours, France. 3. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan. 4. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 5. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia. 6. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. 7. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 8. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. 9. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, University Hospital Zurich, Zurich, Switzerland. 10. Department of Urology, Luzerner Kantonsspital, Lucerne, Switzerland; Department of Urology and Division of Experimental Oncology, Urological Research Institute, Vita-Salute San Raffaele. 11. Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia. 12. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia; Department of Urology, Weill Cornell Medical College, New York, USA; Department of Urology, University of Texas Southwestern, Dallas, Texas, USA; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan; European Association of Urology Research Foundation, Arnhem, Netherlands. Electronic address: shahrokh.shariat@meduniwien.ac.at.
Abstract
PURPOSE: The present systematic review aimed to identify prognostic values of tissue-based biomarkers in patients treated with neoadjuvant systemic therapy (NAST), including chemotherapy (NAC) and checkpoint inhibitors (NAI) for urothelial carcinoma of the bladder (UCB). MATERIAL AND METHODS: The PubMed, Web of Science, and Scopus databases were searched in August 2020 according to the PRISMA statement. Studies were deemed eligible if they compared oncologic or pathologic outcomes in patients treated with NAST for UCB with and without detected pretreatment tissue-based biomarkers. RESULTS: Overall, 44 studies met our eligibility criteria. Twenty-three studies used immunohistochemistry (IHC), 19 - gene expression analysis, three - quantitative polymerase chain reaction (QT PCR), and two - next-generation sequencing (NGS). According to the currently available literature, predictive IHC-assessed biomarkers, such as receptor tyrosine kinases and DNA repair pathway alterations, do not seem to convincingly improve our prediction of pathologic response and oncologic outcomes after NAC. Luminal and basal tumor subtypes based on gene expression analysis showed better NAC response, while claudin-low and luminal-infiltrated tumor subtypes did not. In terms of NAI, PD-L1 seems to maintain value as a predictive biomarker, while the utility of both tumor mutational burden and molecular subtypes remains controversial. Specific genomic alterations in DNA repair genes have been shown to provide significant predictive value in patient treated with NAC. QT PCR quantification of specific genes selected through microarray analysis seems to classify cases regarding their NAC response. CONCLUSION: We believe that the present systematic review may offer a robust framework that will enable the testing and validation of predictive biomarkers in future prospective clinical trials. NGS has expanded the discovery of molecular markers that are reflective of the mechanisms of the NAST response.
PURPOSE: The present systematic review aimed to identify prognostic values of tissue-based biomarkers in patients treated with neoadjuvant systemic therapy (NAST), including chemotherapy (NAC) and checkpoint inhibitors (NAI) for urothelial carcinoma of the bladder (UCB). MATERIAL AND METHODS: The PubMed, Web of Science, and Scopus databases were searched in August 2020 according to the PRISMA statement. Studies were deemed eligible if they compared oncologic or pathologic outcomes in patients treated with NAST for UCB with and without detected pretreatment tissue-based biomarkers. RESULTS: Overall, 44 studies met our eligibility criteria. Twenty-three studies used immunohistochemistry (IHC), 19 - gene expression analysis, three - quantitative polymerase chain reaction (QT PCR), and two - next-generation sequencing (NGS). According to the currently available literature, predictive IHC-assessed biomarkers, such as receptor tyrosine kinases and DNA repair pathway alterations, do not seem to convincingly improve our prediction of pathologic response and oncologic outcomes after NAC. Luminal and basal tumor subtypes based on gene expression analysis showed better NAC response, while claudin-low and luminal-infiltrated tumor subtypes did not. In terms of NAI, PD-L1 seems to maintain value as a predictive biomarker, while the utility of both tumor mutational burden and molecular subtypes remains controversial. Specific genomic alterations in DNA repair genes have been shown to provide significant predictive value in patient treated with NAC. QT PCR quantification of specific genes selected through microarray analysis seems to classify cases regarding their NAC response. CONCLUSION: We believe that the present systematic review may offer a robust framework that will enable the testing and validation of predictive biomarkers in future prospective clinical trials. NGS has expanded the discovery of molecular markers that are reflective of the mechanisms of the NAST response.
Authors: Soum D Lokeshwar; Maite Lopez; Semih Sarcan; Karina Aguilar; Daley S Morera; Devin M Shaheen; Bal L Lokeshwar; Vinata B Lokeshwar Journal: Cancers (Basel) Date: 2022-05-24 Impact factor: 6.575
Authors: Maria Skydt Lindgren; Philippe Lamy; Sia Viborg Lindskrog; Emil Christensen; Iver Nordentoft; Karin Birkenkamp-Demtröder; Benedicte Parm Ulhøi; Jørgen Bjerggaard Jensen; Lars Dyrskjøt Journal: Eur Urol Open Sci Date: 2021-11-05
Authors: Line H Dohn; Peter Thind; Lisbeth Salling; Henriette Lindberg; Sofie Oersted; Ib J Christensen; Ole D Laerum; Martin Illemann; Hans von der Maase; Gunilla Høyer-Hansen; Helle Pappot Journal: Cancers (Basel) Date: 2021-05-14 Impact factor: 6.639
Authors: Ekaterina Laukhtina; Victor M Schuettfort; David D'Andrea; Benjamin Pradere; Keiichiro Mori; Fahad Quhal; Reza Sari Motlagh; Hadi Mostafaei; Satoshi Katayama; Nico С Grossmann; Pawel Rajwa; Flora Zeinler; Mohammad Abufaraj; Marco Moschini; Kristin Zimmermann; Pierre I Karakiewicz; Harun Fajkovic; Douglas Scherr; Eva Compérat; Peter Nyirady; Michael Rink; Dmitry Enikeev; Shahrokh F Shariat Journal: Mol Carcinog Date: 2021-09-29 Impact factor: 5.139