{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:57:16Z","timestamp":1792079836796,"version":"4.4.0"},"reference-count":125,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>Bladder cancer grading provides important prognostic information to clinicians, and the assigned grade is used as a variable in risk stratification models. There have been multiple proposed grading schemes over the last century, with the most widely utilized in contemporary practice being the World Health Organization (WHO) 1973 and 2004 schemes, with WHO 2004 used almost exclusively in North America, and dual grading using both 2004 and 1973 is in widespread use in Europe. Recently, there has been increased interest in hybrid grading schemes for papillary bladder cancer. These combine features from both aforementioned schemes and have demonstrated prognostic performance that exceeds WHO 2004 and WHO 1973. In this article, we review the historical background and new concepts in bladder cancer grading, highlight the opinions and perspectives of clinicians and pathologists, and assess the challenges along with evidence for and against different grading schemes. We discuss the potential contribution of hybrid 3\u2010tier grading of bladder cancer and how this could impact the classification of papillary urothelial neoplasms and shape future grading scheme proposals.<\/jats:p>","DOI":"10.1111\/his.15559","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:23:30Z","timestamp":1765545810000},"page":"86-107","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Grading of bladder cancer: updates, controversies and practical solutions"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4528-3724","authenticated-orcid":false,"given":"Michelle R","family":"Downes","sequence":"first","affiliation":[{"name":"Division of Anatomic Pathology, Department of Laboratory Medicine and Molecular Diagnostics, Precision Diagnostics and Therapeutics Program Sunnybrook Health Sciences Centre  Toronto Ontario Canada"},{"name":"Laboratory Medicine and Pathobiology University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8640-5786","authenticated-orcid":false,"given":"Theodorus H","family":"van der Kwast","sequence":"additional","affiliation":[{"name":"Laboratory Medicine Program University Health Network, Princess Margaret Cancer Center, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3161-8164","authenticated-orcid":false,"given":"Antonio","family":"Lopez\u2010Beltran","sequence":"additional","affiliation":[{"name":"Unit of Anatomic Pathology, Department of Morphological Sciences Cordoba University Medical School  Cordoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6049-5293","authenticated-orcid":false,"given":"Liang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Brown University Warren Alpert Medical School, Legorreta Cancer Center at Brown University, and Brown University Health  Rhode Island USA"},{"name":"Department of Surgery (Urology) Brown University Warren Alpert Medical School Legorreta Cancer Center at Brown University, and Brown University Health  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"e_1_2_17_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"e_1_2_17_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-40618-3"},{"key":"e_1_2_17_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2005.07.062"},{"key":"e_1_2_17_5_1","volume-title":"Urinary and male genital tumours. WHO classification of tumours","author":"WHO Classification of Tumours Editorial Board","year":"2022"},{"key":"e_1_2_17_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2012.04.009"},{"key":"e_1_2_17_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2013.05.040"},{"key":"e_1_2_17_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2022.01.008"},{"key":"e_1_2_17_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13752"},{"key":"e_1_2_17_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2017.125"},{"key":"e_1_2_17_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31952"},{"key":"e_1_2_17_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000001325"},{"key":"e_1_2_17_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000002077"},{"key":"e_1_2_17_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000001305"},{"key":"e_1_2_17_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-020-03362-1"},{"key":"e_1_2_17_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/17562872241249073"},{"key":"e_1_2_17_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/23523735251335122"},{"key":"e_1_2_17_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-023-02543-0"},{"key":"e_1_2_17_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/CU9.0000000000000263"},{"key":"e_1_2_17_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2021.09.026"},{"key":"e_1_2_17_21_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2024.0024"},{"key":"e_1_2_17_22_1","article-title":"Lines of therapy for locally advanced\/metastatic urothelial carcinoma: the new paradigm","author":"Abidoye O","year":"2025","journal-title":"JCO Oncol. Pract."},{"key":"e_1_2_17_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2023-076743"},{"key":"e_1_2_17_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001453"},{"key":"e_1_2_17_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2308849"},{"key":"e_1_2_17_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2312117"},{"key":"e_1_2_17_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2025.02.019"},{"key":"e_1_2_17_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000003981"},{"key":"e_1_2_17_29_1","unstructured":"The Surveillance E and End Results (SEER) Program."},{"key":"e_1_2_17_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2012.04.010"},{"key":"e_1_2_17_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e318253d6e0"},{"key":"e_1_2_17_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2010.09515.x"},{"key":"e_1_2_17_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.14238"},{"key":"e_1_2_17_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2019.05.001"},{"key":"e_1_2_17_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.12666"},{"key":"e_1_2_17_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2021.10.005"},{"key":"e_1_2_17_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2020.12.002"},{"key":"e_1_2_17_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2024.08.013"},{"key":"e_1_2_17_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2017.04.015"},{"key":"e_1_2_17_40_1","volume-title":"International histological classification of tumours, no. 10","author":"Mostofi FK","year":"1973"},{"key":"e_1_2_17_41_1","volume-title":"Pathology and genetics of tumours of the urinary system and male genital organs. WHO classification of tumours","author":"Eble JN","year":"2004"},{"key":"e_1_2_17_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-192205000-00002"},{"key":"e_1_2_17_43_1","first-page":"1","article-title":"Tumors of the urinary bladder: a pathological and clinical study of 434 cases","volume":"151","author":"Franksson C","year":"1950","journal-title":"Acta Chir. Scand. Suppl."},{"key":"e_1_2_17_44_1","first-page":"371","article-title":"Classification of bladder tumours based on the cellular pattern. Preliminary report of a clinical\u2010pathological study of 300 cases with a minimum follow\u2010up of eight years","volume":"130","author":"Bergkvist A","year":"1965","journal-title":"Acta Chir. Scand."},{"key":"e_1_2_17_45_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365598709180320"},{"key":"e_1_2_17_46_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199812000-00001"},{"key":"e_1_2_17_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-59871-5"},{"key":"e_1_2_17_48_1","volume-title":"WHO classification of tumours of the urinary system and male genital organs, WHO classification of tumours","author":"Moch H","year":"2016"},{"key":"e_1_2_17_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2012.01.008"},{"key":"e_1_2_17_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euf.2021.03.017"},{"key":"e_1_2_17_51_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000002059"},{"key":"e_1_2_17_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.15438"},{"key":"e_1_2_17_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jasc.2021.12.003"},{"key":"e_1_2_17_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(20000401)88:7<1663::AID-CNCR21>3.0.CO;2-8"},{"key":"e_1_2_17_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2021.07.003"},{"key":"e_1_2_17_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2015.09.007"},{"key":"e_1_2_17_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-014-1383-5"},{"key":"e_1_2_17_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2013.11.056"},{"key":"e_1_2_17_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2025.102357"},{"key":"e_1_2_17_60_1","doi-asserted-by":"crossref","unstructured":"36th European Congress of Pathology\u2013abstracts. Virchows Archiv 2024;485;1\u2013546.","DOI":"10.1007\/s00428-024-03880-y"},{"key":"e_1_2_17_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(06)00267-9"},{"key":"e_1_2_17_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-003-0905-0"},{"key":"e_1_2_17_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-011-1072-3"},{"key":"e_1_2_17_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2019.10.002"},{"key":"e_1_2_17_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-017-2164-5"},{"key":"e_1_2_17_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13441"},{"key":"e_1_2_17_67_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.20003"},{"key":"e_1_2_17_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2020.12.007"},{"key":"e_1_2_17_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)67975-X"},{"key":"e_1_2_17_70_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-410x.1998.00628.x"},{"key":"e_1_2_17_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2005.12.031"},{"key":"e_1_2_17_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/0959-8049(95)00287-S"},{"key":"e_1_2_17_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2021.08.010"},{"key":"e_1_2_17_74_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000003846"},{"key":"e_1_2_17_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2023.01.004"},{"key":"e_1_2_17_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euf.2022.04.014"},{"key":"e_1_2_17_77_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-020-03180-5"},{"key":"e_1_2_17_78_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13000-019-0868-3"},{"key":"e_1_2_17_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2018.05.002"},{"key":"e_1_2_17_80_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0083192"},{"key":"e_1_2_17_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2009.03.052"},{"key":"e_1_2_17_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2009.09.022"},{"key":"e_1_2_17_83_1","doi-asserted-by":"publisher","DOI":"10.1159\/000100839"},{"key":"e_1_2_17_84_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2004.04848.x"},{"key":"e_1_2_17_85_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000055471.78783.ae"},{"key":"e_1_2_17_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)64553-3"},{"key":"e_1_2_17_87_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-410x.2000.00356.x"},{"key":"e_1_2_17_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2025.04.010"},{"key":"e_1_2_17_89_1","unstructured":"EAU Guidelines.Presented at the EAU Annual Congress Madrid 2025. Accessed 18 July 2025.https:\/\/uroweb.org\/guidelines\/non\u2010muscle\u2010invasive\u2010bladder\u2010cancer."},{"key":"e_1_2_17_90_1","unstructured":"VarmaM ShanksJH ChandraA McWilliamL.The Royal College dataset for histopathological reporting of tumours of the urinary collecting system (renal pelvis ureter urinary bladder and urethra).2021."},{"key":"e_1_2_17_91_1","doi-asserted-by":"publisher","DOI":"10.1086\/302063"},{"key":"e_1_2_17_92_1","doi-asserted-by":"publisher","DOI":"10.1080\/21681805.2022.2041086"},{"key":"e_1_2_17_93_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.JU.0001109740.05294.af.19"},{"key":"e_1_2_17_94_1","doi-asserted-by":"publisher","DOI":"10.5858\/2006-130-844-DPOBCP"},{"key":"e_1_2_17_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64665-2"},{"key":"e_1_2_17_96_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000002053"},{"key":"e_1_2_17_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2016.05.014"},{"key":"e_1_2_17_98_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4017"},{"key":"e_1_2_17_99_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13063"},{"key":"e_1_2_17_100_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000004305"},{"key":"e_1_2_17_101_1","doi-asserted-by":"publisher","DOI":"10.1002\/cjp2.245"},{"key":"e_1_2_17_102_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2014.154"},{"key":"e_1_2_17_103_1","first-page":"4658","article-title":"Chromosomal imbalances in noninvasive papillary bladder neoplasms (PTA)","volume":"59","author":"Zhao J","year":"1999","journal-title":"Cancer Res."},{"key":"e_1_2_17_104_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2012.05.063"},{"key":"e_1_2_17_105_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.05.073"},{"key":"e_1_2_17_106_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-4213"},{"key":"e_1_2_17_107_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2017.05.040"},{"key":"e_1_2_17_108_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2020.09.014"},{"key":"e_1_2_17_109_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13734"},{"key":"e_1_2_17_110_1","doi-asserted-by":"publisher","DOI":"10.1016\/0741-5214(91)90060-8"},{"key":"e_1_2_17_111_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejso.2006.04.006"},{"key":"e_1_2_17_112_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19831001)52:7<1273::AID-CNCR2820520724>3.0.CO;2-7"},{"key":"e_1_2_17_113_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2005.05.027"},{"key":"e_1_2_17_114_1","doi-asserted-by":"publisher","DOI":"10.1111\/iju.13261"},{"key":"e_1_2_17_115_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16167"},{"key":"e_1_2_17_116_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2019.06.010"},{"key":"e_1_2_17_117_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAP.0000000000000510"},{"key":"e_1_2_17_118_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000002416"},{"key":"e_1_2_17_119_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAP.0000000000000110"},{"key":"e_1_2_17_120_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/7308168"},{"key":"e_1_2_17_121_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31805c9cd9"},{"key":"e_1_2_17_122_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-004-0457-6"},{"key":"e_1_2_17_123_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-019-6430-6"},{"key":"e_1_2_17_124_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euros.2023.03.019"},{"key":"e_1_2_17_125_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000004542"},{"key":"e_1_2_17_126_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.15091"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.15559","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/his.15559","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.15559","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T21:50:08Z","timestamp":1785448208000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.15559"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,12]]},"references-count":125,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/his.15559"],"URL":"https:\/\/doi.org\/10.1111\/his.15559","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,12]]},"assertion":[{"value":"2025-12-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}