{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:36:06Z","timestamp":1791606966824,"version":"4.3.4"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T00:00:00Z","timestamp":1644796800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T00:00:00Z","timestamp":1644796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Percentage Gleason pattern 4, invasive cribriform and\/or intraductal carcinoma (IC\/IDC) and minor pattern 5 are recognized as independent parameters for prostate cancer outcome, but are not incorporated in current grade groups (GGs). Two proof-of-principle studies have proposed alternative grading schemes based on percentage Gleason pattern 4\/5 (integrated quantitative Gleason score; IQ-Gleason) and IC\/IDC presence (cribriform grade; cGrade). Our objective was to compare the performance of GG, IQ-Gleason and cGrade for predicting biochemical recurrence and metastasis after radical prostatectomy (RP). RP specimens of 1064 patients were pathologically reviewed and graded according to the three schemes. Discriminative power for prediction of biochemical recurrence-free (BCRFS) and metastasis-free (MFS) survival was compared using Harrell\u2019s\n                    <jats:italic>c<\/jats:italic>\n                    -index. The GG distribution at RP was 207 (19.4%) GG1, 472 (44.4%) GG2, 126 (11.8%) GG3, 140 (13.2%) GG4 and 119 (11.2%) GG5. Grading according to 5-tier IQ-Gleason and cGrade systems led to categorical shifts in 49.8% and 29.7% of cases, respectively. Continuous IQ-Gleason had the best performance for predicting BCRFS (\n                    <jats:italic>c<\/jats:italic>\n                    -index 0.743, 95% confidence interval (\n                    <jats:italic>CI<\/jats:italic>\n                    ) 0.715\u20130.771), followed by cGrade (\n                    <jats:italic>c<\/jats:italic>\n                    -index 0.738, 95%\n                    <jats:italic>CI<\/jats:italic>\n                    0.712\u20130.759), 5-tier categorical IQ-Gleason (\n                    <jats:italic>c<\/jats:italic>\n                    -index 0.723, 95%\n                    <jats:italic>CI<\/jats:italic>\n                    0.695\u20130.750) and GG (\n                    <jats:italic>c<\/jats:italic>\n                    -index 0.718, 95%\n                    <jats:italic>CI<\/jats:italic>\n                    0.691\u20130.744). Continuous IQ-Gleason (\n                    <jats:italic>c<\/jats:italic>\n                    -index 0.834, 95%\n                    <jats:italic>CI<\/jats:italic>\n                    0.802\u20130.863) and cGrade (\n                    <jats:italic>c<\/jats:italic>\n                    -index 0.834, 95%\n                    <jats:italic>CI<\/jats:italic>\n                    0.808\u20130.866) both had better predictive value for MFS than categorical IQ-Gleason (\n                    <jats:italic>c<\/jats:italic>\n                    -index 0.823, 95%\n                    <jats:italic>CI<\/jats:italic>\n                    0.788\u20130.857) and GG (\n                    <jats:italic>c<\/jats:italic>\n                    -index 0.806, 95%\n                    <jats:italic>CI<\/jats:italic>\n                    0.777\u20130.839). In conclusion, the performance of prostate cancer grading can be improved by alternative grading schemes incorporating percent Gleason pattern 4\/5 and IC\/IDC.\n                  <\/jats:p>","DOI":"10.1007\/s00428-022-03301-y","type":"journal-article","created":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T04:02:47Z","timestamp":1644811367000},"page":"1149-1157","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Alternative prostate cancer grading systems incorporating percent pattern 4\/5 (IQ-Gleason) and cribriform architecture (cGrade) improve prediction of outcome after radical prostatectomy"],"prefix":"10.1007","volume":"480","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5998-8813","authenticated-orcid":false,"given":"Neslisah","family":"Seyrek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Hollemans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni-Rosalina","family":"Andrinopoulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Osanto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob C. M.","family":"Pelger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk G.","family":"van der Poel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Bekers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiaan","family":"Remmers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo G.","family":"Schoots","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert J. L. H.","family":"van Leenders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,2,14]]},"reference":[{"key":"3301_CR1","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.humpath.2016.12.008","volume":"63","author":"AS Baras","year":"2017","unstructured":"Baras AS, Nelson JB, Han M, Parwani AV, Epstein JI (2017) The effect of limited (tertiary) Gleason pattern 5 on the new prostate cancer grade groups. Hum Pathol 63:27\u201332. https:\/\/doi.org\/10.1016\/j.humpath.2016.12.008","journal-title":"Hum Pathol"},{"key":"3301_CR2","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1097\/pas.0000000000000691","volume":"40","author":"B Choy","year":"2016","unstructured":"Choy B, Pearce SM, Anderson BB, Shalhav AL, Zagaja G, Eggener SE, Paner GP (2016) Prognostic significance of percentage and architectural types of contemporary Gleason pattern 4 prostate cancer in radical prostatectomy. Am J Surg Pathol 40:1400\u20131406. https:\/\/doi.org\/10.1097\/pas.0000000000000691","journal-title":"Am J Surg Pathol"},{"key":"3301_CR3","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1111\/his.13938","volume":"75","author":"MR Downes","year":"2019","unstructured":"Downes MR, Xu B, van der Kwast TH (2019) Gleason grade patterns in nodal metastasis and corresponding prostatectomy specimens: impact on patient outcome. Histopathology 75:715\u2013722. https:\/\/doi.org\/10.1111\/his.13938","journal-title":"Histopathology"},{"key":"3301_CR4","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2020-0015-RA","author":"JI Epstein","year":"2020","unstructured":"Epstein JI, Amin MB, Fine SW, Algaba F, Aron M, Baydar DE, Beltran AL, Brimo F, Cheville JC, Colecchia M, Comperat E, da Cunha IW, Delprado W, DeMarzo AM, Giannico GA, Gordetsky JB, Guo CC, Hansel DE, Hirsch MS, Huang J, Humphrey PA, Jimenez RE, Khani F, Kong Q, Kryvenko ON, Kunju LP, Lal P, Latour M, Lotan T, Maclean F, Magi-Galluzzi C, Mehra R, Menon S, Miyamoto H, Montironi R, Netto GJ, Nguyen JK, Osunkoya AO, Parwani A, Robinson BD, Rubin MA, Shah RB, So JS, Takahashi H, Tavora F, Tretiakova MS, True L, Wobker SE, Yang XJ, Zhou M, Zynger DL, Trpkov K (2020) The 2019 Genitourinary Pathology Society (GUPS) white paper on contemporary grading of prostate cancer. Arch Pathol Lab Med. https:\/\/doi.org\/10.5858\/arpa.2020-0015-RA","journal-title":"Arch Pathol Lab Med"},{"key":"3301_CR5","doi-asserted-by":"publisher","unstructured":"Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA, Grading C (2016) The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: definition of grading patterns and proposal for a new grading system. Am J Surg Pathol 40:244\u2013252. https:\/\/doi.org\/10.1097\/PAS.0000000000000530","DOI":"10.1097\/PAS.0000000000000530"},{"key":"3301_CR6","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1016\/j.eururo.2015.06.046","volume":"69","author":"JI Epstein","year":"2016","unstructured":"Epstein JI, Zelefsky MJ, Sjoberg DD, Nelson JB, Egevad L, Magi-Galluzzi C, Vickers AJ, Parwani AV, Reuter VE, Fine SW, Eastham JA, Wiklund P, Han M, Reddy CA, Ciezki JP, Nyberg T, Klein EA (2016) A contemporary prostate cancer grading system: a validated alternative to the Gleason score. Eur Urol 69:428\u2013435. https:\/\/doi.org\/10.1016\/j.eururo.2015.06.046","journal-title":"Eur Urol"},{"key":"3301_CR7","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1007\/s00428-017-2241-9","volume":"472","author":"TA Flood","year":"2018","unstructured":"Flood TA, Schieda N, Sim J, Breau RH, Morash C, Belanger EC, Robertson SJ (2018) Evaluation of tumor morphologies and association with biochemical recurrence after radical prostatectomy in grade group 5 prostate cancer. Virchows Arch 472:205\u2013212. https:\/\/doi.org\/10.1007\/s00428-017-2241-9","journal-title":"Virchows Arch"},{"key":"3301_CR8","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1016\/j.juro.2016.05.105","volume":"196","author":"N Harding-Jackson","year":"2016","unstructured":"Harding-Jackson N, Kryvenko ON, Whittington EE, Eastwood DC, Tjionas GA, Jorda M, Iczkowski KA (2016) Outcome of Gleason 3 + 5 = 8 prostate cancer diagnosed on needle biopsy: prognostic comparison with Gleason 4 + 4 = 8. J Urol 196:1076\u20131081. https:\/\/doi.org\/10.1016\/j.juro.2016.05.105","journal-title":"J Urol"},{"key":"3301_CR9","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.eururo.2016.02.028","volume":"70","author":"PA Humphrey","year":"2016","unstructured":"Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE (2016) The 2016 WHO classification of tumours of the urinary system and male genital organs\u2014part B: prostate and bladder tumours. Eur Urol 70:106\u2013119. https:\/\/doi.org\/10.1016\/j.eururo.2016.02.028","journal-title":"Eur Urol"},{"key":"3301_CR10","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1038\/s41379-018-0121-8","volume":"32","author":"M Kato","year":"2019","unstructured":"Kato M, Hirakawa A, Kobayashi Y, Yamamoto A, Ishida R, Kamihira O, Kimura T, Majima T, Ishida S, Funahashi Y, Sassa N, Fujita T, Matsukawa Y, Yamamoto T, Hattori R, Gotoh M, Tsuzuki T (2019) Integrating tertiary Gleason pattern 5 into the ISUP grading system improves prediction of biochemical recurrence in radical prostatectomy patients. Mod Pathol 32:122\u2013127. https:\/\/doi.org\/10.1038\/s41379-018-0121-8","journal-title":"Mod Pathol"},{"key":"3301_CR11","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1038\/modpathol.2017.29","volume":"30","author":"CF Kweldam","year":"2017","unstructured":"Kweldam CF, Kummerlin IP, Nieboer D, Steyerberg EW, Bangma CH, Incrocci L, van der Kwast TH, Roobol MJ, van Leenders GJ (2017) Presence of invasive cribriform or intraductal growth at biopsy outperforms percentage grade 4 in predicting outcome of Gleason score 3+4=7 prostate cancer. Mod Pathol 30:1126\u20131132. https:\/\/doi.org\/10.1038\/modpathol.2017.29","journal-title":"Mod Pathol"},{"key":"3301_CR12","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/modpathol.2014.116","volume":"28","author":"CF Kweldam","year":"2015","unstructured":"Kweldam CF, Wildhagen MF, Steyerberg EW, Bangma CH, van der Kwast TH, van Leenders GJ (2015) Cribriform growth is highly predictive for postoperative metastasis and disease-specific death in Gleason score 7 prostate cancer. Mod Pathol 28:457\u2013464. https:\/\/doi.org\/10.1038\/modpathol.2014.116","journal-title":"Mod Pathol"},{"key":"3301_CR13","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1111\/j.1464-410X.2012.11611.x","volume":"111","author":"PM Pierorazio","year":"2013","unstructured":"Pierorazio PM, Walsh PC, Partin AW, Epstein JI (2013) Prognostic Gleason grade grouping: data based on the modified Gleason scoring system. BJU Int 111:753\u2013760. https:\/\/doi.org\/10.1111\/j.1464-410X.2012.11611.x","journal-title":"BJU Int"},{"key":"3301_CR14","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1016\/j.eururo.2017.01.015","volume":"73","author":"G Sauter","year":"2018","unstructured":"Sauter G, Clauditz T, Steurer S, Wittmer C, B\u00fcscheck F, Krech T, Lutz F, Lennartz M, Harms L, Lawrenz L, M\u00f6ller-Koop C, Simon R, Jacobsen F, Wilczak W, Minner S, Tsourlakis MC, Chirico V, Weidemann S, Haese A, Steuber T, Salomon G, Matiu M, Vettorazzi E, Michl U, Bud\u00e4us L, Tilki D, Thederan I, Pehrke D, Beyer B, Fraune C, G\u00f6bel C, Heinrich M, Juhnke M, M\u00f6ller K, Bawahab AAA, Uhlig R, Huland H, Heinzer H, Graefen M, Schlomm T (2018) Integrating tertiary Gleason 5 patterns into quantitative Gleason grading in prostate biopsies and prostatectomy specimens. Eur Urol 73:674\u2013683. https:\/\/doi.org\/10.1016\/j.eururo.2017.01.015","journal-title":"Eur Urol"},{"key":"3301_CR15","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.eururo.2015.10.029","volume":"69","author":"G Sauter","year":"2016","unstructured":"Sauter G, Steurer S, Clauditz TS, Krech T, Wittmer C, Lutz F, Lennartz M, Janssen T, Hakimi N, Simon R, von Petersdorff-Campen M, Jacobsen F, von Loga K, Wilczak W, Minner S, Tsourlakis MC, Chirico V, Haese A, Heinzer H, Beyer B, Graefen M, Michl U, Salomon G, Steuber T, Budaus LH, Hekeler E, Malsy-Mink J, Kutzera S, Fraune C, Gobel C, Huland H, Schlomm T (2016) Clinical utility of quantitative Gleason grading in prostate biopsies and prostatectomy specimens. Eur Urol 69:592\u2013598. https:\/\/doi.org\/10.1016\/j.eururo.2015.10.029","journal-title":"Eur Urol"},{"key":"3301_CR16","doi-asserted-by":"publisher","DOI":"10.1111\/his.14590","author":"N Seyrek","year":"2021","unstructured":"Seyrek N, Hollemans E, Osanto S, Pelger RCM, van der Poel HG, Bekers E, Bangma CH, Rietbergen J, Roobol MJ, Schoots IG, van Leenders G (2021) Cribriform architecture outperforms percent Gleason pattern 4 and tertiary pattern 5 in predicting outcome of Grade group 2 prostate cancer patients. Histopathology. https:\/\/doi.org\/10.1111\/his.14590","journal-title":"Histopathology"},{"key":"3301_CR17","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1186\/s12885-020-06880-8","volume":"20","author":"S Taguchi","year":"2020","unstructured":"Taguchi S, Uemura Y, Fujimura T, Morikawa T, Naito A, Kawai T, Suzuki M, Kume H, Fukuhara H (2020) Quantification of the individual risk of each Gleason pattern, including tertiary Gleason pattern 5, after radical prostatectomy: development of the modified Gleason grade grouping (mGGG) model. BMC Cancer 20:371. https:\/\/doi.org\/10.1186\/s12885-020-06880-8","journal-title":"BMC Cancer"},{"key":"3301_CR18","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.eururo.2019.07.051","volume":"77","author":"G van Leenders","year":"2020","unstructured":"van Leenders G, Kweldam CF, Hollemans E, K\u00fcmmerlin IP, Nieboer D, Verhoef EI, Remmers S, Incrocci L, Bangma CH, van der Kwast TH, Roobol MJ (2020) Improved prostate cancer biopsy grading by incorporation of invasive cribriform and intraductal carcinoma in the 2014 grade groups. Eur Urol 77:191\u2013198. https:\/\/doi.org\/10.1016\/j.eururo.2019.07.051","journal-title":"Eur Urol"},{"key":"3301_CR19","doi-asserted-by":"publisher","unstructured":"van Leenders G, van der Kwast TH, Grignon DJ, Evans AJ, Kristiansen G, Kweldam CF, Litjens G, McKenney JK, Melamed J, Mottet N, Paner GP, Samaratunga H, Schoots IG, Simko JP, Tsuzuki T, Varma M, Warren AY, Wheeler TM, Williamson SR, Iczkowski KA (2020) The 2019 International Society of Urological Pathology (ISUP) Consensus Conference on Grading of Prostatic Carcinoma. Am J Surg Pathol 44:e87-e99. https:\/\/doi.org\/10.1097\/pas.0000000000001497","DOI":"10.1097\/pas.0000000000001497"}],"container-title":["Virchows Archiv"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-022-03301-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00428-022-03301-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-022-03301-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:31:21Z","timestamp":1654821081000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00428-022-03301-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,14]]},"references-count":19,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["3301"],"URL":"https:\/\/doi.org\/10.1007\/s00428-022-03301-y","relation":{},"ISSN":["0945-6317","1432-2307"],"issn-type":[{"value":"0945-6317","type":"print"},{"value":"1432-2307","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,14]]},"assertion":[{"value":"30 December 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 February 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 February 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 February 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The manuscript contains original unpublished work and is not being submitted for publication elsewhere. All authors agree with the results presented as well as the final draft of the manuscript. The institutional Medical Research Ethics Committee approved this study (MEC-2018\u20131614).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}