{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:54:38Z","timestamp":1790106878662,"version":"4.0.1"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003107","name":"Bundesministerium f\u00fcr Gesundheit","doi-asserted-by":"publisher","award":["2519DAT712"],"award-info":[{"award-number":["2519DAT712"]}],"id":[{"id":"10.13039\/501100003107","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003107","name":"Bundesministerium f\u00fcr Gesundheit","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003107","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJU International"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To develop a new digital biomarker based on the analysis of primary tumour tissue by a convolutional neural network (CNN) to predict lymph node metastasis (LNM) in a cohort matched for already established risk factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>Haematoxylin and eosin (H&amp;E) stained primary tumour slides from 218 patients (102 N+; 116 N0), matched for Gleason score, tumour size, venous invasion, perineural invasion and age, who underwent radical prostatectomy were selected to train a CNN and evaluate its ability to predict LN status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      With 10 models trained with the same data, a mean area under the receiver operating characteristic curve (AUROC) of 0.68 (95% confidence interval [CI] 0.678\u20130.682) and a mean balanced accuracy of 61.37% (95% CI 60.05\u201362.69%) was achieved. The mean sensitivity and specificity was 53.09% (95% CI 49.77\u201356.41%) and 69.65% (95% CI 68.21\u201371.1%), respectively. These results were confirmed via cross\u2010validation. The probability score for LNM prediction was significantly higher on image sections from N+ samples (mean [SD] N+ probability score 0.58 [0.17] vs 0.47 [0.15] N0 probability score,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.002). In multivariable analysis, the probability score of the CNN (odds ratio [OR] 1.04 per percentage probability, 95% CI 1.02\u20131.08;\n                      <jats:italic>P<\/jats:italic>\n                      = 0.04) and lymphovascular invasion (OR 11.73, 95% CI 3.96\u201335.7;\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001) proved to be independent predictors for LNM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In our present study, CNN\u2010based image analyses showed promising results as a potential novel low\u2010cost method to extract relevant prognostic information directly from H&amp;E histology to predict the LN status of patients with prostate cancer. Our ubiquitously available technique might contribute to an improved LN status prediction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bju.15386","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T18:01:28Z","timestamp":1615485688000},"page":"352-360","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Deep learning approach to predict lymph node metastasis directly from primary tumour histology in prostate cancer"],"prefix":"10.1111","volume":"128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4213-8692","authenticated-orcid":false,"given":"Frederik","family":"Wessels","sequence":"first","affiliation":[{"name":"Digital Biomarkers for Oncology Group National Center for Tumor Diseases (NCT) German Cancer Research Center (DKFZ) Heidelberg Germany"},{"name":"Department of Urology and Urological Surgery Medical Faculty Mannheim of Heidelberg University University Medical Center Mannheim Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Digital Biomarkers for Oncology Group National Center for Tumor Diseases (NCT) German Cancer Research Center (DKFZ) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Krieghoff\u2010Henning","sequence":"additional","affiliation":[{"name":"Digital Biomarkers for Oncology Group National Center for Tumor Diseases (NCT) German Cancer Research Center (DKFZ) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Jutzi","sequence":"additional","affiliation":[{"name":"Digital Biomarkers for Oncology Group National Center for Tumor Diseases (NCT) German Cancer Research Center (DKFZ) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Worst","sequence":"additional","affiliation":[{"name":"Department of Urology and Urological Surgery Medical Faculty Mannheim of Heidelberg University University Medical Center Mannheim Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Waldbillig","sequence":"additional","affiliation":[{"name":"Department of Urology and Urological Surgery Medical Faculty Mannheim of Heidelberg University University Medical Center Mannheim Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Neuberger","sequence":"additional","affiliation":[{"name":"Department of Urology and Urological Surgery Medical Faculty Mannheim of Heidelberg University University Medical Center Mannheim Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman C.","family":"Maron","sequence":"additional","affiliation":[{"name":"Digital Biomarkers for Oncology Group National Center for Tumor Diseases (NCT) German Cancer Research Center (DKFZ) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Steeg","sequence":"additional","affiliation":[{"name":"Institute of Pathology Medical Faculty Mannheim of Heidelberg University University Medical Center Mannheim Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Gaiser","sequence":"additional","affiliation":[{"name":"Institute of Pathology Medical Faculty Mannheim of Heidelberg University University Medical Center Mannheim Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Hekler","sequence":"additional","affiliation":[{"name":"Digital Biomarkers for Oncology Group National Center for Tumor Diseases (NCT) German Cancer Research Center (DKFZ) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen S.","family":"Utikal","sequence":"additional","affiliation":[{"name":"Skin Cancer Unit German Cancer Research Center (DKFZ) Heidelberg Germany"},{"name":"Department of Dermatology, Venereology and Allergology University Medical Center Mannheim University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof","family":"von Kalle","sequence":"additional","affiliation":[{"name":"Department of Clinical\u2010Translational Sciences Berlin Institute of Health (BIH) Charit\u00e9 University Medicine Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Fr\u00f6hling","sequence":"additional","affiliation":[{"name":"National Center for Tumor Diseases German Cancer Research Center Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurice S.","family":"Michel","sequence":"additional","affiliation":[{"name":"Department of Urology and Urological Surgery Medical Faculty Mannheim of Heidelberg University University Medical Center Mannheim Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Nuhn","sequence":"additional","affiliation":[{"name":"Department of Urology and Urological Surgery Medical Faculty Mannheim of Heidelberg University University Medical Center Mannheim Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3620-5919","authenticated-orcid":false,"given":"Titus J.","family":"Brinker","sequence":"additional","affiliation":[{"name":"Digital Biomarkers for Oncology Group National Center for Tumor Diseases (NCT) German Cancer Research Center (DKFZ) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2018.07.005"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2008.09.043"},{"key":"e_1_2_9_4_1","unstructured":"EAU Guidelines.Edn. presented at the EAU Annual Congress Amsterdam 2020. ISBN 978\u201094\u201092671\u201007\u20103"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2018.10.012"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2011.10.044"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.15220"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2020.03.023"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2020.09.042"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2016.12.003"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2020.11.002"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2019.04.001"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2019.06.012"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep26286"},{"key":"e_1_2_9_15_1","article-title":"Development of a deep learning algorithm for the histopathologic diagnosis and gleason grading of prostate cancer biopsies: a pilot study","author":"Kott O","year":"2019","journal-title":"Eur Urol Focus."},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2009.10.046"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30739-9"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1109\/TCBB.2019.2941195"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-020-0087-6"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-020-0085-8"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13647-8"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5"},{"key":"e_1_2_9_23_1","unstructured":"LoshchilovI HutterF.SGDR: Stochastic gradient descent with warm restarts 2016"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/info11020108"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neucom.2019.01.103"},{"key":"e_1_2_9_26_1","unstructured":"PaszkeA GrossS MassaF editorset\u00a0al.Pytorch: an imperative style high\u2010performance deep learning library. Advances in neural information processing systems 2019"},{"key":"e_1_2_9_27_1","unstructured":"Memorial Sloan\u2010Kettering Cancer Center. Prediction Tools\/Prostate Cancer Nomograms. Available at:https:\/\/www.mskcc.org\/nomograms\/prostate\/pre_op. Accessed January 2021"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/19336918.2016.1182292"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6029"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2011.01.006"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.43.1882"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-12-0085"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20288"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700181"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-35501-5"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kjms.2011.10.007"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2017.167"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2013.02.007"}],"container-title":["BJU International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bju.15386","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bju.15386","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bjui-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bju.15386","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T13:10:54Z","timestamp":1761743454000},"score":1,"resource":{"primary":{"URL":"https:\/\/bjui-journals.onlinelibrary.wiley.com\/doi\/10.1111\/bju.15386"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,5]]},"references-count":37,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["10.1111\/bju.15386"],"URL":"https:\/\/doi.org\/10.1111\/bju.15386","archive":["Portico"],"relation":{},"ISSN":["1464-4096","1464-410X"],"issn-type":[{"value":"1464-4096","type":"print"},{"value":"1464-410X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,5]]},"assertion":[{"value":"2021-05-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}