{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:11:57Z","timestamp":1791911517611,"version":"4.3.4"},"reference-count":22,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","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":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To retrospectively analyse the results of the Prostate Testing for Cancer and Treatment (ProtecT; ClinicalTrials.gov identifier: NCT02044172) trial to establish the association between cribriform\u2010positive and \u2010negative prostate cancer (PCa) and the 15\u2010year risk of metastasis or death from PCa in patients who underwent radical prostatectomy (RP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>Between 1999 and 2009, the ProtecT phase 3 clinical trial enrolled 1643 men with clinically localised PCa who were randomised to receive active monitoring, RP, or radiotherapy. In this secondary analysis of the trial, a centralised histopathological review was conducted on available RP pathology slides to classify patients as cribriform\u2010positive if they had invasive cribriform carcinoma and\/or intraductal carcinoma. The primary outcome was a composite of progression to metastatic disease or death from PCa. Exposures included age, prostate\u2010specific antigen density, RP Grade Group (GG), pathological T stage (pT), and cribriform status. Multivariable Cox proportional hazards regression models assessed 15\u2010year risk. Cumulative incidence curves were compared using the Gray test.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 480 men with RP specimens reviewed, 143 (30%) had cribriform\u2010positive disease and 337 (70%) had cribriform\u2010negative disease. All 21 metastatic or lethal events occurred exclusively in the cribriform\u2010positive group (15\u2010year cumulative incidence 14%). Within the cribriform\u2010positive cohort, risk was concentrated in patients with pT3b stage and\/or GG \u22653 (15\u2010year cumulative incidence 27%). In multivariable analysis of cribriform\u2010positive patients, pT3b stage (hazard ratio [HR] 8.19, 95% confidence interval [CI] 2.39\u201328.10;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001) and GG 3 disease (HR 5.12, 95% CI 1.59\u201316.40;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.006) were independent predictors of adverse outcomes. Conversely, cribriform\u2010positive patients with GG 2 and \u2264pT3a had a 15\u2010year event rate of only 3%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In the ProtecT trial, the 15\u2010year risk of metastasis or death after RP was a binary outcome defined by cribriform status. The concentration of risk in men with cribriform\u2010positive, high\u2010grade and\/or pT3b tumours identifies a target population for adjuvant therapy trials, while supporting management de\u2010escalation for most RP patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bju.70261","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T04:23:41Z","timestamp":1774671821000},"page":"984-991","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Long\u2010term outcomes of cribriform\u2010positive and cribriform\u2010negative prostate cancer treated with radical prostatectomy in the\n                    <scp>ProtecT<\/scp>\n                    trial"],"prefix":"10.1111","volume":"137","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4500-9714","authenticated-orcid":false,"given":"Nikita","family":"Sushentsev","sequence":"first","affiliation":[{"name":"Department of Radiology University of Cambridge  Cambridge UK"},{"name":"Nuffield Department of Surgical Sciences University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Y.","family":"Warren","sequence":"additional","affiliation":[{"name":"Department of Pathology Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Colling","sequence":"additional","affiliation":[{"name":"Nuffield Department of Surgical Sciences University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"Verrill","sequence":"additional","affiliation":[{"name":"Nuffield Department of Surgical Sciences University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Pazukhina","sequence":"additional","affiliation":[{"name":"Wolfson Institute of Population Health Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Blyuss","sequence":"additional","affiliation":[{"name":"Wolfson Institute of Population Health Queen Mary University of London  London UK"},{"name":"Department of Pediatrics and Pediatric Infectious Diseases Institute of Child's Health, Sechenov University  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Zaikin","sequence":"additional","affiliation":[{"name":"Department of Women's Cancer, Institute for Women's Health University College London  London UK"},{"name":"Department of Mathematics University College London  London UK"},{"name":"Institute for Cognitive Neuroscience National Research University Higher School of Economics  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler M.","family":"Seibert","sequence":"additional","affiliation":[{"name":"Department of Radiation Medicine and Applied Sciences University of California San Diego  San Diego CA USA"},{"name":"Department of Urology University of California San Diego  La Jolla CA USA"},{"name":"Department of Bioengineering University of California San Diego Jacobs School of Engineering  La Jolla CA USA"},{"name":"Department of Radiology University of California San Diego School of Medicine  La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tristan","family":"Barrett","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4348-0273","authenticated-orcid":false,"given":"Jon","family":"Oxley","sequence":"additional","affiliation":[{"name":"Department of Histopathology North Bristol Hospitals Trust  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian G.","family":"Mills","sequence":"additional","affiliation":[{"name":"Nuffield Department of Surgical Sciences University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8330-9251","authenticated-orcid":false,"given":"Richard J.","family":"Bryant","sequence":"additional","affiliation":[{"name":"Nuffield Department of Surgical Sciences University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7578-4925","authenticated-orcid":false,"given":"J. 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