{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T18:49:26Z","timestamp":1766515766386,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Movember Foundation (Australia)","award":["\u201cGAP3\u201d"],"award-info":[{"award-number":["\u201cGAP3\u201d"]}]},{"name":"Fondazione IRCCS Istituto Nazionale dei Tumori (Milan, Italy)","award":["\u201cGAP3\u201d"],"award-info":[{"award-number":["\u201cGAP3\u201d"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Little is known about the consequences of delaying radical prostatectomy (RP) after Active Surveillance (AS) according to stringent or wider entry criteria. We investigated the association between inclusion criteria and rates, and timing of adverse pathological findings (APFs) among patients in GAP3 cohorts. Methods: APFs (GG \u2265 3, pT \u2265 3, pN &gt; 0 and positive surgical margins [R1]) were accounted for in very low-risk (VLR: grade group [GG] 1, cT1, positive cores &lt; 3, PSA &lt; 10 ng\/mL, PSA density [PSAD] &lt; 0.15 ng\/mL\/cm3) and low-risk (LR: GG1, cT1-2, PSA \u2264 10 ng\/mL) patients undergoing subsequent RP. The Kaplan\u2013Meier method and log\u2013rank test analyzed APF-free survival. Stratified mixed effects models analyzed association. Results: Out of 21,169 patients on AS, 1742 (VLR: 721; LR: 1021) underwent delayed RP. Most (60.8%) did not have APFs. APFs occurred more frequently (44.6% vs. 31.7%; OR 1.54, p &lt; 0.001) and earlier (median time: 40.3 vs. 62.6 months; p &lt; 0.001) in LR patients, and consisted of pT \u2265 3 (OR 1.47, p = 0.013) or R1 (OR 1.80, p &lt; 0.001), but not of GG \u2265 3 or node involvement. Age (OR 1.05, p &lt; 0.001), PSAD (OR 23.21, p = 0.003), and number of positive cores (OR 1.16, p = 0.004) were independently associated with APFs. Conclusions: AS stands as a safe option for low-risk patients, and most do not have APFs at surgery. Wider entry criteria are associated with pT3 and R1. The prognostic implications remain uncertain.<\/jats:p>","DOI":"10.3390\/cancers14153558","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T03:58:44Z","timestamp":1658462324000},"page":"3558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Adverse Pathological Findings at Radical Prostatectomy following Active Surveillance: Results from the Movember GAP3 Cohort"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6867-7646","authenticated-orcid":false,"given":"Cristina","family":"Marenghi","sequence":"first","affiliation":[{"name":"Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuyu","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA"},{"name":"Department of Urology, University of California Los Angeles, Los Angeles, CA 90095, USA"},{"name":"Jonsson Comprehensive Cancer Centre, University of California Los Angeles, Los Angeles, CA 90095, USA"},{"name":"Institute for Precision Health, University of California Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jozien","family":"Helleman","sequence":"additional","affiliation":[{"name":"Department of Urology, Erasmus MC Cancer Institute, University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daan","family":"Nieboer","sequence":"additional","affiliation":[{"name":"Department of Urology, Erasmus MC Cancer Institute, University Medical Center, 3015 GD Rotterdam, The Netherlands"},{"name":"Department of Public Health, Erasmus MC Cancer Institute, University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e8","family":"Rubio-Briones","sequence":"additional","affiliation":[{"name":"Department of Urology, Hospital VITHAS 9 de Octubre, 46025 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter R.","family":"Carroll","sequence":"additional","affiliation":[{"name":"Department of Urology, University of California, San Francisco, CA 94158, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8208-0635","authenticated-orcid":false,"given":"Lui Shiong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Urology, Sengkang General Hospital and Singapore General Hospital, Singapore 544886, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Valdagni","sequence":"additional","affiliation":[{"name":"Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy"},{"name":"Department of Oncology and Hemato-Oncology, Universit\u00e0 Degli Studi di Milano, 20132 Milan, Italy"},{"name":"Department of Radiation Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0553-7520","authenticated-orcid":false,"given":"Paul C.","family":"Boutros","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA"},{"name":"Department of Urology, University of California Los Angeles, Los Angeles, CA 90095, USA"},{"name":"Jonsson Comprehensive Cancer Centre, University of California Los Angeles, Los Angeles, CA 90095, USA"},{"name":"Institute for Precision Health, University of California Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Nicolai","sequence":"additional","affiliation":[{"name":"Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of Movember Foundation\u2019s Global Action Plan Prostate Cancer Active Surveillance (GAP3) Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1001\/jama.293.17.2095","article-title":"20-Year Outcomes Following Conservative Management of Clinically Localized Prostate Cancer","volume":"293","author":"Albertsen","year":"2005","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.eururo.2017.06.035","article-title":"Quality of Life Outcomes after Primary Treatment for Clinically Localised Prostate Cancer: A Systematic Review","volume":"72","author":"Lardas","year":"2017","journal-title":"Eur. Urol."},{"key":"ref_4","first-page":"CD006590","article-title":"Radical prostatectomy versus deferred treatment for localised prostate cancer","volume":"6","author":"Vernooij","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1056\/NEJMoa1807801","article-title":"Radical Prostatectomy or Watchful Waiting in Prostate Cancer\u201429-Year Follow-up","volume":"379","author":"Holmberg","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.eururo.2020.02.009","article-title":"Radical Prostatectomy or Observation for Clinically Localized Prostate Cancer: Extended Follow-up of the Prostate Cancer Intervention Versus Observation Trial (PIVOT)","volume":"77","author":"Wilt","year":"2020","journal-title":"Eur. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1056\/NEJMoa1606220","article-title":"10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer","volume":"375","author":"Hamdy","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_8","unstructured":"(2021, February 11). PRIAS (Prostate Cancer Research International: Active Surveillance) Website. Available online: www.prias-project.org."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1200\/JCO.2014.55.1192","article-title":"Long-Term Follow-Up of a Large Active Surveillance Cohort of Patients With Prostate Cancer","volume":"33","author":"Klotz","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3379","DOI":"10.1200\/JCO.2015.62.5764","article-title":"Intermediate and Longer-Term Outcomes From a Prospective Active-Surveillance Program for Favorable-Risk Prostate Cancer","volume":"33","author":"Tosoian","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1007\/s00345-020-03471-x","article-title":"Long-term outcomes of active surveillance for clinically localized prostate cancer in a community-based setting: Results from a prospective non-interventional study","volume":"39","author":"Herden","year":"2020","journal-title":"World J. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.eururo.2016.03.048","article-title":"Long-term Results of Active Surveillance in the G\u00f6teborg Randomized, Population-based Prostate Cancer Screening Trial","volume":"70","author":"Godtman","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1464-410X.2011.10707.x","article-title":"Pathological stage distribution in patients treated with radical prostatectomy reflecting the need for protocol-based active surveillance: Results from a contemporary European patient cohort","volume":"110","author":"Seiler","year":"2011","journal-title":"Br. J. Urol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.juro.2013.09.034","article-title":"Population Based Study of Predictors of Adverse Pathology among Candidates for Active Surveillance with Gleason 6 Prostate Cancer","volume":"191","author":"Vellekoop","year":"2014","journal-title":"J. Urol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.eururo.2014.10.010","article-title":"Active Surveillance for Prostate Cancer: A Systematic Review of Clinicopathologic Variables and Biomarkers for Risk Stratification","volume":"67","author":"Loeb","year":"2014","journal-title":"Eur. Urol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1590\/s1677-5538.ibju.2017.0320","article-title":"Clinical and pathologic factors predicting reclassification in active surveillance cohorts","volume":"44","author":"Sierra","year":"2018","journal-title":"Int. Braz. J. Urol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.juro.2018.08.023","article-title":"Older Age Predicts Biopsy and Radical Prostatectomy Grade Reclassification to Aggressive Prostate Cancer in Men on Active Surveillance","volume":"201","author":"Druskin","year":"2018","journal-title":"J. Urol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"E335","DOI":"10.5489\/cuaj.6868","article-title":"Upgrading on radical prostatectomy specimens of very low- and low-risk prostate cancer patients on active surveillance: A population-level analysis","volume":"15","author":"Sayyid","year":"2020","journal-title":"Can. Urol. Assoc. J."},{"key":"ref_19","first-page":"431","article-title":"Prostatectomy pathology findings in an active sur-veillance population","volume":"67","author":"Iborra","year":"2014","journal-title":"Arch. Espa\u00f1oles Urol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/j.urology.2015.07.039","article-title":"Predictors of Adverse Pathology in Men Undergoing Radical Prostatectomy Following Initial Active Surveillance","volume":"86","author":"Reese","year":"2015","journal-title":"Urology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.juro.2015.02.015","article-title":"Incidence and Predictors of Upgrading and Up Staging among 10,000 Contemporary Patients with Low Risk Prostate Cancer","volume":"194","author":"Dinh","year":"2015","journal-title":"J. Urol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1016\/j.juro.2010.06.008","article-title":"Outcome of Primary Versus Deferred Radical Prostatectomy in the National Prostate Cancer Register of Sweden Follow-Up Study","volume":"184","author":"Holmberg","year":"2010","journal-title":"J. Urol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/S0140-6736(16)32401-1","article-title":"Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): A paired validating confirmatory study","volume":"389","author":"Ahmed","year":"2017","journal-title":"Lancet"},{"key":"ref_24","first-page":"729.e1","article-title":"Risk of adverse pathology at prostatectomy in the era of MRI and targeted biopsies; rethinking active surveillance for intermediate risk prostate cancer patients","volume":"39","author":"Bloom","year":"2021","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1148\/radiol.2018181278","article-title":"A Grading System for the Assessment of Risk of Extraprostatic Extension of Prostate Cancer at Multiparametric MRI","volume":"290","author":"Mehralivand","year":"2019","journal-title":"Radiology"},{"key":"ref_26","first-page":"1797","article-title":"Predictors of adverse pathology on radical prostatectomy specimen in men initially enrolled in active surveillance for low-risk prostate cancer","volume":"39","author":"Olsson","year":"2020","journal-title":"World J. Urol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Saoud, R., Heidar, N.A., Cimadamore, A., and Paner, G.P. (2020). Incorporating Prognostic Biomarkers into Risk Assessment Models and TNM Staging for Prostate Cancer. Cells, 9.","DOI":"10.3390\/cells9092116"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.eururo.2015.03.044","article-title":"Adverse Pathologic Features at Radical Prostatectomy: Effect of Preoperative Risk on Oncologic Outcomes","volume":"69","author":"Imnadze","year":"2015","journal-title":"Eur. Urol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.eururo.2013.02.024","article-title":"Timing of Curative Treatment for Prostate Cancer: A Systematic Review","volume":"64","author":"Bergh","year":"2013","journal-title":"Eur. Urol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1097\/JU.0000000000001601","article-title":"Systematic Review of Time to Definitive Treatment for Intermediate Risk and High Risk Prostate Cancer: Are Delays Associated with Worse Outcomes?","volume":"205","author":"Nguyen","year":"2021","journal-title":"J. Urol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1097\/JU.0000000000002420","article-title":"The Natural History of Untreated Biopsy Grade Group Progression and Delayed Definitive Treatment for Men on Active Surveillance for Early-Stage Prostate Cancer","volume":"207","author":"Chappidi","year":"2022","journal-title":"J. Urol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/15\/3558\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:54:33Z","timestamp":1760140473000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/15\/3558"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,22]]},"references-count":31,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["cancers14153558"],"URL":"https:\/\/doi.org\/10.3390\/cancers14153558","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2022,7,22]]}}}