{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T22:37:45Z","timestamp":1786747065236,"version":"build-2736575974"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We sought to assess how centrally reviewed radical prostatectomy (RP) Grade Group (GG), tumor volume (TV), prostate-specific antigen density (PSAD), pathologic stage, tumor topography, patient age, and race and ethnicity relate to regional lymph node metastasis (LN+).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We reviewed patient cases with treatment-naive RPs performed from 2013 through 2026. All specimens underwent centralized histologic review by 1 urologic pathologist. Grade Group was assigned from the highest-grade tumor, and its TV was measured. Tumor volume and PSAD were modeled on the log2 scale (odds ratios per doubling), and multivariable Firth penalized logistic regression assessed factors associated with LN+.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>No metastasis was seen in GG1 cases (n\u2009=\u2009368). The final cohort comprised 3142 node-staged GG2 to GG5 RP specimens. Positive regional LNs were identified in 135 (4.3%) patients, with a median of 1 positive node (IRQ, 1-2 LNs; range, 1-17 LNs). Cases with LN+\u2009disease had a median of 9 LNs (range, 1-31 LNs) examined compared with 5 LNs (range, 1-45 LNs) in cases without metastasis (P\u2009&amp;lt;\u2009.001). Grade Group 5 cancer was associated with a clinically significantly lower value for PSAD divided by TV (PSAD\/TV) than for GG2 to GG4 cancers. In the augmented multivariable Firth model, PSAD, TV, GG, posterior or extensive bilateral topography, and pT3a\/pT3b stage were independently associated with LN+. Age, race, and ethnicity were not independently associated. Anterior topography inversely correlated with LN+.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this centrally reviewed RP cohort, no LN+\u2009was observed in GG1 cancer. Among GG2 to GG5 cancers, LN+\u2009was associated with increasing GG, larger TV, higher PSAD, pT3a\/pT3b stage, and posterior or extensive bilateral topography after adjustment for age, race, and ethnicity. Grade Group 5 cancers showed lower PSA production than did GG2 to GG4 cancers, indicating a different PSAD-TV relationship.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ajcp\/aqag095","type":"journal-article","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T11:36:17Z","timestamp":1784979377000},"source":"Crossref","is-referenced-by-count":0,"title":["Risk factors for lymph node metastasis in a contemporary radical prostatectomy cohort"],"prefix":"10.1093","volume":"166","author":[{"given":"Oleksii A","family":"Iakymenko","sequence":"first","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of Miami Miller School of Medicine , Miami, FL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheida","family":"Khosravaniardakani","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of Miami Miller School of Medicine , Miami, FL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica","family":"Menendez","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of Miami Miller School of Medicine , Miami, FL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasha R","family":"Sioni","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of Miami Miller School of Medicine , Miami, FL,","place":["United States"]},{"name":"Health Management and Policy Department, University of Miami Herbert Business School , Miami, FL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merce","family":"Jorda","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of Miami Miller School of Medicine , Miami, FL,","place":["United States"]},{"name":"Desai Sethi Urology Institute, University of Miami Miller School of Medicine , Miami, FL,","place":["United States"]},{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine , Miami, FL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0383-7311","authenticated-orcid":false,"given":"Sanoj","family":"Punnen","sequence":"additional","affiliation":[{"name":"Desai Sethi Urology Institute, University of Miami Miller School of Medicine , Miami, FL,","place":["United States"]},{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine , Miami, FL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipen J","family":"Parekh","sequence":"additional","affiliation":[{"name":"Desai Sethi Urology Institute, University of Miami Miller School of Medicine , Miami, FL,","place":["United States"]},{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine , Miami, FL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark L","family":"Gonzalgo","sequence":"additional","affiliation":[{"name":"Desai Sethi Urology Institute, University of Miami Miller School of Medicine , Miami, FL,","place":["United States"]},{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine , Miami, FL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleksandr N","family":"Kryvenko","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of Miami Miller School of Medicine , Miami, FL,","place":["United States"]},{"name":"Health Management and Policy Department, University of Miami Herbert Business School , Miami, FL,","place":["United States"]},{"name":"Desai Sethi Urology Institute, University of Miami Miller School of Medicine , Miami, FL,","place":["United States"]},{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine , Miami, FL,","place":["United States"]},{"name":"Department of Radiation Oncology, University of Miami Miller School of Medicine , Miami, FL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"2026081418190656200_aqag095-B1","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1002\/1097-0142(20010101)91:1\u2009&lt;\u200966::AID-CNCR9\u2009&gt;\u20093.0.CO;2-P","article-title":"Risk of prostate carcinoma death in patients with lymph node metastasis","volume":"91","author":"Cheng","year":"2001","journal-title":"Cancer"},{"key":"2026081418190656200_aqag095-B2","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/s0022-5347(17)38748-7","article-title":"Prognostic significance of lymph nodal metastases in prostate cancer","volume":"142","author":"Gervasi","year":"1989","journal-title":"J Urol"},{"key":"2026081418190656200_aqag095-B3","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1097\/JU.0000000000003452","article-title":"Updates to advanced prostate cancer: AUA\/SUO guideline (2023)","volume":"209","author":"Lowrance","year":"2023","journal-title":"J Urol"},{"key":"2026081418190656200_aqag095-B4","doi-asserted-by":"publisher","first-page":"469","DOI":"10.6004\/jnccn.2025.0052","article-title":"Prostate Cancer, Version 3.2026, NCCN Clinical Practice Guidelines in Oncology","volume":"23","author":"Spratt","year":"2025","journal-title":"J Natl Compr Canc Netw"},{"key":"2026081418190656200_aqag095-B5","doi-asserted-by":"publisher","first-page":"610","DOI":"10.5858\/arpa.2012-0128-OA","article-title":"Gleason score 7 adenocarcinoma of the prostate with lymph node metastases: analysis of 184 radical prostatectomy specimens","volume":"137","author":"Kryvenko","year":"2013","journal-title":"Arch Pathol Lab Med"},{"key":"2026081418190656200_aqag095-B6","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1177\/1066896912445921","article-title":"Characteristics of pelvic lymph node metastases in prostatic adenocarcinoma: a study of 83 cases","volume":"20","author":"Yoon","year":"2012","journal-title":"Int J Surg Pathol"},{"key":"2026081418190656200_aqag095-B7","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1097\/PAS.0b013e3182556dcd","article-title":"Do\u00a0adenocarcinomas of the prostate with Gleason score (GS)\u2009\u2264\u20096 have the potential to metastasize to lymph nodes?","volume":"36","author":"Ross","year":"2012","journal-title":"Am J Surg Pathol"},{"key":"2026081418190656200_aqag095-B8","doi-asserted-by":"publisher","first-page":"31.e1","DOI":"10.1016\/j.urolonc.2016.08.004","article-title":"Risk of lymph node metastases in pathological Gleason score \u22646 prostate adenocarcinoma: analysis of institutional and population-based databases","volume":"35","author":"Wenger","year":"2017","journal-title":"Urol Oncol"},{"key":"2026081418190656200_aqag095-B9","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1097\/PAT.0000000000000097","article-title":"Nationwide prevalence of lymph node metastases in Gleason score 3\u2009+\u20093 = 6 prostate cancer","volume":"46","author":"Liu","year":"2014","journal-title":"Pathology"},{"key":"2026081418190656200_aqag095-B10","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1177\/1066896915600519","article-title":"Average weight of seminal vesicles: an adjustment factor for radical prostatectomy specimens weighed with seminal vesicles","volume":"23","author":"Tjionas","year":"2015","journal-title":"Int J Surg Pathol"},{"key":"2026081418190656200_aqag095-B11","doi-asserted-by":"publisher","first-page":"461","DOI":"10.5858\/arpa.2020-0015-RA","article-title":"The 2019 Genitourinary Pathology Society (GUPS) white paper on contemporary grading of prostate cancer","volume":"145","author":"Epstein","year":"2021","journal-title":"Arch Pathol Lab Med"},{"key":"2026081418190656200_aqag095-B12","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.5858\/arpa.2015-0487-SA","article-title":"Prostate cancer grading: a decade after the 2005 modified Gleason grading system","volume":"140","author":"Kryvenko","year":"2016","journal-title":"Arch Pathol Lab Med"},{"key":"2026081418190656200_aqag095-B13","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.5858\/arpa.2021-0279-OA","article-title":"Variance of tumor grade at radical prostatectomy with assessment of each tumor nodule versus global grading","volume":"146","author":"Iakymenko","year":"2022","journal-title":"Arch Pathol Lab Med"},{"key":"2026081418190656200_aqag095-B14","author":"College of American Pathologists"},{"key":"2026081418190656200_aqag095-B15","doi-asserted-by":"publisher","first-page":"833","DOI":"10.5858\/arpa.2021-0104-OA","article-title":"Anterior or posterior prostate cancer tumor nodule location predicts likelihood of certain adverse outcomes at radical prostatectomy","volume":"146","author":"Hayee","year":"2022","journal-title":"Arch Pathol Lab Med"},{"key":"2026081418190656200_aqag095-B16","doi-asserted-by":"publisher","first-page":"1862","DOI":"10.1097\/PAS.0b013e3181fc679e","article-title":"Prostate cancer topography and patterns of lymph node metastasis","volume":"34","author":"Tokuda","year":"2010","journal-title":"Am J Surg Pathol"},{"key":"2026081418190656200_aqag095-B17","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1097\/PAS.0000000000001417","article-title":"Reporting practices and resource utilization in the era of intraductal carcinoma of the prostate: a survey of genitourinary subspecialists","volume":"44","author":"Gandhi","year":"2020","journal-title":"Am J Surg Pathol"},{"key":"2026081418190656200_aqag095-B18","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1097\/PAS.0000000000000530","article-title":"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","volume":"40","author":"Epstein","year":"2016","journal-title":"Am J Surg Pathol"},{"key":"2026081418190656200_aqag095-B19","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1002\/pros.23199","article-title":"Re: Clinical significance of prospectively assigned Gleason tertiary pattern 4 in contemporary Gleason score 3\u2009+\u20093 = 6 prostate cancer","volume":"76","author":"Kryvenko","year":"2016","journal-title":"Prostate"},{"key":"2026081418190656200_aqag095-B20","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.eururo.2020.10.033","article-title":"A comparison of Genitourinary Society Pathology and International Society of Urological Pathology prostate cancer guidelines","volume":"79","author":"Epstein","year":"2021","journal-title":"Eur Urol"},{"key":"2026081418190656200_aqag095-B21","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.urology.2019.10.014","article-title":"Prostatic ductal adenocarcinoma controlled for cancer grade and tumor volume does not have an independent effect on adverse radical prostatectomy outcomes compared to usual acinar prostatic adenocarcinoma","volume":"137","author":"Iakymenko","year":"2020","journal-title":"Urology"},{"key":"2026081418190656200_aqag095-B22","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.5858\/arpa.2021-0048-OA","article-title":"Prostatic ductal adenocarcinoma controlled for tumor grade, stage, and margin status does not independently influence the likelihood of biochemical recurrence in localized prostate cancer after radical prostatectomy","volume":"146","author":"Kryvenko","year":"2022","journal-title":"Arch Pathol Lab Med"},{"key":"2026081418190656200_aqag095-B23","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1016\/j.urology.2013.12.054","article-title":"Biopsy criteria for determining appropriateness for active surveillance in the modern era","volume":"83","author":"Kryvenko","year":"2014","journal-title":"Urology"},{"key":"2026081418190656200_aqag095-B24","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1097\/PAT.0000000000000263","article-title":"Re: Nationwide prevalence of lymph node metastases in Gleason score 3\u2009+\u20093 = 6 prostate cancer","volume":"47","author":"Kryvenko","year":"2015","journal-title":"Pathology"},{"key":"2026081418190656200_aqag095-B25","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1111\/bju.12879","article-title":"Disease-specific death and metastasis do not occur in patients with Gleason score \u22646 at radical prostatectomy","volume":"116","author":"Kweldam","year":"2015","journal-title":"BJU Int"},{"key":"2026081418190656200_aqag095-B26","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1007\/s00345-023-04724-1","article-title":"Size of lymph-node metastases in prostate cancer patients undergoing radical prostatectomy: implication for imaging and oncologic follow-up of 2705 lymph-node positive patients","volume":"42","author":"Falkenbach","year":"2024","journal-title":"World J Urol"},{"key":"2026081418190656200_aqag095-B27","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1001\/jamaoncol.2021.3771","article-title":"Diagnostic accuracy of 68Ga-PSMA-11 PET for pelvic nodal metastasis detection prior to radical prostatectomy and pelvic lymph node dissection: a multicenter prospective phase 3 imaging trial","volume":"7","author":"Hope","year":"2021","journal-title":"JAMA Oncol"},{"key":"2026081418190656200_aqag095-B28","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.euo.2025.01.004","article-title":"External validation of nomograms for the identification of pelvic nodal dissection candidates among prostate cancer patients with negative preoperative prostate-specific membrane antigen positron emission tomography","volume":"9","author":"Gandaglia","year":"2026","journal-title":"Eur\u00a0Urol Oncol"},{"key":"2026081418190656200_aqag095-B29","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1001\/jama.1994.03510290050036","article-title":"Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer","volume":"271","author":"Epstein","year":"1994","journal-title":"JAMA"},{"key":"2026081418190656200_aqag095-B30","doi-asserted-by":"publisher","first-page":"1664","DOI":"10.1016\/j.juro.2016.06.013","article-title":"Definition of insignificant tumor volume of Gleason score 3\u2009+\u20093 = 6 (Grade Group 1) prostate cancer at radical prostatectomy-is it time to increase the threshold?","volume":"196","author":"Kryvenko","year":"2016","journal-title":"J Urol"},{"key":"2026081418190656200_aqag095-B31","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1002\/pros.24183","article-title":"Percentage of Gleason pattern 4 and tumor volume predict adverse pathological stage and margin status at radical prostatectomy in Grade Group 2 and Grade Group 3 prostate cancers","volume":"81","author":"Iakymenko","year":"2021","journal-title":"Prostate"},{"key":"2026081418190656200_aqag095-B32","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/j.path.2018.07.003","article-title":"Updates on grading and staging of prostate cancer","volume":"11","author":"Braunhut","year":"2018","journal-title":"Surg Pathol Clin"},{"key":"2026081418190656200_aqag095-B33","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1016\/S0022-5347(05)67532-5","article-title":"Correlation of serum prostate specific antigen and quantitative immunohistochemistry","volume":"163","author":"Weir","year":"2000","journal-title":"J Urol"},{"key":"2026081418190656200_aqag095-B34","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.eururo.2020.11.015","article-title":"Ductal prostate cancers demonstrate poor outcomes with conventional therapies","volume":"79","author":"Ranasinghe","year":"2021","journal-title":"Eur Urol"},{"key":"2026081418190656200_aqag095-B35","doi-asserted-by":"publisher","first-page":"2017","DOI":"10.1007\/s00345-022-04065-5","article-title":"Prostate cancer upgrading and adverse pathology in Hispanic men undergoing radical prostatectomy","volume":"40","author":"Hougen","year":"2022","journal-title":"World J Urol"},{"key":"2026081418190656200_aqag095-B36","doi-asserted-by":"publisher","first-page":"288.e1","DOI":"10.1016\/j.urolonc.2024.05.003","article-title":"Prostate cancer patients with lymphatic node involvement detected by immunohistochemistry. Is the effort worthwhile?","volume":"42","author":"de Pablos-Rodr\u00edguez","year":"2024","journal-title":"Urol Oncol"},{"key":"2026081418190656200_aqag095-B37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.euros.2022.07.005","article-title":"Prediction of biochemical recurrence based on molecular detection of lymph node metastasis after radical prostatectomy","volume":"44","author":"\u00d6zdemir","year":"2022","journal-title":"Eur Urol Open Sci"},{"key":"2026081418190656200_aqag095-B38","doi-asserted-by":"publisher","first-page":"2735","DOI":"10.1200\/JCO.2005.05.4767","article-title":"Detection of occult lymph node metastases in locally advanced node-negative prostate cancer","volume":"24","author":"Pagliarulo","year":"2006","journal-title":"J Clin Oncol"},{"key":"2026081418190656200_aqag095-B39","doi-asserted-by":"publisher","first-page":"2577","DOI":"10.1002\/1097-0142(20001215)89:12\u2009&lt;\u20092577::AID-CNCR10\u2009&gt;\u20093.3.CO;2-M","article-title":"Molecular and immunohistochemical staging of men with seminal vesicle invasion and negative pelvic lymph nodes at radical prostatectomy","volume":"89","author":"Potter","year":"2000","journal-title":"Cancer"},{"key":"2026081418190656200_aqag095-B40","doi-asserted-by":"publisher","first-page":"e55","DOI":"10.1016\/j.clgc.2014.08.004","article-title":"Nodal occult metastases in intermediate- and high-risk prostate cancer patients detected using serial section, immunohistochemistry, and real-time reverse transcriptase polymerase chain reaction: prospective evaluation with matched-pair analysis","volume":"13","author":"Schiavina","year":"2015","journal-title":"Clin Genitourin Cancer"},{"key":"2026081418190656200_aqag095-B41","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/s0302-2838(02)00450-5","article-title":"The influence of serial sections, immunohistochemistry, and extension of pelvic lymph node dissection on the lymph node status in clinically localized prostate cancer","volume":"43","author":"Wawroschek","year":"2003","journal-title":"Eur Urol"}],"container-title":["American Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajcp\/article-pdf\/166\/2\/aqag095\/70653612\/aqag095.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajcp\/article-pdf\/166\/2\/aqag095\/70653612\/aqag095.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T22:19:12Z","timestamp":1786745952000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajcp\/article\/doi\/10.1093\/ajcp\/aqag095\/8761890"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":41,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,8,4]]}},"URL":"https:\/\/doi.org\/10.1093\/ajcp\/aqag095","relation":{},"ISSN":["0002-9173","1943-7722"],"issn-type":[{"value":"0002-9173","type":"print"},{"value":"1943-7722","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,8]]},"published":{"date-parts":[[2026,8]]},"article-number":"aqag095"}}