{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T13:42:10Z","timestamp":1765806130392,"version":"3.48.0"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T00:00:00Z","timestamp":1759622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Survival differs markedly between men with metastatic prostate cancer (mPC) confined to lymph nodes (LNM) versus bone (BM). We examined whether site\u2010specific genomic alterations\u2014and their combinations\u2014explain this disparity and could inform intensity\u2010modulated follow\u2010up or therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Clinical and targeted\u2010sequencing data for 1011 men with mPC in the cBioPortal for Cancer Genomics registry were analyzed (LNM\u2010only\u2009=\u2009622; BM\u2010only\u2009=\u2009389). Genes altered in &gt;\u20095% of tumors (two\u2010sided\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) were assessed individually and in every possible multigene cluster for associations with overall survival (OS). Survival was evaluated with Kaplan\u2013Meier curves and the difference in restricted mean survival time (dRMST) to pinpoint the first significant curve divergence. Synthetic\u2013lethal (SL) interactions were explored via the SLOAD database.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In total, 18 of 184 profiled genes (9.8%) exceeded the 5% alteration threshold. FOXA1 was enriched in BM, whereas TMPRSS2, ERG, PTEN, ZFHX3, CDK12, and KMT2C were enriched in LNM (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Among 9143 tested gene clusters, 65 were associated with inferior OS; 48 occurred in the LNM subgroup, 17 in the combined cohort, and none in the BM alone. High\u2010risk clusters showed first OS divergence 10\u201360 months after diagnosis of metastasis. SLOAD identified 615 putative SL pairs involving these genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We identified 65 site\u2010specific multigene clusters\u2014chiefly in lymph node\u2010only mPC\u2014that underlie the survival gap between nodal and bone metastases. These signatures suggest a 10\u201360\u2010month interval that may lend itself for intensity\u2010modulated follow\u2010up. We also discovered hundreds of synthetic\u2013lethal gene\u2013alteration pairs, opening future research opportunities in combinatorial therapeutic targeting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.70070","type":"journal-article","created":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T13:10:42Z","timestamp":1759669842000},"page":"196-203","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetics\u2010Driven, Intensity\u2010Modulated Adaptive Management of Patients With Metastatic Prostate Cancer"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7060-0027","authenticated-orcid":false,"given":"Reynier D. Rodriguez","family":"Rosales","sequence":"first","affiliation":[{"name":"Department of Urology University of Florida College of Medicine \u2013 Jacksonville Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arjun","family":"Venkatesh","sequence":"additional","affiliation":[{"name":"Department of Urology University of Florida College of Medicine \u2013 Jacksonville Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean\u2010Pierre","family":"Kanumuambidi","sequence":"additional","affiliation":[{"name":"Department of Urology University of Florida College of Medicine \u2013 Jacksonville Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yudai","family":"Ishiyama","sequence":"additional","affiliation":[{"name":"Department of Urology University of Florida College of Medicine \u2013 Jacksonville Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Al\u2010Toubat","sequence":"additional","affiliation":[{"name":"Department of Urology University of Florida College of Medicine \u2013 Jacksonville Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hunter","family":"Sceats","sequence":"additional","affiliation":[{"name":"Department of Urology University of Florida College of Medicine \u2013 Jacksonville Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas D.","family":"Metzner","sequence":"additional","affiliation":[{"name":"Department of Urology University of Florida College of Medicine \u2013 Jacksonville Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelby","family":"Sparks","sequence":"additional","affiliation":[{"name":"Department of Urology University of Florida College of Medicine \u2013 Jacksonville Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8381-092X","authenticated-orcid":false,"given":"Nicole","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Urology University of Florida College of Medicine \u2013 Jacksonville Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Bandyk","sequence":"additional","affiliation":[{"name":"Department of Urology University of Florida College of Medicine \u2013 Jacksonville Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. C.","family":"Balaji","sequence":"additional","affiliation":[{"name":"Department of Urology University of Florida College of Medicine \u2013 Jacksonville Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,5]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000003452"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2019.5011"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.67.8045"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.64.2488"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-13-152"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.2797"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17781"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2022.01.015"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15098"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2023.41.16_suppl.e17119"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2023.10.012"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0095"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.4103\/sja.SJA_543_18"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2025.02.006"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-19425-7"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2107322"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.75.3657"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/database\/baac075"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2011.06.018"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1347-4"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2023.02.006"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.JU.0001008572.33286.63"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-023-02920-2"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2022.01.015"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-3564450\/v1"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-23-3785"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2019.09.036"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1200\/po.19.00399"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2025.152221"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djae224"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-24-3471"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.70070","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T13:32:34Z","timestamp":1765805554000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.70070"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,5]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/pros.70070"],"URL":"https:\/\/doi.org\/10.1002\/pros.70070","archive":["Portico"],"relation":{},"ISSN":["0270-4137","1097-0045"],"issn-type":[{"type":"print","value":"0270-4137"},{"type":"electronic","value":"1097-0045"}],"subject":[],"published":{"date-parts":[[2025,10,5]]},"assertion":[{"value":"2025-06-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}