{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T23:21:00Z","timestamp":1782256860048,"version":"3.54.5"},"reference-count":30,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"\n PURPOSE<\/jats:title>\n \n Previous studies suggest that\n SPOP<\/jats:italic>\n mutations result in increased sensitivity to androgen receptor pathway inhibitors (ARPIs) but are limited by lack of granular data. We hypothesize that\n SPOP<\/jats:italic>\n mutations are associated with improved outcomes across the spectrum of advanced prostate cancer (PC).\n <\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n Using the real-world clinicogenomic Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort database, we analyzed outcomes based on\n SPOP<\/jats:italic>\n mutation status. The primary end point was overall survival (OS) from the diagnosis of metastatic disease. Secondary end points included real-world progression-free survival (PFS) and PSA90 response.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Among 2,097 patients with metastatic PC, 5.5% (N = 115) had\n SPOP<\/jats:italic>\n -mutated tumors. Compared with\n SPOP<\/jats:italic>\n wild-type, patients with\n SPOP<\/jats:italic>\n mutations were older at diagnosis (median 65\n v<\/jats:italic>\n 63 years;\n P<\/jats:italic>\n = .001) and had higher (\u22658) Gleason sum (68%\n v<\/jats:italic>\n 54%;\n P<\/jats:italic>\n = .02), higher incidence of lung metastasis (17%\n v<\/jats:italic>\n 6%;\n P<\/jats:italic>\n = .001), and increased frequency of intraductal features (13%\n v<\/jats:italic>\n 5%;\n P<\/jats:italic>\n < .001).\n SPOP<\/jats:italic>\n mutations were associated with improved PSA90 response with first ARPI exposure in the castrate-resistant setting (60%\n v<\/jats:italic>\n 40.6%; OR, 2.20 [95% CI, 1.15 to 4.19];\n P<\/jats:italic>\n = .02) but not in the castrate-sensitive setting (78.9%\n v<\/jats:italic>\n 71.5%; OR, 1.49 [95% CI, 0.66 to 3.37];\n P<\/jats:italic>\n = .43). Median PFS with first ARPI did not differ in\n SPOP-<\/jats:italic>\n mutated versus wild-type group in both the castrate-sensitive (24.2\n v<\/jats:italic>\n 19.2 months; hazard ratio [HR], 0.80 [95% CI, 0.49 to 1.32];\n P<\/jats:italic>\n = .39) and castrate-resistant settings (15.0\n v<\/jats:italic>\n 12.4 months; HR, 0.81 [95% CI, 0.58 to 1.12];\n P<\/jats:italic>\n = .20). In multivariable analysis,\n SPOP<\/jats:italic>\n mutations were associated with improved OS (HR, 0.65,\n P<\/jats:italic>\n = .02).\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSION<\/jats:title>\n \n SPOP<\/jats:italic>\n mutations were associated with longer OS despite the presence of aggressive clinical features. The distinct clinical and molecular features of\n SPOP<\/jats:italic>\n -mutated PC support its consideration as a unique molecular subtype with prognostic implications.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1200\/po-25-00590","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T20:58:07Z","timestamp":1764968287000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Impact of\n SPOP<\/i>\n Mutations on Clinical Outcomes in Metastatic Prostate Cancer"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6999-1901","authenticated-orcid":true,"given":"Deepak","family":"Kilari","sequence":"first","affiliation":[{"name":"Department of Medicine, Medical College of Wisconsin, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3184-0945","authenticated-orcid":true,"given":"Nicholas C.","family":"Henderson","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyra","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Yao","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0998-323X","authenticated-orcid":true,"given":"Clara","family":"Hwang","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, Henry Ford Cancer Institute, Detroit, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8890-2951","authenticated-orcid":true,"given":"Pedro C.","family":"Barata","sequence":"additional","affiliation":[{"name":"University Hospitals Seidman Cancer Center, Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4003-1103","authenticated-orcid":true,"given":"Mehmet Asim","family":"Bilen","sequence":"additional","affiliation":[{"name":"Winship Cancer Institute of Emory University, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4371-572X","authenticated-orcid":true,"given":"Laura","family":"Graham","sequence":"additional","affiliation":[{"name":"University of Colorado, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7244-5602","authenticated-orcid":true,"given":"Rohan","family":"Garje","sequence":"additional","affiliation":[{"name":"Miami Cancer Institute, Baptist Health South Florida, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoshana","family":"Rothstein","sequence":"additional","affiliation":[{"name":"Karmanos Cancer Institute, Wayne State University, Detroit, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8132-8646","authenticated-orcid":true,"given":"Shabi","family":"Haider","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical College of Wisconsin, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1311-5416","authenticated-orcid":true,"given":"Joseph J.","family":"Park","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Center for Prostate and Urologic Cancer, Division of Medical Oncology, Duke University Medical Center, Duke University, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6587-4954","authenticated-orcid":true,"given":"Ruben","family":"Raychaudhuri","sequence":"additional","affiliation":[{"name":"University of Washington\/Fred Hutchinson Cancer Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1034-2971","authenticated-orcid":true,"given":"Amanda","family":"Pilling","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, Henry Ford Cancer Institute, Detroit, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Chin","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2277-8668","authenticated-orcid":true,"given":"Vadim S.","family":"Koshkin","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5198-0673","authenticated-orcid":true,"given":"Abhishek","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0075-3745","authenticated-orcid":true,"given":"Frank Cameron","family":"Cackowski","sequence":"additional","affiliation":[{"name":"Karmanos Cancer Institute, Wayne State University, Detroit, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2302-4171","authenticated-orcid":true,"given":"Jones T.","family":"Nauseef","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0821-6503","authenticated-orcid":true,"given":"Alexandra","family":"Sokolova","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Medical Oncology, Oregon Health and Science University, Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8070-7927","authenticated-orcid":true,"given":"Adanma","family":"Ayanambakkam","sequence":"additional","affiliation":[{"name":"Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9480-2626","authenticated-orcid":true,"given":"Yousef","family":"Zakharia","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Medical Oncology, Mayo Clinic, Phoenix, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Thomas","family":"Schweizer","sequence":"additional","affiliation":[{"name":"University of Washington\/Fred Hutchinson Cancer Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7012-1754","authenticated-orcid":true,"given":"Andrew J.","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Center for Prostate and Urologic Cancer, Division of Medical Oncology, Duke University Medical Center, Duke University, Durham, 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