{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:47:58Z","timestamp":1791996478847,"version":"4.4.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"\n Background<\/jats:title>\n Prostate cancer (PC) is the most common cancer in men in the United States with a 5-year relative survival rate for people with distant metastases of 36%. We conducted a single institution, retrospective cohort study of patients with metastatic PC to investigate whether certain gene mutations can be used as predictive biomarkers.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n 200 patients with metastatic hormone sensitive (mHSPC) and castration resistant (mCRPC) prostate cancer who had a FoundationOne report and were treated from June 2007 to October 2024 were included in the study. Disease progression was evaluated according to RECIST criteria, PCWG3 criteria, and PSA values. Assessed gene mutations included\n SPOP, p53, Rb, PTEN<\/jats:italic>\n , and\n HRR<\/jats:italic>\n genes. Overall survival (OS) and progression-free survival (PFS) were calculated for mHSPC and mCRPC.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among 200 patients, there were 182 patients with mHSPC and 174 patients with mCRPC. Average age at diagnosis of metastatic disease was 71.5, ECOG was 0.76, and median PSA was 75.6 ng\/mL. 152 patients had high-volume disease. 102 patients passed away. Patients with a\n p53<\/jats:italic>\n mutation (n=99) had lower OS in mHSPC (50.7 months vs 86.2 months, p&lt;0.01). Patients with a\n PTEN<\/jats:italic>\n mutation (n=50) had a lower OS in mHSPC (50.6 months vs 65.8 months, p=0.03) and mCRPC (29.5 months vs 46.0 months, p=0.04). Patients with\n HRR<\/jats:italic>\n mutations (n=43) had lower OS in mHSPC (41.4 months vs 64.6 months, p&lt;0.01) and mCRPC (18.4 months vs 42.8 months, p=0.04).\n p53<\/jats:italic>\n and\n PTEN<\/jats:italic>\n mutations were associated with shorter PFS in mCRPC (13.8 months vs 23.2 months, p=0.03; 12.2 months vs 22.6 months, p&lt;0.01, respectively). Mutations in\n SPOP<\/jats:italic>\n (n=13 mHSPC, n=9 mCRPC) and\n RB1<\/jats:italic>\n (n=12 mHSPC, n=10 mCRPC) were not associated with statistically significant differences in OS and PFS.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n PTEN<\/jats:italic>\n , and\n HRR<\/jats:italic>\n mutations were associated with shorter OS in both mHSPC and mCRPC.\n p53<\/jats:italic>\n mutations are associated with shorter OS only in mHSPC.\n p53<\/jats:italic>\n and\n PTEN<\/jats:italic>\n mutations were associated with shorter PFS only in mCRPC.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fonc.2026.1772860","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:22:53Z","timestamp":1773033773000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Real-world precision medicine data in metastatic prostate cancer \u2014 a retrospective cohort study"],"prefix":"10.3389","volume":"16","author":[{"given":"Awais","family":"Paracha","sequence":"first","affiliation":[{"name":"Department of Medicine, Northwell Health","place":["New Hyde Park, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Tran","sequence":"additional","affiliation":[{"name":"Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell","place":["Hempstead, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margot","family":"Noyelle","sequence":"additional","affiliation":[{"name":"Department of Medicine, Thomas Jefferson University","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Kapilian","sequence":"additional","affiliation":[{"name":"Department of Medicine, California Pacific Medical Center","place":["San Francisco, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zohair","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Department of Medicine, The University of Tennessee Health Science Center","place":["Memphis, TN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Choppa","sequence":"additional","affiliation":[{"name":"Department of Medicine, Northwell Health","place":["New Hyde Park, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Corsi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Northwell Health","place":["New Hyde Park, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Stone","sequence":"additional","affiliation":[{"name":"Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell","place":["Hempstead, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Hua","family":"Zhu","sequence":"additional","affiliation":[{"name":"Northwell Health Cancer Institute, Northwell Health","place":["New Hyde Park, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.32802","article-title":"Annual report to the nation on the status of cancer, part I: National cancer statistics","volume":"126","author":"Henley","year":"2020","journal-title":"Cancer"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2025.0228","article-title":"Prostate cancer: A review","volume":"333","author":"Raychaudhuri","year":"2025","journal-title":"JAMA"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2023.0050","article-title":"Prostate cancer, version 4.2023, NCCN clinical practice guidelines in oncology","volume":"21","author":"Schaeffer","year":"2023","journal-title":"J Natl Compr Canc Netw"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2024.0591","article-title":"Metastatic hormone-sensitive prostate cancer and combination treatment outcomes: A review","volume":"10","author":"Hussain","year":"2024","journal-title":"JAMA Oncol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e0237802","DOI":"10.1371\/journal.pone.0237802","article-title":"Clinical and analytical validation of FoundationOne Liquid CDx, a novel 324-Gene cfDNA-based comprehensive genomic profiling assay for cancers of solid tumor origin","volume":"15","author":"Woodhouse","year":"2020","journal-title":"PloS One"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.64.2702","article-title":"Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the prostate cancer clinical trials working group 3","volume":"34","author":"Scher","year":"2016","journal-title":"J Clin Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur J Cancer"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26115309","article-title":"Integrating aggressive-variant prostate cancer-associated tumor suppressor gene status with clinical variables to refine prognosis and predict androgen receptor pathway inhibitor response in metastatic hormone-sensitive setting","volume":"26","author":"Pedrani","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.957404","article-title":"Comprehensive analysis of TP53 and SPOP mutations and their impact on survival in metastatic prostate cancer","volume":"12","author":"Zhou","year":"2022","journal-title":"Front Oncol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3923","article-title":"MDM2 and P53 polymorphisms contribute together to the risk and survival of prostate cancer","volume":"7","author":"Xue","year":"2016","journal-title":"Oncotarget"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1172\/JCI132031","article-title":"Genomics of lethal prostate cancer at diagnosis and castration resistance","volume":"130","author":"Mateo","year":"2020","journal-title":"J Clin Invest"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-1943","article-title":"TP53 outperforms other androgen receptor biomarkers to predict abiraterone or enzalutamide outcome in metastatic castration-resistant prostate cancer","volume":"25","author":"De Laere","year":"2019","journal-title":"Clin Cancer Res"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-024-01215-2","article-title":"Metastatic castration-resistant prostate cancer: advances in treatment and symptom management","volume":"25","author":"Kulasegaran","year":"2024","journal-title":"Curr Treat Options Oncol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e2300562","DOI":"10.1200\/PO.23.00562","article-title":"Real-world overall survival and treatment patterns by PTEN status in metastatic castration-resistant prostate cancer","volume":"8","author":"Gupta","year":"2024","journal-title":"JCO Precis Oncol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24372","article-title":"PTEN-PI3K pathway alterations in advanced prostate cancer and clinical implications","author":"Choudhury","year":"2022","journal-title":"Prostate"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol32060331","article-title":"PTEN mutations associated with increased recurrence and decreased survival in patients with prostate cancer spinal metastasis","volume":"32","author":"Antar","year":"2025","journal-title":"Curr Oncol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1381134","article-title":"Prognostic utility of biopsy-based PTEN and ERG status on biochemical progression and overall survival after SBRT for localized prostate cancer","volume":"14","author":"Repka","year":"2024","journal-title":"Front Oncol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/j.eururo.2014.10.027","article-title":"PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate","volume":"67","author":"Ferraldeschi","year":"2015","journal-title":"Eur Urol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.euf.2015.07.005","article-title":"PTEN loss as determined by clinical-grade immunohistochemistry assay is associated with worse recurrence-free survival in prostate cancer","volume":"2","author":"Lotan","year":"2016","journal-title":"Eur Urol Focus"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2025.10.004","article-title":"Capivasertib plus abiraterone in PTEN-deficient metastatic hormone-sensitive prostate cancer: CAPItello-281 phase III study","volume":"37","author":"Fizazi","year":"2025","journal-title":"Ann Oncol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"105569","DOI":"10.1016\/j.esmoop.2025.105569","article-title":"A phase I study of AZD8186 in combination with docetaxel in patients with PTEN-mutated or PIK3CB-mutated advanced solid tumors","volume":"10","author":"Schram","year":"2025","journal-title":"ESMO Open"},{"key":"B22","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1038\/s41698-024-00672-0","article-title":"The intersection of homologous recombination (HR) and mismatch repair (MMR) pathways in DNA repair-defective tumors","volume":"8","author":"Incorvaia","year":"2024","journal-title":"NPJ Precis Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/bju.16462","article-title":"Impact of homologous recombination repair\/BReast CAncer (BRCA) gene alterations on survival in a real-world setting of metastatic prostate cancer","volume":"135","author":"Wenzel","year":"2025","journal-title":"BJU Int"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-025-01323-7","article-title":"Advances in targeted therapy for metastatic prostate cancer","volume":"26","author":"Grewal","year":"2025","journal-title":"Curr Treat Options Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-24-1402","article-title":"Abiraterone, olaparib, or abiraterone + Olaparib in first-line metastatic castration-resistant prostate cancer with DNA repair defects (BRCAAway)","volume":"30","author":"Hussain","year":"2024","journal-title":"Clin Cancer Res"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.02105","article-title":"Efficacy of poly(ADP-ribose) polymerase inhibitors by individual genes in homologous recombination repair gene-mutated metastatic castration-resistant prostate cancer: A US food and drug administration pooled analysis","volume":"42","author":"Fallah","year":"2024","journal-title":"J Clin Oncol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2023.07.013","article-title":"Combining PARP inhibitors and androgen receptor signalling inhibitors in metastatic prostate cancer: A quantitative synthesis and meta-analysis","volume":"7","author":"Messina","year":"2024","journal-title":"Eur Urol Oncol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1159557","article-title":"PARP inhibitors in metastatic prostate cancer","volume":"13","author":"Taylor","year":"2023","journal-title":"Front Oncol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911440","article-title":"Olaparib for metastatic castration-resistant prostate cancer","volume":"382","author":"de Bono","year":"2020","journal-title":"N Engl J Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-22-2801","article-title":"Deregulation of SPOP in cancer","volume":"83","author":"Zhang","year":"2023","journal-title":"Cancer Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26010318","article-title":"The emerging predictive and prognostic role of aggressive-variant-associated tumor suppressor genes across prostate cancer stages","volume":"26","author":"Pedrani","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqaf020","article-title":"Interaction between estrogen receptors and p53: A broader role for tamoxifen","volume":"166","author":"Das","year":"2025","journal-title":"Endocrinology"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/s41391-017-0027-4","article-title":"p53 status in the primary tumor predicts efficacy of subsequent abiraterone and enzalutamide in castration-resistant prostate cancer","volume":"21","author":"Maughan","year":"2018","journal-title":"Prostate Cancer Prostatic Dis"},{"key":"B34","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.eururo.2018.11.045","article-title":"Compound genomic alterations of TP53, PTEN, and RB1 tumor suppressors in localized and metastatic prostate cancer","volume":"76","author":"Hamid","year":"2019","journal-title":"Eur Urol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/s41391-021-00430-4","article-title":"Differential impact of tumor suppressor gene (TP53, PTEN, RB1) alterations and treatment outcomes in metastatic, hormone-sensitive prostate cancer","volume":"25","author":"Velez","year":"2022","journal-title":"Prostate Cancer Prostatic Dis"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17040645","article-title":"TP53 deficiency in the natural history of prostate cancer","volume":"17","author":"Ofner","year":"2025","journal-title":"Cancers (Basel)"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1902651116","article-title":"Genomic correlates of clinical outcome in advanced prostate cancer","volume":"116","author":"Abida","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22073753","article-title":"Hereditary prostate cancer: genes related, target therapy and prevention","volume":"22","author":"Vietri","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.01.011","article-title":"Treatment patterns and outcomes in metastatic castration-resistant prostate cancer patients with and without somatic or germline alterations in homologous recombination repair genes","volume":"35","author":"Olmos","year":"2024","journal-title":"Ann Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1772860\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:22:54Z","timestamp":1773033774000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1772860\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,9]]},"references-count":39,"alternative-id":["10.3389\/fonc.2026.1772860"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1772860","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,9]]},"article-number":"1772860"}}