{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T17:06:55Z","timestamp":1792861615884,"version":"4.5.0"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T00:00:00Z","timestamp":1726185600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T00:00:00Z","timestamp":1726185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004324","name":"Astellas Pharma US","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004324","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Prostate Cancer Prostatic Dis"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The natural history of biochemical recurrence (BCR) managed with delayed hormonal therapy is well documented by data from Johns Hopkins. However, as many patients receive treatment prior to metastasis, we evaluated the natural history and role of prostate-specific antigen doubling time (PSADT) in a more contemporary cohort of BCR patients with nonmetastatic castration-sensitive prostate cancer (nmCSPC).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Patients in the Veterans Health Administration (VHA; 01\/01\/06 to 06\/22\/20) with nmCSPC and BCR were divided into rapid (\u2009\u22649 months) and less rapid (\u2009&gt;9 to \u226415 months) PSADT cohorts. Patients with PSADT\u2009&gt;15 months were excluded as outcomes, even with delayed treatment, are excellent. Outcomes included time to first antineoplastic therapy after BCR, metastasis, metastasis-free survival (MFS), and overall survival (OS). Cox models adjusted for baseline demographics and clinical characteristics.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Overall, 781 patients with BCR were identified (502 rapid; 279 less rapid PSADT). Rapid PSADT was associated with shorter time to first systemic antineoplastic therapy (median 11.4 vs. 28.3 months, adjusted hazard ratio [95% confidence interval] 2.17 [1.83\u20132.57]), metastasis (102.4 months vs. not reached, 1.79 [1.33\u20132.40]), MFS (76.1 vs. 106.3 months, 1.73 [1.33\u20132.24]), and OS (120.5 vs. 140.5 months, 1.76 [1.22\u20132.54]) versus less rapid PSADT.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Most patients with rapid PSADT underwent secondary treatment within 1 year after BCR. More contemporary patients treated with early secondary treatment had better outcomes than historical data from patients who had delayed treatment. Whether these results reflect the benefits of early secondary treatment or overall improvements in prostate cancer outcomes over time requires further study.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1038\/s41391-024-00894-0","type":"journal-article","created":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T07:03:29Z","timestamp":1726211009000},"page":"809-816","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Real-world outcomes following biochemical recurrence after definitive therapy with a short prostate-specific antigen doubling time: potential role of early secondary treatment"],"prefix":"10.1038","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8104-6419","authenticated-orcid":false,"given":"Stephen J.","family":"Freedland","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Lax","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbo","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0890-0268","authenticated-orcid":false,"given":"Krishnan","family":"Ramaswamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Russell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4028-9676","authenticated-orcid":false,"given":"Jasmina I.","family":"Ivanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,13]]},"reference":[{"key":"894_CR1","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1001\/jama.294.4.433","volume":"294","author":"SJ Freedland","year":"2005","unstructured":"Freedland SJ, Humphreys EB, Mangold LA, Eisenberger M, Dorey FJ, Walsh PC, et al. Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA. 2005;294:433\u20139.","journal-title":"JAMA"},{"key":"894_CR2","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1111\/j.1464-410X.2011.10422.x","volume":"109","author":"ES Antonarakis","year":"2012","unstructured":"Antonarakis ES, Feng Z, Trock BJ, Humphreys EB, Carducci MA, Partin AW, et al. The natural history of metastatic progression in men with prostate-specific antigen recurrence after radical prostatectomy: long-term follow-up. BJU Int. 2012;109:32\u20139.","journal-title":"BJU Int"},{"key":"894_CR3","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1001\/jama.281.17.1591","volume":"281","author":"CR Pound","year":"1999","unstructured":"Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999;281:1591\u20137.","journal-title":"JAMA."},{"key":"894_CR4","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1200\/JCO.2006.08.0572","volume":"25","author":"SJ Freedland","year":"2007","unstructured":"Freedland SJ, Humphreys EB, Mangold LA, Eisenberger M, Dorey FJ, Walsh PC, et al. Death in patients with recurrent prostate cancer after radical prostatectomy: prostate-specific antigen doubling time subgroups and their associated contributions to all-cause mortality. J Clin Oncol. 2007;25:1765\u201371.","journal-title":"J Clin Oncol"},{"key":"894_CR5","unstructured":"Mottet N, Cornford P, van den Berg RCN, Briers E, Eberli D, De Meerleer G, et al. EAU - EANM - ESTRO - ESUR - ISUP - SIOG guidelines on prostate cancer. 2023. https:\/\/d56bochluxqnz.cloudfront.net\/documents\/full-guideline\/EAU-EANM-ESTRO-ESUR-ISUP-SIOG-Guidelines-on-Prostate-Cancer-2023_2023-03-27-131655_pdvy.pdf."},{"key":"894_CR6","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1016\/j.annonc.2020.06.011","volume":"31","author":"C Parker","year":"2020","unstructured":"Parker C, Castro E, Fizazi K, Heidenreich A, Ost P, Procopio G, et al. Prostate cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31:1119\u201334.","journal-title":"Ann Oncol"},{"key":"894_CR7","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1097\/JU.0000000000001375","volume":"205","author":"WT Lowrance","year":"2021","unstructured":"Lowrance WT, Breau RH, Chou R, Chapin BF, Crispino T, Dreicer R, et al. Advanced prostate cancer: AUA\/ASTRO\/SUO guideline PART I. J Urol. 2021;205:14\u201321.","journal-title":"J Urol"},{"key":"894_CR8","doi-asserted-by":"crossref","unstructured":"Virgo KS, Rumble RB, Talcott J. Initial management of noncastrate advanced, recurrent, or metastatic prostate cancer: ASCO guideline update. J Clin Oncol. 2023:JCO.23.00155.","DOI":"10.1200\/OP.23.00346"},{"key":"894_CR9","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1097\/UPJ.0000000000000189","volume":"8","author":"A Moradzadeh","year":"2021","unstructured":"Moradzadeh A, Howard LE, Freedland SJ, Amling CL, Aronson WJ, Cooperberg MR, et al. The impact of comorbidity and age on timing of androgen deprivation therapy in men with biochemical recurrence after radical prostatectomy. Urol Pract. 2021;8:238\u201345.","journal-title":"Urol Pract"},{"key":"894_CR10","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/S1470-2045(16)00107-8","volume":"17","author":"GM Duchesne","year":"2016","unstructured":"Duchesne GM, Woo HH, Bassett JK, Bowe SJ, D\u2019Este C, Frydenberg M, et al. Timing of androgen-deprivation therapy in patients with prostate cancer with a rising PSA (TROG 03.06 and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial. Lancet Oncol. 2016;17:727\u201337.","journal-title":"Lancet Oncol"},{"key":"894_CR11","doi-asserted-by":"publisher","first-page":"5018","DOI":"10.1200\/JCO.2018.36.15_suppl.5018","volume":"36","author":"A Loblaw","year":"2018","unstructured":"Loblaw A, Bassett J, D\u2019Este C, Pond GR, Cheung P, Millar JL, et al. Timing of androgen deprivation therapy for prostate cancer patients after radiation: planned combined analysis of two randomized phase 3 trials. J Clin Oncol. 2018;36:5018\u20135018.","journal-title":"J Clin Oncol"},{"key":"894_CR12","unstructured":"US Department of Veterans Affairs. About VHA. 2022. https:\/\/www.va.gov\/health\/aboutvha.asp."},{"key":"894_CR13","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1056\/NEJMoa2303974","volume":"389","author":"SJ Freedland","year":"2023","unstructured":"Freedland SJ, de Almeida Luz M, De Giorgi U, Gleave M, Gotto GT, Pieczonka CM, et al. Improved outcomes with enzalutamide in biochemically recurrent prostate cancer. N Engl J Med. 2023;389:1453\u201365.","journal-title":"N Engl J Med"},{"key":"894_CR14","doi-asserted-by":"publisher","first-page":"S1175","DOI":"10.1016\/j.annonc.2022.07.1516","volume":"33","author":"DJ George","year":"2022","unstructured":"George DJ, Sandin R, Agarwal N, Tagawa ST, Klaassen Z, Bitting R, et al. 1384P Treatment patterns and overall survival (OS) in metastatic castration-sensitive prostate cancer (mCSPC) from 2010 to 2019. Ann Oncol. 2022;33:S1175\u2013S1176.","journal-title":"Ann Oncol"},{"key":"894_CR15","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.euo.2021.04.008","volume":"4","author":"MJ Morris","year":"2021","unstructured":"Morris MJ, Mota JM, Lacuna K, Hilden P, Gleave M, Carducci MA, et al. Phase 3 randomized controlled trial of androgen deprivation therapy with or without docetaxel in high-risk biochemically recurrent prostate cancer after surgery (TAX3503). Eur Urol Oncol. 2021;4:543\u201352.","journal-title":"Eur Urol Oncol"},{"key":"894_CR16","doi-asserted-by":"publisher","first-page":"e1191","DOI":"10.1097\/JU.0000000000003361.11","volume":"209","author":"R Aggarwal","year":"2023","unstructured":"Aggarwal R, Eggener S, Heller G, Xiao H, Hillman D, Picus J, et al. LBA02-11\u2003Updated progression-free survival from PRESTO: a phase 3 randomized study of androgen annihilation for high-risk biochemically relapsed prostate cancer (AFT-19). J Urol. 2023;209:e1191.","journal-title":"J Urol"}],"container-title":["Prostate Cancer and Prostatic Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41391-024-00894-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41391-024-00894-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41391-024-00894-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T22:34:34Z","timestamp":1757111674000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41391-024-00894-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,13]]},"references-count":16,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["894"],"URL":"https:\/\/doi.org\/10.1038\/s41391-024-00894-0","relation":{},"ISSN":["1365-7852","1476-5608"],"issn-type":[{"value":"1365-7852","type":"print"},{"value":"1476-5608","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,13]]},"assertion":[{"value":"20 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 September 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 September 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"SJF reports consulting for Astellas Pharma Inc., AstraZeneca, Bayer, Eli Lilly, Exact Sciences, Janssen, Merck, Pfizer Inc., Sanofi, and Sumitomo Pharma America Inc. (formerly Myovant Sciences Inc). WG, AL, and HY are employees of Analysis Group. KR, DR, and JII own stocks or stock options\u00a0in\u00a0and are employees of Pfizer Inc., a study sponsor. AH is an employee of Pfizer Inc., a study sponsor, and owns stock in Veru, Revance, and Insmed.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This study was conducted in accordance with legal and regulatory requirements, as well as with scientific purpose, value and rigor and followed generally accepted research practices described in Guidelines for Good Pharmacoepidemiology Practices issued by the International Society for Pharmacoepidemiology.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}]}}