{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:52:39Z","timestamp":1792511559730,"version":"4.5.0"},"reference-count":11,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec id=\"ab-zoi261072-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>In metastatic hormone-sensitive prostate cancer (mHSPC), randomized clinical trials directly comparing androgen deprivation therapy intensification using androgen synthesis inhibitors (ASIs) vs next-generation androgen receptor inhibitors (ARIs) are lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi261072-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To compare the outcomes associated with ASI vs ARI intensification therapy among patients with mHSPC in community or academic clinical practices.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi261072-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>This was a retrospective cohort study of patients diagnosed with mHSPC between February 4, 2013, and April 29, 2024, with follow-up through the July 2024 data cut, providing a median (IQR) follow-up of 25.6 (24.5-26.6) months. Patient-level data were extracted from the nationwide US-based Flatiron Health electronic health record\u2013derived deidentified research database of community and academic practices. Patients with evidence of an mHSPC diagnosis initiating treatment with an ASI (abiraterone acetate) or ARI (apalutamide or enzalutamide) within 3 months prior to or 6 months after an mHSPC diagnosis were eligible. Patients with prior docetaxel receipt were excluded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi261072-7\">\n                    <jats:title>Exposure<\/jats:title>\n                    <jats:p>Treatment with an ASI vs an ARI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi261072-8\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>The primary outcome was overall survival (OS), defined as time in months from mHSPC diagnosis to death or censoring at last recorded activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi261072-9\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 3404 patients (median [IQR] age, 73 [66-80] years), 1830 received treatment with an ASI (abiraterone), and 1574 with an ARI (507 apalutamide, 1067 enzalutamide). Following inverse probability of treatment weighting, patients receiving an ARI had significantly longer OS (median, 67.9 months [95% CI, 67.5 months to not reached]) compared with patients treated with the ASI (median, 57.2 months [95% CI, 52.7-63.3 months]) (hazard ratio [HR], 0.74 [95% CI, 0.64-0.87]);\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001). Results were similar in sensitivity analyses using therapy initiation as the index date (HR, 0.73 [95% CI, 0.62-0.84];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001) and when restricted to index dates on or after December 16, 2019 (HR, 0.67 [95% CI, 0.56-0.81];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001). The association was not modified by insurance status or socioeconomic status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi261072-10\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>In this cohort study of 3404 patients with mHSPC, treatment intensification with an ARI was associated with significantly longer OS compared with an ASI. These findings may help guide clinical treatment selection and patient counseling. However, given conflicting clinical practice data across differing database populations, only a randomized clinical trial can definitively answer this question.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.39458","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:30:22Z","timestamp":1792510222000},"page":"e2639458","source":"Crossref","is-referenced-by-count":0,"title":["Androgen Synthesis Inhibitors vs Androgen Receptor Inhibitors and Survival in Metastatic Hormone-Sensitive Prostate Cancer"],"prefix":"10.1001","volume":"9","author":[{"given":"Georges","family":"Gebrael","sequence":"first","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeonjung","family":"Jo","sequence":"additional","affiliation":[{"name":"Cancer Biostatistics, Huntsman Cancer Institute, University of Utah, Salt Lake City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varun","family":"Nandakumar","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynep Irem","family":"Ozay","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Mercinelli","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS San Raffaele Hospital, Comprehensive Cancer Center, Milan, Italy"},{"name":"Vita-Salute San Raffaele University, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Hooper","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micah","family":"Ostrowski","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Sayegh","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City"},{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishnam","family":"Goel","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, University of Kansas Cancer Center, Kansas City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinay Mathew","family":"Thomas","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumati","family":"Gupta","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avirup","family":"Guha","sequence":"additional","affiliation":[{"name":"Cardio-Oncology Program, Medical College of Georgia at Augusta University, Augusta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irbaz Bin","family":"Riaz","sequence":"additional","affiliation":[{"name":"Mayo Clinic, Phoenix, Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeraj","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umang","family":"Swami","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2026,10,20]]},"reference":[{"issue":"16","key":"zoi261072r1","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1001\/jama.2025.0228","article-title":"Prostate cancer: a review.","volume":"333","author":"Raychaudhuri","year":"2025","journal-title":"JAMA"},{"issue":"4","key":"zoi261072r2","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1056\/NEJMoa1702900","article-title":"Abiraterone for prostate cancer not previously treated with hormone therapy.","volume":"377","author":"James","year":"2017","journal-title":"N Engl J 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metastatic hormone-sensitive prostate cancer: a public-payer perspective.","volume":"115","author":"Yoo","year":"2023","journal-title":"J Natl Cancer Inst"},{"key":"zoi261072r9","unstructured":"Comparison of population characteristics in real-world clinical oncology databases in the US: Flatiron Health, SEER, and NPCR. Flatiron. Accessed July 14, 2026. https:\/\/resources.flatiron.com\/publications\/comparison-population-characteristics-oncology-databases-seer-npcr-flatironhealth"},{"key":"zoi261072r10","unstructured":"R: The R Project for Statistical Computing. Accessed July 14, 2026. https:\/\/www.r-project.org\/"},{"key":"zoi261072r11","unstructured":"Real-world comparative outcomes of abiraterone vs enzalutamide in metastatic castration-sensitive prostate cancer (mCSPC): a propensity-matched analysis from the TriNetX Global Health Research Network. American Society of Clinical Oncology. 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