{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T20:17:39Z","timestamp":1788985059487,"version":"build-2803163510"},"reference-count":44,"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":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>There are few established prognostic biomarkers in metastatic hormone-sensitive prostate cancer (mHSPC). Disease volume and timing of metastases are prognostic and predictive factors but may be inadequate due to heterogeneity. Circulating tumor DNA (ctDNA) provides both circulating volume (tumor fraction [TF]) and genomic data. There are limited data on ctDNA in mHSPC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>This was a multicenter, prospective study of ctDNA testing in mHSPC. Presented here are the results before androgen-deprivation therapy initiation. The primary objective was to evaluate the association between TF and overall survival (OS) and time to mCRPC (TTCRPC). Secondary analyses included evaluating outcomes in subgroups of interest and key genomic subtypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Between 2018 and 2024, 85 patients were enrolled, of whom 72 (25% Black) had evaluable baseline ctDNA samples and are included herein. Baseline TF was positive in 46 patients (64%). Compared with patients with negative ctDNA TF, most patients with positive ctDNA TF had de novo (87%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      39%,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001) and high-volume disease (80%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      46%,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .01). At a median follow-up of 20.8 months, median OS was not reached (NR) with those with negative ctDNA TF and 33 months with positive ctDNA TF (hazard ratio [HR], 3.33 [95% CI, 1.1 to 9.9];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .03). However, a negative TF at baseline was associated with an undetectable 7-month prostate-specific antigen, a validated OS surrogate. Median TTCRPC was NR versus 13 months (HR, 3.43 [95% CI, 1.5 to 7.9];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .004). ctDNA TF was also potentially prognostic in high-volume disease and those who received doublet therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>In this diverse cohort, a positive ctDNA TF at baseline was associated with worse outcomes in mHSPC and may potentially complement current further risk stratification tools.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-01218","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T19:59:06Z","timestamp":1788983946000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Prospective Evaluation of Circulating Tumor DNA in Metastatic Hormone-Sensitive Prostate Cancer"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1898-5501","authenticated-orcid":true,"given":"Charles B.","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Medical Oncology &amp; Therapeutics Research, City of Hope Orange County, Irvine, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9105-8659","authenticated-orcid":true,"given":"Irene","family":"Tsung","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Rogel Cancer Center, University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4333-5092","authenticated-orcid":true,"given":"Jessica K.","family":"Lee","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Inc, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5461-9777","authenticated-orcid":true,"given":"Lincoln W.","family":"Pasquina","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Inc, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7340-2383","authenticated-orcid":true,"given":"Amy","family":"Kasputis","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Rogel Cancer Center, University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennie L.","family":"Lovett","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Rogel Cancer Center, University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8065-4148","authenticated-orcid":true,"given":"Ryon P.","family":"Graf","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Inc, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Redmond","sequence":"additional","affiliation":[{"name":"Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0075-3745","authenticated-orcid":true,"given":"Frank C.","family":"Cackowski","sequence":"additional","affiliation":[{"name":"Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1381-2713","authenticated-orcid":true,"given":"Elisabeth I.","family":"Heath","sequence":"additional","affiliation":[{"name":"Department of Oncology, Mayo Clinic Comprehensive Cancer Center, Rochester, 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