Evidence map›Paper›PMID 39663356›Full record

Trial reportNature communications2024

AR alterations inform circulating tumor DNA detection in metastatic castration resistant prostate cancer patients.

Todd P Knutson, Bin Luo, Anna Kobilka, Jacqueline Lyman, Siyuan Guo, Sarah A Munro, Yingming Li, Rakesh Heer, Luke Gaughan, Michael J Morris and 6 more

Abstract readRandomized Controlled TrialClinical Trial, Phase III
In one paragraph

Trial report in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Evolution of AR and Non-AR Alterations in ctDNA of Patients with Metastatic Prostate Cancer Treated in the Phase III Alliance A031201 Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Trial
  5. Review
  6. Review
  7. Review
  8. AR and Beyond: ctDNA Maps Resistance Evolution in mCRPC.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Todd P Knutson *Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN, USA.ORCID 0000-0001-8431-9964
Bin Luo *Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.ORCID 0000-0002-3983-5676
Anna KobilkaMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Jacqueline LymanMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Siyuan GuoDepartment of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
Sarah A MunroMinnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN, USA.
Yingming LiMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Rakesh HeerNewcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, Tyne and Wear, UK.
Luke GaughanTranslational and Clinical Research Institute, NU Cancer, Newcastle upon Tyne, Tyne and Wear, UK.
Michael J MorrisGenitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-9454-0096
Himisha BeltranDepartment of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-3259-2226
Charles J RyanMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Emmanuel S AntonarakisMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.ORCID 0000-0003-3531-3851
Andrew J ArmstrongDepartment of Medicine, Division of Medical Oncology, Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA.ORCID 0000-0001-7012-1754
Susan HalabiDepartment of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.ORCID 0000-0003-4135-2777
Scott M DehmMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA. dehm@umn.edu.ORCID 0000-0002-7827-5579

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Member Site CoreU10CA180821 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Evanthia Galanis, Olwen Hahn · 2014 to 2026
$177.3M
Statistics CoreU10CA180882 · NCI · MAYO CLINIC ROCHESTER · PI Sumithra Jay Mandrekar · 2014 to 2026
$115.0M
Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Timothy C. Hallstrom · 1998 to 2026
$100.4M
Network Lead Academic Participating Site: Memorial Sloan Kettering Cancer CenterUG1CA233290 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI CAROL AGHAJANIAN, Darren Feldman · 2019 to 2026
$10.2M
NCTN Lead Academic Participating Site at Dana-Farber/Partners Cancer CareUG1CA233180 · NCI · DANA-FARBER CANCER INST · PI Harold John Burstein · 2019 to 2026
$8.6M
AR Gene Rearrangements and AR Signaling in Prostate CancerR01CA174777 · NCI · UNIVERSITY OF MINNESOTA · PI Scott M. Dehm · 2013 to 2026
$4.9M
Molecular mechanisms underlying lineage plasticity in prostate cancerR37CA241486 · NCI · DANA-FARBER CANCER INST · PI Himisha Beltran · 2020 to 2026
$4.1M
The Duke University - Duke Cancer Institute National Clinical Trials Network LAPS (UG1) Support GrantUG1CA233253 · NCI · DUKE UNIVERSITY · PI John H Strickler, Alexandra Thomas · 2019 to 2026
$3.7M
Clinical genomic predictive model of first line androgen receptor inhibitor therapy outcomes in men with mCRPCR01CA256157 · NCI · DUKE UNIVERSITY · PI ARMSTRONG, ANDREW J, DEHM, SCOTT M. · 2020 to 2025
$3.2M
Targeting early events in prostate cancer lineage plasticityR01CA270539 · NCI · UNIVERSITY OF MINNESOTA · PI Scott M. Dehm · 2023 to 2026
$1.8M
NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA077598NCI NIH HHS R01 CA174777NCI NIH HHS R01 CA256157NCI NIH HHS R01 CA270539NCI NIH HHS R37 CA241486NCI NIH HHS U10 CA180821NCI NIH HHS U10 CA180882NCI NIH HHS UG1 CA233180NCI NIH HHS UG1 CA233253NCI NIH HHS UG1 CA233290Prostate Cancer Foundation (PCF) 18CHAL11U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA174777U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA256157U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA270539
6 · The paper itself

Abstract

Circulating tumor DNA (ctDNA) in plasma cell free DNA (cfDNA) of cancer patients is associated with poor prognosis, but is challenging to detect from low plasma volumes. In metastatic castration-resistant prostate cancer (mCRPC), ctDNA assays are needed to prognosticate outcomes of patients treated with androgen receptor (AR) inhibitors. We develop a custom targeted cfDNA sequencing assay, named AR-ctDETECT, to detect ctDNA in limiting plasma cfDNA available from mCRPC patients in the Alliance A031201 randomized phase 3 trial of enzalutamide with or without abiraterone. Of 776 patients, 59% are ctDNA-positive, with 26% having high ctDNA aneuploidy and 33% having low ctDNA aneuploidy but displaying AR gain or structural rearrangement, MYC/MYCN gain, or a pathogenic mutation. ctDNA-positive patients have significantly worse median overall survival than ctDNA-negative patients (29.0 months vs. 47.4 months, respectively). Here, we show that mCRPC patients identified as ctDNA-positive using the AR-ctDETECT assay have poor survival despite treatment with potent AR inhibitors in a phase 3 trial.

Indexed as

BenzamidesCirculating Tumor DNAPhenylthiohydantoinProstatic Neoplasms, Castration-ResistantReceptors, AndrogenAgedAndrostenesAneuploidyBiomarkers, TumorHumansMaleMiddle AgedMutationNeoplasm MetastasisNitrilesPrognosisabirateroneAndrostenesAR protein, humanBenzamidesBiomarkers, TumorCirculating Tumor DNAenzalutamideNitrilesPhenylthiohydantoinReceptors, Androgen

Identifiers

PMID39663356
PMCPMC11634963

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.