Evidence map›Paper›PMID 40774853›Full record

ArticleEuropean urology2026

Pathogenic Genomic Alterations in Circulating Tumor DNA Predict Overall Survival in Men with Metastatic Castrate-resistant Prostate Cancer.

Susan Halabi, Siyuan Guo, Bin Luo, Chenxi Yu, Todd P Knutson, Anna Kobilka, Jacqueline Lyman, Himisha Beltran, Emmanuel S Antonarakis, Matthew D Galsky and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European urology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–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

8 citing papers in PubMed.

  1. 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
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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

18 authors.

Susan HalabiDepartment of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, USA; Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC, USA. Electronic address: susan.halabi@duke.edu.
Siyuan GuoDepartment of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, USA.
Bin LuoDepartment of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, USA; Kennesaw State University, Marrietta, GA, USA.
Chenxi YuDepartment of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, USA.
Todd P KnutsonDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA; Department of Urology, University of Minnesota, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Anna KobilkaDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA; Department of Urology, University of Minnesota, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Jacqueline LymanDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA; Department of Urology, University of Minnesota, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Himisha BeltranDana-Farber Cancer Institute, Boston, MA, USA.
Emmanuel S AntonarakisDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA; Department of Urology, University of Minnesota, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Matthew D GalskyMount Sinai Medical Center, New York, NY, USA.
Jonathan E RosenbergMemorial Sloan Kettering Cancer Center, New York, NY, USA.
Charles J RyanMemorial Sloan Kettering Cancer Center, New York, NY, USA.
Eric J SmallUniversity of California San Francisco, San Francisco, CA, USA.
W Kevin KellyThomas Jefferson University, Philadelphia, PA, USA.
Michael J MorrisMemorial Sloan Kettering Cancer Center, New York, NY, USA.
David PageDepartment of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, USA.
Scott M DehmDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA; Department of Urology, University of Minnesota, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Andrew J ArmstrongDuke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC, USA; Department of Medicine, Division of Medical Oncology, Duke University, Durham, NC, USA.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Member Site CoreU10CA180821 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Evanthia Galanis · 2014 to 2026
$177.3M
Statistics CoreU10CA180882 · NCI · MAYO CLINIC ROCHESTER · PI Sumithra Jay Mandrekar · 2014 to 2026
$115.0M
THE ALLIANCE NCTN BIOREPOSITORY AND BIOSPECIMEN RESOURCEU24CA196171 · NCI · WASHINGTON UNIVERSITY · PI Mine Cicek, Wendy Frankel · 2015 to 2026
$35.0M
Molecular Determinants of Response and Resistance to EZH2 and PARP inhibition in Prostate CancerP50CA272390 · NCI · DANA-FARBER CANCER INST · PI Steven P. Balk, Himisha Beltran · 2023 to 2026
$12.0M
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
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
Interactions of Androgen Production, Uptake and Metabolism on outcome in Castration Resistant Prostate CancerR01CA249279 · NCI · UNIVERSITY OF MINNESOTA · PI HALABI, SUSAN, SHARIFI, NIMA · 2021 to 2024
$2.1M
FDA HHS U01 FD007857NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA272390NCI NIH HHS R01 CA174777NCI NIH HHS R01 CA249279NCI NIH HHS R01 CA256157NCI NIH HHS R37 CA241486NCI NIH HHS U10 CA180821NCI NIH HHS U10 CA180882NCI NIH HHS U24 CA196171
6 · The paper itself

Abstract

BACKGROUND AND

objectiveAlthough validated prognostic models exist for men with metastatic castration-resistant prostate cancer (mCRPC), current tools do not incorporate genomic biomarkers such as circulating tumor DNA (ctDNA) aneuploidy or pathogenic genetic alterations (PGAs). This study aimed to estimate the prevalence of PGAs in ctDNA, assess their correlation with ctDNA aneuploidy fraction, and evaluate their association with overall survival (OS). Additionally, we developed and validated a clinical-genetic (CG) model to predict OS.

methodsWe analyzed ctDNA from 776 patients enrolled in the Alliance phase 3 trial (A031201). PGAs were derived using the AR-ctDETECT assay. The net reclassification improvement (NRI) evaluated the added value of the CG model, and the time-dependent area under the receiver operating characteristic curve (tAUC) assessed the accuracy of the OS model. KEY FINDINGS AND LIMITATIONS: Feature selection using random survival forest identified gains in androgen receptor (AR), AR enhancer, MYC, RSPO2, CCND1, BRAF, and MET; losses or pathogenic variants in ZBTB16, PTEN, MSH6, PPP2R2A, NKX3-1, ZFHX3, TP53, ZNFR3, RB1, FANCA, CHECK1, APC, and CHD1; and a pathogenic AR variant. The CG model significantly outperformed the clinical model, with an average tAUC of 0.77 (95% confidence interval [CI]: 0.73-0.79) for the CG model compared with the tAUC of 0.72 (95% CI: 0.69-0.75, p = 0.01) for the clinical model, and NRI of 0.29 between the models. Patients were categorized by the predicted risk scores into poor-, intermediate-, and low-risk groups with median OS of 19.6, 33.6, and 60.8 mo, respectively. CONCLUSIONS AND CLINICAL IMPLICATIONS: Incorporation of PGAs from ctDNA into a CG model improved OS prediction by nearly 30% over a clinical model. This model can classify patients into risk groups and is useful for selecting patients in future mCRPC trials.

Indexed as

Biomarkers, TumorCirculating Tumor DNAProstatic Neoplasms, Castration-ResistantAgedHumansMaleMiddle AgedNeoplasm MetastasisPredictive Value of TestsPrognosisSurvival RateBiomarkers, TumorCirculating Tumor DNAAlterationsAR and non-AR pathogenic geneticCirculating tumor DNA tumor fractionMetastatic castration-resistant prostate cancerPrognostic model

Identifiers

PMID40774853
PMCPMC12645391

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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.