Evidence map›Paper›PMID 32268276›Full record

ArticleEBioMedicine2020

Clinical and genomic insights into circulating tumor DNA-based alterations across the spectrum of metastatic hormone-sensitive and castrate-resistant prostate cancer.

Manish Kohli, Winston Tan, Tiantian Zheng, Amy Wang, Carlos Montesinos, Calven Wong, Pan Du, Shidong Jia, Siddhartha Yadav, Lisa G Horvath and 5 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 78 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 2 pooled it
10.3field-weighted citation impact, top 1% of its field
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

78 citing papers in PubMed, 2 syntheses or guidelines pooled it, 132 citations in OpenAlex.

  1. Pooled it
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  10. Emerging Therapeutic Strategies in Metastatic Hormone-Sensitive Prostate Cancer.Journal of immunotherapy and precision oncology · 2026
    Review
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  19. Association of Homologous Recombination Repair Alterations with Outcomes in Patients with Metastatic Hormone-Sensitive Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Article
  20. Article

18 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 7 institutions in 2 countries.

Manish KohliDivision of Medical Oncology, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope Drive, Salt Lake City, UT 84112, United States. Electronic address: Manish.Kohli@hci.utah.edu.
Winston TanDepartment of Oncology, Mayo Clinic, Jacksonville, FL, United States.
Tiantian ZhengPredicine, Inc., Hayward, CA, United States.
Amy WangPredicine, Inc., Hayward, CA, United States.
Carlos MontesinosPredicine, Inc., Hayward, CA, United States.
Calven WongPredicine, Inc., Hayward, CA, United States.
Pan DuPredicine, Inc., Hayward, CA, United States.
Shidong JiaPredicine, Inc., Hayward, CA, United States.
Siddhartha YadavDepartment of Oncology, Mayo Clinic, Rochester, MN, United States.
Lisa G HorvathMedical Oncology, Chris O'Brien Lifehouse, Australia; Royal Prince Alfred Hospital, Australia; University of Sydney, Australia; Garvan Institute for Medical Research, Australia.
Kate L MahonMedical Oncology, Chris O'Brien Lifehouse, Australia; Royal Prince Alfred Hospital, Australia; University of Sydney, Australia; Garvan Institute for Medical Research, Australia.
Edmond M KwanDepartment of Medicine, School of Clinical Sciences, Monash University, Australia; Department of Medical Oncology, Monash Health, Australia.
Heidi FettkeDepartment of Medicine, School of Clinical Sciences, Monash University, Australia.
Jianjun YuPredicine, Inc., Hayward, CA, United States.
Arun A AzadDepartment of Medicine, School of Clinical Sciences, Monash University, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Australia.
The University of Sydney · AUMayo Clinic in Arizona · USMonash Medical Centre · AUMonash University · AUThe University of Melbourne · AUUniversity of Utah · USWinnMed · US

Funding

Cell free nucleic acid-based biomarkers in advanced prostate cancerR01CA212097 · NCI · MEDICAL COLLEGE OF WISCONSIN · PI KOHLI, MANISH, WANG, LIANG · 2017 to 2022
$3.1M
NCI NIH HHS R01 CA212097
6 · The paper itself

Abstract

backgroundMetastatic prostate cancer is a clonally heterogeneous disease state characterized by progressive somatic perturbations. The aim of this study was to identify cell free DNA- (cfDNA-) based alterations and their associations with outcomes in progressive metastatic prostate cancer.

methodsIn this longitudinal prospective cohort study plasma cfDNA/circulating tumor DNA (ctDNA) was analyzed before, during, and after androgen deprivation therapy (ADT) in 4 independent patient groups ranging from untreated metastatic hormone sensitive prostate cancer (mHSPC) to metastatic castrate resistant prostate cancer (mCRPC). Next generation sequencing was performed on ctDNA and germline DNA to characterize alterations and associations with clinical outcomes were determined for each group.

findingscfDNA yields were different in progressive mHSPC and mCRPC states (P < .001). In mHSPC, a higher than median ctDNA fraction was predictive of shorter time to ADT failure (HR, 2.29 [95% CI, 1.13-4.65]; Log-Rank P  =  .02). cfDNA, ctDNA taken with volume of metastatic disease in mHSPC and with alkaline phosphatase levels prognosticated survival better than clinical factors alone in mHSPC and mCRPC states (Log Rank P = 0.03). ctDNA-based AR, APC mutations were increased in mCRPC compared to mHSPC (P < ·05).TP53 mutations, RB1 loss, and AR gene amplifications correlated with poorer survival in mCRPC. Mutations in multiple DNA repair genes (ATM, BRCA1, BRCA2, CHEK2) were associated with time to ADT treatment failure and survival in mHSPC.

interpretationctDNA fraction can further refine clinical prognostic factors in metastatic prostate cancer. Somatic ctDNA alterations have potential prognostic, predictive, and therapeutic implications in metastatic prostate cancer management.

fundingSeveral funding sources have supported this study. A full list is provided in the Acknowledgments. No funding was received from Predicine, Inc. during the conduct of the study.

Indexed as

AgedAged, 80 and overAtaxia Telangiectasia Mutated ProteinsBiomarkers, TumorBRCA1 ProteinBRCA2 ProteinCheckpoint Kinase 2Circulating Tumor DNAHumansMaleMiddle AgedMutationNeoplasm MetastasisProstatic Neoplasms, Castration-ResistantReceptors, AndrogenRetinoblastoma Binding ProteinsAtaxia Telangiectasia Mutated ProteinsATM protein, humanBiomarkers, TumorBRCA1 ProteinBRCA1 protein, humanBRCA2 ProteinBRCA2 protein, humanCheckpoint Kinase 2CHEK2 protein, humanCirculating Tumor DNARB1 protein, humanReceptors, AndrogenRetinoblastoma Binding ProteinsTP53 protein, humanTumor Suppressor Protein p53Ubiquitin-Protein LigasesCirculating tumor DNAGenomic alterationsMetastatic prostate cancer

Identifiers

PMID32268276
PMCPMC7186589
OpenAlexW3014472365

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.