Evidence map›Paper›PMID 29206995›Full record

ArticleJournal of the National Cancer Institute2017

Concordance of Circulating Tumor DNA and Matched Metastatic Tissue Biopsy in Prostate Cancer.

Alexander W Wyatt, Matti Annala, Rahul Aggarwal, Kevin Beja, Felix Feng, Jack Youngren, Adam Foye, Paul Lloyd, Matti Nykter, Tomasz M Beer and 9 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the National Cancer Institute, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04015622 (A Randomized Phase II Trial Comparing Biomarker Directed Therapy Versus Clinician's Choice of Enzalutamide or Docetaxel in Patients With Advanced Prostate Cancer Post Abiraterone), which is not on this map. Cited by 238 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
238citing papers in PubMed, 9 pooled it
12.6field-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.

NCT04015622 phase2active not recruitingnot on this mapstarted 2020, after this paper: background citation

A Randomized Phase II Trial Comparing Biomarker Directed Therapy Versus Clinician's Choice of Enzalutamide or Docetaxel in Patients With Advanced Prostate Cancer Post Abiraterone

TypeinterventionalSponsorBritish Columbia Cancer AgencyRan2020 to 2026Enrolled100ConditionsMetastatic Castration-Resistant Prostate Cancer (mCRPC)ArmsEnzalutamide, Docetaxel
3 · Its place in the literature

Who cites it

238 citing papers in PubMed, 9 syntheses or guidelines pooled it, 411 citations in OpenAlex.

  1. Pooled it
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  5. Guideline
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  10. 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
  11. Trial
  12. PSMA+ Extracellular Vesicles Are a Biomarker for SABR in Oligorecurrent Prostate Cancer: Analysis from the STOMP-like and ORIOLE Trial Cohorts.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Trial
  13. Trial
  14. Trial
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  16. Phase II Multicenter Study of Enzalutamide in Metastatic Castration-Resistant Prostate Cancer to Identify Mechanisms Driving Resistance.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
    Trial
  17. Trial
  18. Trial
  19. Review
  20. Subclonal Complete Loss of CDKN1B as a Common Genomic Alteration in Prostate Cancer: Associations With Race and Prostate Cancer Outcomes.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2026
    Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 5 institutions in 3 countries.

Alexander W WyattDepartment of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; Oregon Health and Science University (OHSU) Knight Cancer Institute, Portland, OR; Department of Urology, University of California, Davis, School of Medicine, Sacremento, CA; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Matti AnnalaDepartment of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; Oregon Health and Science University (OHSU) Knight Cancer Institute, Portland, OR; Department of Urology, University of California, Davis, School of Medicine, Sacremento, CA; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Rahul AggarwalDepartment of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; Oregon Health and Science University (OHSU) Knight Cancer Institute, Portland, OR; Department of Urology, University of California, Davis, School of Medicine, Sacremento, CA; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Kevin BejaDepartment of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; Oregon Health and Science University (OHSU) Knight Cancer Institute, Portland, OR; Department of Urology, University of California, Davis, School of Medicine, Sacremento, CA; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Felix FengDepartment of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; Oregon Health and Science University (OHSU) Knight Cancer Institute, Portland, OR; Department of Urology, University of California, Davis, School of Medicine, Sacremento, CA; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Jack YoungrenDepartment of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; Oregon Health and Science University (OHSU) Knight Cancer Institute, Portland, OR; Department of Urology, University of California, Davis, School of Medicine, Sacremento, CA; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Adam FoyeDepartment of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; Oregon Health and Science University (OHSU) Knight Cancer Institute, Portland, OR; Department of Urology, University of California, Davis, School of Medicine, Sacremento, CA; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Paul LloydDepartment of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; Oregon Health and Science University (OHSU) Knight Cancer Institute, Portland, OR; Department of Urology, University of California, Davis, School of Medicine, Sacremento, CA; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Matti NykterDepartment of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; Oregon Health and Science University (OHSU) Knight Cancer Institute, Portland, OR; Department of Urology, University of California, Davis, School of Medicine, Sacremento, CA; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Tomasz M BeerDepartment of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; Oregon Health and Science University (OHSU) Knight Cancer Institute, Portland, OR; Department of Urology, University of California, Davis, School of Medicine, Sacremento, CA; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Joshi J AlumkalDepartment of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; Oregon Health and Science University (OHSU) Knight Cancer Institute, Portland, OR; Department of Urology, University of California, Davis, School of Medicine, Sacremento, CA; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
George V ThomasDepartment of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; Oregon Health and Science University (OHSU) Knight Cancer Institute, Portland, OR; Department of Urology, University of California, Davis, School of Medicine, Sacremento, CA; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Robert E ReiterDepartment of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; Oregon Health and Science University (OHSU) Knight Cancer Institute, Portland, OR; Department of Urology, University of California, Davis, School of Medicine, Sacremento, CA; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Matthew B RettigDepartment of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; Oregon Health and Science University (OHSU) Knight Cancer Institute, Portland, OR; Department of Urology, University of California, Davis, School of Medicine, Sacremento, CA; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Christopher P EvansDepartment of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; Oregon Health and Science University (OHSU) Knight Cancer Institute, Portland, OR; Department of Urology, University of California, Davis, School of Medicine, Sacremento, CA; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Allen C GaoDepartment of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; Oregon Health and Science University (OHSU) Knight Cancer Institute, Portland, OR; Department of Urology, University of California, Davis, School of Medicine, Sacremento, CA; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Kim N ChiDepartment of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; Oregon Health and Science University (OHSU) Knight Cancer Institute, Portland, OR; Department of Urology, University of California, Davis, School of Medicine, Sacremento, CA; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Eric J SmallDepartment of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; Oregon Health and Science University (OHSU) Knight Cancer Institute, Portland, OR; Department of Urology, University of California, Davis, School of Medicine, Sacremento, CA; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Martin E GleaveDepartment of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; Oregon Health and Science University (OHSU) Knight Cancer Institute, Portland, OR; Department of Urology, University of California, Davis, School of Medicine, Sacremento, CA; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Tampere University · FIOregon Health & Science University · USUniversity of British Columbia · CAUniversity of California, Davis · USTampere University · FI

Funding

UCLA SPORE IN PROSTATE CANCERP50CA092131 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREEMAN, MICHAEL R · 2002 to 2023
$42.6M
6 · The paper itself

Abstract

backgroundReal-time knowledge of the somatic genome can influence management of patients with metastatic castration-resistant prostate cancer (mCRPC). While routine metastatic tissue biopsy is challenging in mCRPC, plasma circulating tumor DNA (ctDNA) has emerged as a minimally invasive tool to sample the tumor genome. However, no systematic comparisons of matched "liquid" and "solid" biopsies have been performed that would enable ctDNA profiling to replace the need for direct tissue sampling.

methodsWe performed targeted sequencing across 72 clinically relevant genes in 45 plasma cell-free DNA (cfDNA) samples collected at time of metastatic tissue biopsy. We compared ctDNA alterations with exome sequencing data generated from matched tissue and quantified the concordance of mutations and copy number alterations using the Fisher exact test and Pearson correlations.

resultsSeventy-five point six percent of cfDNA samples had a ctDNA proportion greater than 2% of total cfDNA. In these patients, all somatic mutations identified in matched metastatic tissue biopsies were concurrently present in ctDNA. Furthermore, the hierarchy of variant allele fractions for shared mutations was remarkably similar between ctDNA and tissue. Copy number profiles between matched liquid and solid biopsy were highly correlated, and individual copy number calls in clinically actionable genes were 88.9% concordant. Detected alterations included AR amplifications in 22 (64.7%) samples, SPOP mutations in three (8.8%) samples, and inactivating alterations in tumor suppressors TP53 , PTEN , RB1 , APC , CDKN1B , BRCA2 , and PIK3R1 . In several patients, ctDNA sequencing revealed robust changes not present in paired solid biopsy, including clinically relevant alterations in the AR, WNT, and PI3K pathways.

conclusionsOur study shows that, in the majority of patients, a ctDNA assay is sufficient to identify all driver DNA alterations present in matched metastatic tissue and supports development of DNA biomarkers to guide mCRPC patient management based on ctDNA alone.

Indexed as

Adenomatous Polyposis Coli ProteinBiomarkers, TumorBRCA2 ProteinCirculating Tumor DNAClass Ia Phosphatidylinositol 3-KinaseCyclin-Dependent Kinase Inhibitor p27DNA Copy Number VariationsHumansLiquid BiopsyMaleMutationNeoplasm MetastasisNuclear ProteinsPhosphatidylinositol 3-KinasesProstatic Neoplasms, Castration-ResistantPTEN PhosphohydrolaseAdenomatous Polyposis Coli ProteinAPC protein, humanBiomarkers, TumorBRCA2 ProteinBRCA2 protein, humanCDKN1B protein, humanCirculating Tumor DNAClass Ia Phosphatidylinositol 3-KinaseCyclin-Dependent Kinase Inhibitor p27Nuclear ProteinsPhosphatidylinositol 3-KinasesPIK3R1 protein, humanPTEN PhosphohydrolasePTEN protein, humanRB1 protein, humanReceptors, AndrogenRepressor ProteinsRetinoblastoma Binding ProteinsSPOP protein, humanTP53 protein, humanTumor Suppressor Protein p53Ubiquitin-Protein Ligases

Identifiers

PMID29206995
PMCPMC6440274
OpenAlexW2725414935

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.