Evidence map›Paper›PMID 29439820›Full record

Observational studyEuropean urology2018

Germline DNA-repair Gene Mutations and Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Receiving First-line Abiraterone and Enzalutamide.

Emmanuel S Antonarakis, Changxue Lu, Brandon Luber, Chao Liang, Hao Wang, Yan Chen, John L Silberstein, Danilo Piana, Zhao Lai, Yidong Chen and 2 more

Open access · greenAbstract readComparative StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in European urology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed, 5 pooled it
19.6field-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.

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

97 citing papers in PubMed, 5 syntheses or guidelines pooled it, 176 citations in OpenAlex.

  1. Pooled it
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  6. Trial
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  14. Article
  15. Prognostic Significance ofJCO precision oncology · 2025
    Article
  16. Review
  17. Review
  18. Review
  19. Germline DNA Damage Repair Variants and Prognosis of Patients with High-Risk or Metastatic Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Article
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Emmanuel S AntonarakisDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: eantona1@jhmi.edu.
Changxue LuDepartment of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Brandon LuberDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Chao LiangDepartment of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Hao WangDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Yan ChenDepartment of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
John L SilbersteinDepartment of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Danilo PianaDepartment of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Zhao LaiGreehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Yidong ChenGreehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
William B IsaacsDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jun LuoDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: jluo1@jhmi.edu.
Johns Hopkins Medicine · USJohns Hopkins University · USThe University of Texas Health Science Center at San Antonio · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
TRANSGENIC MODELS FOR PROSTATE CANCER AND AUTOIMMUNITYP50CA058236 · NCI · JOHNS HOPKINS UNIVERSITY · PI DENMEADE, SAMUEL R · 1992 to 2020
$43.9M
The aberrant androgen receptor underlies abiraterone/enzalutamide resistanceR01CA185297 · NCI · JOHNS HOPKINS UNIVERSITY · PI ANTONARAKIS, EMMANUEL S., LUO, JUN · 2015 to 2018
$1.5M
NCI NIH HHS P30 CA006973NCI NIH HHS P50 CA058236NCI NIH HHS R01 CA185297
6 · The paper itself

Abstract

backgroundInherited DNA-repair gene mutations are more prevalent in men with advanced prostate cancer than previously thought, but their clinical implications are not fully understood.

objectiveTo investigate the clinical significance of germline DNA-repair gene alterations in men with metastatic castration-resistant prostate cancer (mCRPC) receiving next-generation hormonal therapy (NHT), with a particular emphasis on BRCA/ATM mutations. DESIGN, SETTING, AND

participantsWe interrogated 50 genes for pathogenic or likely pathogenic germline mutations using leukocyte DNA from 172 mCRPC patients beginning treatment with first-line NHT with abiraterone or enzalutamide. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed the impact of germline DNA-repair gene mutation status on ≥50% and ≥90% PSA responses, PSA progression-free survival (PSA-PFS), clinical/radiologic progression-free survival (PFS), and overall survival (OS). Survival outcomes were adjusted using propensity score-weighted multivariable Cox regression analyses. RESULTS AND LIMITATIONS: Among 172 mCRPC patients included, germline mutations (in any DNA-repair gene) were found in 12% (22/172) of men, and germline BRCA/ATM mutations specifically in 5% (9/172) of men. In unadjusted analyses, outcomes to first-line NHT were better in men with germline BRCA/ATM mutations (vs no mutations) with respect to PSA-PFS (hazard ratio [HR] 0.47; p=0.061), PFS (HR 0.50; p=0.090), and OS (HR 0.28; p=0.059). In propensity score-weighted multivariable analyses, outcomes were superior in men with germline BRCA/ATM mutations with respect to PSA-PFS (HR 0.48, 95% confidence interval [CI] 0.25-0.92; p=0.027), PFS (HR 0.52, 95% CI 0.28-0.98; p=0.044), and OS (HR 0.34, 95% CI 0.12-0.99; p=0.048), but not in men with non-BRCA/ATM germline mutations (all p>0.10). These results require prospective validation, and our conclusions are limited by the small number of patients (n=9) with BRCA/ATM mutations.

conclusionsOutcomes to first-line NHT appear better in mCRPC patients harboring germline BRCA/ATM mutations (vs no mutations), but not for patients with other non-BRCA/ATM germline mutations. PATIENT SUMMARY: Patients with metastatic castration-resistant prostate cancer and harboring germline mutations in BRCA1/2 and ATM benefit from treatment with abiraterone and enzalutamide.

Indexed as

Germ-Line MutationAgedAndrogen AntagonistsAndrostenesAntigens, NeoplasmAntineoplastic Combined Chemotherapy ProtocolsAtaxia Telangiectasia Mutated ProteinsBenzamidesBiomarkers, TumorBRCA1 ProteinBRCA2 ProteinClinical Decision-MakingDNA Mutational AnalysisDNA Repair EnzymesGenetic Predisposition to DiseaseGPI-Linked ProteinsabirateroneAndrogen AntagonistsAndrostenesAntigens, NeoplasmAtaxia Telangiectasia Mutated ProteinsATM protein, humanBenzamidesBiomarkers, TumorBRCA1 ProteinBRCA1 protein, humanBRCA2 ProteinBRCA2 protein, humanDNA Repair EnzymesenzalutamideGPI-Linked ProteinsNeoplasm ProteinsNitrilesPhenylthiohydantoinPSCA protein, humanAbirateroneDNA repairEnzalutamideGermlineMutation

Identifiers

PMID29439820
PMCPMC6045965
OpenAlexW2786529129

What OpenQuestion holds

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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.