Evidence map›Paper›PMID 37558543›Full record

ArticleEuropean urology oncology2024

Identification of a Predictive Genomic Biomarker for Prostate-directed Therapy in Synchronous Low-volume Metastatic Castration-sensitive Prostate Cancer.

Philip Sutera, Amol C Shetty, Yang Song, Theresa Hodges, Tung Hoang, Zaker Rana, Kenneth Pienta, Felix Feng, Daniel Y Song, Theodore DeWeese and 6 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European urology oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

6 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
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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 at 7 institutions in 4 countries.

Philip SuteraDepartment of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Amol C ShettyInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA.
Yang SongInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA.
Theresa HodgesInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA.
Tung HoangDepartment of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biochemistry and Molecular Biology, Johns Hopkins University, School of Public Health, Baltimore, MD, USA.
Zaker RanaDepartment of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA.
Kenneth PientaDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Felix FengDepartments of Medicine, Urology and Radiation Oncology, UCSF, San Francisco, CA, USA.
Daniel Y SongDepartment of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Theodore DeWeeseDepartment of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Silke GillessenIstituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland.
Christopher SweeneySouth Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, Australia.
Nicholas JamesThe Royal Marsden Hospital NHS Foundation Trust and The Institute of Cancer Research, London, UK.
Gerhardt AttardDivision of Molecular Pathology, The Institute of Cancer Research, London, UK.
Matthew DeekDepartment of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA.
Phuoc T TranDepartment of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: phuoc.tran@som.umaryland.edu.
Johns Hopkins University · USUniversity of Maryland, Baltimore · USInstitute of Cancer Research · GBCentre for Cancer Biology · AURutgers, The State University of New Jersey · USUniversità della Svizzera italiana · CHUniversity of California, San Francisco · US

Funding

Resource Sharing CoreU54CA273956 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI Phuoc T. Tran · 2022 to 2026
$8.9M
Tumor-barcoding coupled with high-throughput sequencing of a novel chemoradiation resistant SCLC mouse modelU01CA231776 · NCI · JOHNS HOPKINS UNIVERSITY · PI HANN, CHRISTINE L., MARCHIONNI, LUIGI · 2018 to 2022
$3.9M
Integrating bioinformatics into multiscale models for hepatocellular carcinomaU01CA212007 · NCI · JOHNS HOPKINS UNIVERSITY · PI EWALD, ANDREW JOSEF, FERTIG, ELANA · 2018 to 2022
$3.2M
Tumor-barcoding coupled with high-throughput sequencing for quantitative radiogenomics of the abscopal response in NSCLCR01CA271540 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Phuoc T. Tran · 2023 to 2026
$2.3M
NCI NIH HHS R01 CA271540NCI NIH HHS U01 CA212007NCI NIH HHS U01 CA231776NCI NIH HHS U54 CA273956
6 · The paper itself

Abstract

backgroundStandard of care management for synchronous metastatic castration-sensitive prostate cancer (mCSPC) includes androgen deprivation therapy with a second-generation antiandrogen therapy and/or docetaxel. Recently, randomized data have demonstrated that prostate-directed therapy (PDT) is associated with an improvement in overall survival (OS) among patients with low-volume metastatic disease. Tumor genomics represents an additional dimension to define the clinical trajectory of patients with mCSPC.

objectiveTo evaluate a high-risk (HiRi) genomic signature to predict the benefit from PDT. DESIGN, SETTING, AND

participantsWe performed a single-institution retrospective review of men with synchronous low-volume mCSPC who underwent DNA panel sequencing of their tumor. Patients were classified according to the presence of HiRi mutation including pathogenic mutations in TP53, ATM, BRCA1, BRCA2, or Rb1. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was to determine the effect of PDT on OS in patients with and without a HiRi mutation. A survival analysis was performed with the Kaplan-Meier method compared with log-rank test and multivariable Cox regression. The interaction between HiRi mutation and PDT was evaluated. RESULTS AND LIMITATIONS: A total of 101 patients with synchronous low-volume CSPC were included with a median follow-up of 44 mo. Approximately half of patients were found to have a HiRi pathogenic mutation (49%). Patients with HiRi mutations demonstrated median OS of 73 versus 66.8 mo (p = 0.3) for no PDT versus PDT. Conversely, patients without a HiRi mutation demonstrated a significant improvement in OS of 60 versus 105.3 mo (p < 0.001) for no PDT versus PDT. The p value for interaction for OS between PDT and HiRi mutation was statistically significant (p < 0.001). Limitations include the retrospective nature of the study.

conclusionsHere, we have identified a HiRi genomic biomarker that appears predictive for the lack of benefit from PDT in men with synchronous low-volume mCSPC. Further work validating these results is warranted. PATIENT SUMMARY: In this report, we evaluated a high-risk genomic biomarker to predict the benefit from prostate-directed therapy for men with synchronous low-volume metastatic castration-sensitive prostate cancer. We found that men without a high-risk mutation appear to experience a greater clinical benefit from prostate-directed therapy than those with a high-risk mutation.

Indexed as

Prostatic NeoplasmsAndrogen AntagonistsBiomarkers, TumorCastrationHumansMaleProstateRetrospective StudiesAndrogen AntagonistsBiomarkers, TumorCastration-sensitive prostate cancerGenomicsLow volumeProstate-directed therapy

Identifiers

PMID37558543
PMCPMC10850431
OpenAlexW4385660921

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.