Evidence map›Paper›PMID 37932350›Full record

ArticleScientific reports2023

Impact of germline DNA repair gene variants on prognosis and treatment of men with advanced prostate cancer.

Emma B Hansen, Questa Karlsson, Susan Merson, Sarah Wakerell, Reshma Rageevakumar, Jørgen B Jensen, Michael Borre, Zsofia Kote-Jarai, Rosalind A Eeles, Karina D Sørensen

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.6field-weighted citation impact, top 15% 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

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
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

10 authors at 4 institutions in 2 countries.

Emma B HansenDepartment of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus, Denmark.
Questa KarlssonDivision of Genetics & Epidemiology, The Institute of Cancer Research, London, UK.
Susan MersonDivision of Genetics & Epidemiology, The Institute of Cancer Research, London, UK.
Sarah WakerellDivision of Genetics & Epidemiology, The Institute of Cancer Research, London, UK.
Reshma RageevakumarDivision of Genetics & Epidemiology, The Institute of Cancer Research, London, UK.
Jørgen B JensenDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Michael BorreDepartment of Urology, Aarhus University Hospital, Aarhus, Denmark.
Zsofia Kote-JaraiDivision of Genetics & Epidemiology, The Institute of Cancer Research, London, UK.
Rosalind A EelesDivision of Genetics & Epidemiology, The Institute of Cancer Research, London, UK.ORCID 0000-0002-3698-6241
Karina D SørensenDepartment of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus, Denmark. kdso@clin.au.dk.ORCID 0000-0002-4902-5490
Institute of Cancer Research · GBAarhus University · DKAarhus University Hospital · DKRoyal Marsden NHS Foundation Trust · GB

Funding

Cancer Research UK
6 · The paper itself

Abstract

The clinical importance of germline variants in DNA repair genes (DRGs) is becoming increasingly recognized, but their impact on advanced prostate cancer prognosis remains unclear. A cohort of 221 newly diagnosed metastatic castration-resistant prostate cancer (mCRPC) patients were screened for pathogenic germline variants in 114 DRGs. The primary endpoint was progression-free survival (PFS) on first-line androgen signaling inhibitor (ARSI) treatment for mCRPC. Secondary endpoints were time to mCRPC progression on initial androgen deprivation therapy (ADT) and overall survival (OS). Twenty-seven patients (12.2%) carried a germline DRG variant. DRG carrier status was independently associated with shorter PFS on first-line ARSI [HR 1.72 (1.06-2.81), P = 0.029]. At initiation of ADT, DRG carrier status was independently associated with shorter progression time to mCRPC [HR 1.56, (1.02-2.39), P = 0.04] and shorter OS [HR 1.99, (1.12-3.52), P = 0.02]. Investigating the contributions of individual germline DRG variants on PFS and OS revealed CHEK2 variants to have little effect. Furthermore, prior taxane treatment was associated with worse PFS on first-line ARSI for DRG carriers excluding CHEK2 (P = 0.0001), but not for noncarriers. In conclusion, germline DRG carrier status holds independent prognostic value for predicting advanced prostate cancer patient outcomes and may potentially inform on optimal treatment sequencing already at the hormone-sensitive stage.

Indexed as

Antineoplastic AgentsProstatic Neoplasms, Castration-ResistantAndrogen AntagonistsAndrogensDNA RepairHumansMalePrognosisTreatment OutcomeAndrogen AntagonistsAndrogensAntineoplastic Agents

Identifiers

PMID37932350
PMCPMC10628129
OpenAlexW4388421491

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.