Evidence map›Paper›PMID 36059000›Full record

Trial reportGenome medicine2022

Accumulation of copy number alterations and clinical progression across advanced prostate cancer.

Emily Grist, Stefanie Friedrich, Christopher Brawley, Larissa Mendes, Marina Parry, Adnan Ali, Aine Haran, Alex Hoyle, Claire Gilson, Sharanpreet Lall and 23 more

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Genome medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00268476 (STAMPEDE), which is not on this map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.6field-weighted citation impact, top 6% 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.

NCT00268476 phase2 / phase3active not recruitingnot on this map

STAMPEDE: Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy: A Multi-Stage Multi-Arm Randomised Controlled Trial

TypeinterventionalSponsorMedical Research CouncilRan2005 to 2030Enrolled11,992ConditionsProstate CancerArmsCelecoxib, Docetaxel, Prednisolone, ADT, Zoledronic Acid
3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 27 citations in OpenAlex.

  1. Trial
  2. Review
  3. Observational
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
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  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Triplet therapy for metastatic castration-sensitive prostate cancer: Rationale and clinical evidence.International journal of urology : official journal of the Japanese Urological Association · 2025
    Review
  17. Article
  18. Review
  19. Article
  20. Prostate Cancer Stem Cells: Biology and Treatment Implications.International journal of molecular sciences · 2023
    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

33 authors at 8 institutions in 2 countries.

Emily Grist *Cancer Institute, University College London, London, UK.
Stefanie Friedrich *Cancer Institute, University College London, London, UK.
Christopher BrawleyMRC Clinical Trials Unit at University College London, London, UK.
Larissa MendesCancer Institute, University College London, London, UK.
Marina ParryCancer Institute, University College London, London, UK.
Adnan AliGU Cancer Research/FASTMAN Group, Manchester Cancer Institute, Manchester, UK.
Aine HaranThe Christie and Salford Royal NHS Foundation Trusts, Manchester, UK.
Alex HoyleThe Christie and Salford Royal NHS Foundation Trusts, Manchester, UK.
Claire GilsonMRC Clinical Trials Unit at University College London, London, UK.
Sharanpreet LallCancer Institute, University College London, London, UK.
Leila ZakkaCancer Institute, University College London, London, UK.
Carla BautistaCancer Institute, University College London, London, UK.
Alex LandlessCancer Institute, University College London, London, UK.
Karolina NowakowskaCancer Institute, University College London, London, UK.
Anna WingateCancer Institute, University College London, London, UK.
Daniel WetterskogCancer Institute, University College London, London, UK.
A M Mahedi HasanCancer Institute, University College London, London, UK.
Nafisah B AkatoMRC Clinical Trials Unit at University College London, London, UK.
Malissa RichmondMRC Clinical Trials Unit at University College London, London, UK.
Sofeya IshaqMRC Clinical Trials Unit at University College London, London, UK.
Nik Matthews *The Institute of Cancer Research, London, UK.
Anis A HamidDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Christopher J SweeneyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Matthew R SydesMRC Clinical Trials Unit at University College London, London, UK.
Daniel M BerneyBarts Cancer Institute, Queen Mary University of London, London, UK.
Stefano LiseCancer Institute, University College London, London, UK.
STAMPEDE investigators
Mahesh K B ParmarMRC Clinical Trials Unit at University College London, London, UK.
Noel W ClarkeGU Cancer Research/FASTMAN Group, Manchester Cancer Institute, Manchester, UK.
Nicholas D JamesThe Royal Marsden Hospital NHS Foundation Trust and The Institute of Cancer Research, London, UK.
Paolo Cremaschi *Cancer Institute, University College London, London, UK.
Louise C Brown *MRC Clinical Trials Unit at University College London, London, UK.
Gerhardt Attard *Cancer Institute, University College London, London, UK. g.attard@ucl.ac.uk.
University College London · GBMRC Clinical Trials Unit at UCL · GBInstitute of Cancer Research · GBDana-Farber Cancer Institute · USSalford Royal NHS Foundation Trust · GBCancer Research UK · GBCancer Research UK Manchester Institute · GBQueen Mary University of London · GB

Funding

Comprehensive genomic profiling of aggressive hormone sensitive prostate cancerR01CA238020 · NCI · UNIVERSITY OF ADELAIDE · PI SWEENEY, CHRISTOPHER J · 2020 to 2025
$2.5M
Cancer Research UK 3804Cancer Research UK A22744Cancer Research UK A27436Medical Research Council MC_UU_00004/01Medical Research Council MC_UU_00004/02Medical Research Council MC_UU_12023/20Medical Research Council MC_UU_12023/25NCI NIH HHS R01 CA238020NIH HHS R01CA238020Wellcome Trust
6 · The paper itself

Abstract

backgroundGenomic copy number alterations commonly occur in prostate cancer and are one measure of genomic instability. The clinical implication of copy number change in advanced prostate cancer, which defines a wide spectrum of disease from high-risk localised to metastatic, is unknown.

methodsWe performed copy number profiling on 688 tumour regions from 300 patients, who presented with advanced prostate cancer prior to the start of long-term androgen deprivation therapy (ADT), in the control arm of the prospective randomised STAMPEDE trial. Patients were categorised into metastatic states as follows; high-risk non-metastatic with or without local lymph node involvement, or metastatic low/high volume. We followed up patients for a median of 7 years. Univariable and multivariable Cox survival models were fitted to estimate the association between the burden of copy number alteration as a continuous variable and the hazard of death or disease progression.

resultsThe burden of copy number alterations positively associated with radiologically evident distant metastases at diagnosis (P=0.00006) and showed a non-linear relationship with clinical outcome on univariable and multivariable analysis, characterised by a sharp increase in the relative risk of progression (P=0.003) and death (P=0.045) for each unit increase, stabilising into more modest increases with higher copy number burdens. This association between copy number burden and outcome was similar in each metastatic state. Copy number loss occurred significantly more frequently than gain at the lowest copy number burden quartile (q=4.1 × 10

conclusionsCopy number alteration in advanced prostate cancer associates with increased risk of metastases at diagnosis. Accumulation of a limited number of copy number alterations associates with most of the increased risk of disease progression and death. The increased likelihood of involvement of specific segments in high copy number alteration burden cancers may suggest an order underlying the accumulation of copy number changes.

trial registrationClinicalTrials.gov NCT00268476 , registered on December 22, 2005. EudraCT  2004-000193-31 , registered on October 4, 2004.

Indexed as

Prostatic NeoplasmsAndrogen AntagonistsDisease ProgressionDNA Copy Number VariationsHumansMaleProspective StudiesAndrogen AntagonistsAdvanced prostate cancerCopy number alterationGenomic biomarkersSTAMPEDE trial

Identifiers

PMID36059000
PMCPMC9442998
OpenAlexW4294668777

What OpenQuestion holds

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LicenceCC BY
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.