Evidence map›Paper›PMID 35871039›Full record

ArticleClinical genitourinary cancer2022

The Prognostic Significance of Homologous Recombination Repair Pathway Alterations in Metastatic Hormone Sensitive Prostate Cancer.

Aaron M Lee, Ava Saidian, Justin Shaya, Taylor Nonato, Angelo Cabal, J Michael Randall, Frederick Millard, Tyler Stewart, Brent Rose, Pablo Tamayo and 1 more

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

Article in Clinical genitourinary cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.9field-weighted citation impact, top 8% 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

14 citing papers in PubMed, 20 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Review
  4. Article
  5. Article
  6. Association of Homologous Recombination Repair Alterations with Outcomes in Patients with Metastatic Hormone-Sensitive Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. 2023 Canadian Urological Association guideline: Genetic testing in prostate cancer.Canadian Urological Association journal = Journal de l'Association des urologues du Canada · 2023
    Article
  13. Review
  14. 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

11 authors at 2 institutions in 1 country.

Aaron M LeeDepartment of Medicine, Division of Hematology-Oncology, University of California San Diego, La Jolla, CA.
Ava SaidianDepartment of Urology, University of California San Diego, La Jolla, CA.
Justin ShayaDepartment of Medicine, Division of Hematology-Oncology, University of California San Diego, La Jolla, CA.
Taylor NonatoDepartment of Medicine, Division of Hematology-Oncology, University of California San Diego, La Jolla, CA.
Angelo CabalDepartment of Medicine, Division of Hematology-Oncology, University of California San Diego, La Jolla, CA.
J Michael RandallDepartment of Medicine, Division of Hematology-Oncology, University of California San Diego, La Jolla, CA.
Frederick MillardDepartment of Medicine, Division of Hematology-Oncology, University of California San Diego, La Jolla, CA.
Tyler StewartDepartment of Medicine, Division of Hematology-Oncology, University of California San Diego, La Jolla, CA.
Brent RoseDepartment of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA.
Pablo TamayoDepartment of Medicine, Division of Hematology-Oncology, University of California San Diego, La Jolla, CA; Department of Urology, University of California San Diego, La Jolla, CA; Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA.
Rana R McKayDepartment of Medicine, Division of Hematology-Oncology, University of California San Diego, La Jolla, CA. Electronic address: rmckay@health.ucsd.edu.
University of California San Diego · USUC San Diego Health System · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
NCI NIH HHS P30 CA023100
6 · The paper itself

Abstract

introductionThe homologous recombination repair (HRR) pathway is a frequently mutated pathway in advanced prostate cancer. The clinical course of patients with HRR gene alterations who have metastatic hormone sensitive prostate cancer (mHSPC) has not been fully characterized. Here, we examine the outcomes of men with mHSPC with HRR alterations.

methodsWe conducted a single-center retrospective analysis of men with mHSPC who underwent next generation sequencing. The primary objective was to assess the time from diagnosis of mHSPC to metastatic castrate resistance prostate cancer (mCRPC) in patients with pathogenic HRR alterations compared to individuals lacking these alterations. Key secondary objectives included time to mCRPC in prespecified cohorts, PSA response, and overall survival.

results151 men with mHSPC were identified for the study. 24% (N = 37) had pathogenic HRR gene alterations detected with the most common alterations found in BRCA2 (n = 15), ATM (n = 10), and CDK12 (n = 7). Time to mCRPC was significantly decreased in patients with HRR gene alterations versus those without such alterations (12.7 vs. 16.1 months, HR 1.95, P = .02). In multivariate analysis, the effect of HRR gene alterations on time to CRPC remained significant when adjusting for age, mHSPC therapy, the volume of disease, the presence of visceral metastases, and PSA (adjusted HR 1.69, P = .02). Stratified by specific HRR gene alteration, patients with BRCA2 or CDK12 had significantly decreased time to mCRPC compared to other HRR alterations.

conclusionHRR gene alterations are associated with the worse outcomes in mHSPC with significantly shorter time to mCRPC. Given the established role of Poly (ADP-ribose) Polymerase (PARP) inhibitors in mCRPC, these data highlight an opportunity to examine PARP inhibitors earlier in the clinical course for prostate cancer patients. Ongoing prospective studies will further validate the role of PARP inhibitors in mHSPC patients.

Indexed as

Prostatic Neoplasms, Castration-ResistantHormonesHumansMalePoly(ADP-ribose) Polymerase InhibitorsPrognosisProspective StudiesProstate-Specific AntigenRecombinational DNA RepairRetrospective StudiesHormonesPoly(ADP-ribose) Polymerase InhibitorsProstate-Specific AntigenBiomarkerBRCA2CDK12CRPCHRRPARP inhibitorsPSA

Identifiers

PMID35871039
PMCPMC10257153
OpenAlexW4283731880

What OpenQuestion holds

Textmetadata
LicenceTDM
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.