Genomic Testing in Localized Prostate Cancer Can Identify Subsets of African Americans With Aggressive Disease.


Journal

Journal of the National Cancer Institute
ISSN: 1460-2105
Titre abrégé: J Natl Cancer Inst
Pays: United States
ID NLM: 7503089

Informations de publication

Date de publication:
08 12 2022
Historique:
accepted: 23 08 2022
received: 21 02 2022
revised: 22 05 2022
pubmed: 3 9 2022
medline: 15 12 2022
entrez: 2 9 2022
Statut: ppublish

Résumé

Personalized genomic classifiers have transformed the management of prostate cancer (PCa) by identifying the most aggressive subsets of PCa. Nevertheless, the performance of genomic classifiers to risk classify African American men is thus far lacking in a prospective setting. This is a prospective study of the Decipher genomic classifier for National Comprehensive Cancer Network low- and intermediate-risk PCa. Study-eligible non-African American men were matched to African American men. Diagnostic biopsy specimens were processed to estimate Decipher scores. Samples accrued in NCT02723734, a prospective study, were interrogated to determine the genomic risk of reclassification (GrR) between conventional clinical risk classifiers and the Decipher score. The final analysis included a clinically balanced cohort of 226 patients with complete genomic information (113 African American men and 113 non-African American men). A higher proportion of African American men with National Comprehensive Cancer Network-classified low-risk (18.2%) and favorable intermediate-risk (37.8%) PCa had a higher Decipher score than non-African American men. Self-identified African American men were twice more likely than non-African American men to experience GrR (relative risk [RR] = 2.23, 95% confidence interval [CI] = 1.02 to 4.90; P = .04). In an ancestry-determined race model, we consistently validated a higher risk of reclassification in African American men (RR = 5.26, 95% CI = 1.66 to 16.63; P = .004). Race-stratified analysis of GrR vs non-GrR tumors also revealed molecular differences in these tumor subtypes. Integration of genomic classifiers with clinically based risk classification can help identify the subset of African American men with localized PCa who harbor high genomic risk of early metastatic disease. It is vital to identify and appropriately risk stratify the subset of African American men with aggressive disease who may benefit from more targeted interventions.

Sections du résumé

BACKGROUND
Personalized genomic classifiers have transformed the management of prostate cancer (PCa) by identifying the most aggressive subsets of PCa. Nevertheless, the performance of genomic classifiers to risk classify African American men is thus far lacking in a prospective setting.
METHODS
This is a prospective study of the Decipher genomic classifier for National Comprehensive Cancer Network low- and intermediate-risk PCa. Study-eligible non-African American men were matched to African American men. Diagnostic biopsy specimens were processed to estimate Decipher scores. Samples accrued in NCT02723734, a prospective study, were interrogated to determine the genomic risk of reclassification (GrR) between conventional clinical risk classifiers and the Decipher score.
RESULTS
The final analysis included a clinically balanced cohort of 226 patients with complete genomic information (113 African American men and 113 non-African American men). A higher proportion of African American men with National Comprehensive Cancer Network-classified low-risk (18.2%) and favorable intermediate-risk (37.8%) PCa had a higher Decipher score than non-African American men. Self-identified African American men were twice more likely than non-African American men to experience GrR (relative risk [RR] = 2.23, 95% confidence interval [CI] = 1.02 to 4.90; P = .04). In an ancestry-determined race model, we consistently validated a higher risk of reclassification in African American men (RR = 5.26, 95% CI = 1.66 to 16.63; P = .004). Race-stratified analysis of GrR vs non-GrR tumors also revealed molecular differences in these tumor subtypes.
CONCLUSIONS
Integration of genomic classifiers with clinically based risk classification can help identify the subset of African American men with localized PCa who harbor high genomic risk of early metastatic disease. It is vital to identify and appropriately risk stratify the subset of African American men with aggressive disease who may benefit from more targeted interventions.

Identifiants

pubmed: 36053178
pii: 6687132
doi: 10.1093/jnci/djac162
pmc: PMC9745424
doi:

Banques de données

ClinicalTrials.gov
['NCT02723734']

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1656-1664

Subventions

Organisme : NCI NIH HHS
ID : P20 CA233255
Pays : United States
Organisme : NIH HHS
ID : P20-CA233255
Pays : United States
Organisme : NIH HHS
ID : P30-CA076292
Pays : United States

Informations de copyright

Published by Oxford University Press 2022.

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Auteurs

Shivanshu Awasthi (S)

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

G Daniel Grass (GD)

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Javier Torres-Roca (J)

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Peter A S Johnstone (PAS)

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Julio Pow-Sang (J)

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Jasreman Dhillon (J)

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Jong Park (J)

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Robert J Rounbehler (RJ)

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Elai Davicioni (E)

Veracyte Inc, South San Francisco, CA, USA.

Alex Hakansson (A)

Veracyte Inc, South San Francisco, CA, USA.

Yang Liu (Y)

Veracyte Inc, South San Francisco, CA, USA.

Angelina K Fink (AK)

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Amanda DeRenzis (A)

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Jordan H Creed (JH)

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Michael Poch (M)

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Roger Li (R)

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Brandon Manley (B)

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Daniel Fernandez (D)

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Arash Naghavi (A)

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Kenneth Gage (K)

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Grace Lu-Yao (G)

Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, PA, USA.

Evangelia Katsoulakis (E)

James A. Haley Veterans Hospital, Tampa, FL, USA.

Ryan J Burri (RJ)

Bay Pines VA Healthcare System, Tampa, FL, USA.

Andrew Leone (A)

Bay Pines VA Healthcare System, Tampa, FL, USA.

Cesar E Ercole (CE)

James A. Haley Veterans Hospital, Tampa, FL, USA.

Joshua D Palmer (JD)

The James Cancer Hospital at Ohio State University, Columbus, OH, USA.

Neha Vapiwala (N)

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Curtiland Deville (C)

Johns Hopkins University, Baltimore, MD, USA.

Timothy R Rebbeck (TR)

Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Adam P Dicker (AP)

Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, PA, USA.

William Kelly (W)

Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, PA, USA.

Kosj Yamoah (K)

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

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