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

Author:

Awasthi Shivanshu1ORCID,Grass G Daniel1,Torres-Roca Javier1,Johnstone Peter A S1,Pow-Sang Julio1ORCID,Dhillon Jasreman1,Park Jong1,Rounbehler Robert J1,Davicioni Elai2,Hakansson Alex2,Liu Yang2,Fink Angelina K1,DeRenzis Amanda1,Creed Jordan H1,Poch Michael1,Li Roger1,Manley Brandon1,Fernandez Daniel1,Naghavi Arash1,Gage Kenneth1,Lu-Yao Grace3,Katsoulakis Evangelia4,Burri Ryan J5,Leone Andrew5,Ercole Cesar E4,Palmer Joshua D6,Vapiwala Neha7,Deville Curtiland8,Rebbeck Timothy R9ORCID,Dicker Adam P3,Kelly William3,Yamoah Kosj1ORCID

Affiliation:

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

2. Veracyte Inc , South San Francisco, CA, USA

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

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

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

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

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

8. Johns Hopkins University , Baltimore, MD, USA

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

Abstract

Abstract 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.

Funder

George Edgecomb Society; Cancer Center Support

Moffitt Cancer Center

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

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