Genomic Testing Reveals Distinct Mutation Patterns in Black and White Veterans With Metastatic Prostate Cancer

TOPLINE: Next-generation sequencing (NGS) analysis of 5015 veterans with metastatic prostate cancer reveals distinct genomic patterns between non-Hispanic Black and White patients, with Black veterans showing higher odds of immunotherapy targets but lower odds of androgen receptor axis alterations. However, the rates of survival were similar despite the differences.

METHODOLOGY: 
Researchers conducted a retrospective cohort study comparing alteration frequencies between 1784 non-Hispanic Black (35.6%) and 3,231 non-Hispanic White (64.4%) veterans who underwent NGS testing from January 23, 2019, to November 2, 2023.

•      Analysis included DNA sequencing data from tissue or plasma biospecimens, including prostate biopsy specimens, radical prostatectomy specimens, and prostate cancer metastases, all sequenced with FoundationOne CDx or FoundationOne Liquid CDx platforms.
•      Investigators examined pathogenic alterations in individual genes, actionable targets, and canonical prostate cancer pathways, while adjusting for NGS analyte and clinicopathologic covariates.
•      Researchers evaluated associations between alteration frequency and race as well as survival through Cox proportional hazards modeling, stratified by race and adjusted for clinical factors.

TAKEAWAY:
Non-Hispanic Black race and ethnicity was associated with higher odds of genomic alterations in SPOP (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.2-2.6) and immunotherapy targets (OR, 1.7; 95% CI, 1.1-2.5), including high microsatellite instability status (OR, 3.1; 95% CI, 1.1-9.4).

•      Non-Hispanic Black veterans showed lower odds of genomic alterations in the AKT/PI3K pathway (OR, 0.6; 95% CI, 0.4-0.7), androgen receptor axis (OR, 0.7; 95% CI, 0.5-0.9), and tumor suppressor genes (OR, 0.7; 95% CI, 0.5-0.8).
•      Tumor suppressor alterations were associated with shorter overall survival in both non-Hispanic Black (hazard ratio [HR], 1.54; 95% CI, 1.13-2.11) and non-Hispanic White (HR, 1.52; 95% CI, 1.25-1.85) veterans.
•      CDK12 alterations significantly increased the hazard of death in non-Hispanic Black veterans (HR, 2.04; 95% CI, 1.13-3.67), while immunotherapy targets were associated with increased mortality in non-Hispanic White veterans (HR, 1.44; 95% CI, 1.02-2.02).

IN PRACTICE: " we did not identify any genomic alterations or biomarkers that should not be tested in PCa based on patient self-identified race. Ultimately, this work emphasizes that precision oncology enables the individualization of treatment decisions without having to rely on imprecise characteristics such as self-identified race.," wrote the study authors.

SOURCE: Isla P. Garraway, MD, PhD; Kosj Yamoah, MD, PhD; and Kara N. Maxwell, MD, PhD were co-senior authors. The article was published online on May 12 in JAMA Network Open.

LIMITATIONS: According to the authors, a lack of matched germline data for patients, complicated the interpretation of plasma results. In addition, survivorship bias may have inadvertently excluded the most aggressive metastatic prostate cancer phenotypes, as patients who did not live long enough to undergo NGS testing were not included. Results seen in the veteran population served by the Veterans Health Administration may not be generalizable to the broader population.

DISCLOSURES: The study received support from Challenge Award PCF22CHALO2 from the Prostate Cancer Foundation and the Veterans Affairs National Precision Oncology Program. Luca F. Valle, MD, reported receiving grant support from the Bristol Myers Squibb Foundation during the conduct of the study. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE: Next-generation sequencing (NGS) analysis of 5015 veterans with metastatic prostate cancer reveals distinct genomic patterns between non-Hispanic Black and White patients, with Black veterans showing higher odds of immunotherapy targets but lower odds of androgen receptor axis alterations. However, the rates of survival were similar despite the differences.

METHODOLOGY: 
Researchers conducted a retrospective cohort study comparing alteration frequencies between 1784 non-Hispanic Black (35.6%) and 3,231 non-Hispanic White (64.4%) veterans who underwent NGS testing from January 23, 2019, to November 2, 2023.

•      Analysis included DNA sequencing data from tissue or plasma biospecimens, including prostate biopsy specimens, radical prostatectomy specimens, and prostate cancer metastases, all sequenced with FoundationOne CDx or FoundationOne Liquid CDx platforms.
•      Investigators examined pathogenic alterations in individual genes, actionable targets, and canonical prostate cancer pathways, while adjusting for NGS analyte and clinicopathologic covariates.
•      Researchers evaluated associations between alteration frequency and race as well as survival through Cox proportional hazards modeling, stratified by race and adjusted for clinical factors.

TAKEAWAY:
Non-Hispanic Black race and ethnicity was associated with higher odds of genomic alterations in SPOP (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.2-2.6) and immunotherapy targets (OR, 1.7; 95% CI, 1.1-2.5), including high microsatellite instability status (OR, 3.1; 95% CI, 1.1-9.4).

•      Non-Hispanic Black veterans showed lower odds of genomic alterations in the AKT/PI3K pathway (OR, 0.6; 95% CI, 0.4-0.7), androgen receptor axis (OR, 0.7; 95% CI, 0.5-0.9), and tumor suppressor genes (OR, 0.7; 95% CI, 0.5-0.8).
•      Tumor suppressor alterations were associated with shorter overall survival in both non-Hispanic Black (hazard ratio [HR], 1.54; 95% CI, 1.13-2.11) and non-Hispanic White (HR, 1.52; 95% CI, 1.25-1.85) veterans.
•      CDK12 alterations significantly increased the hazard of death in non-Hispanic Black veterans (HR, 2.04; 95% CI, 1.13-3.67), while immunotherapy targets were associated with increased mortality in non-Hispanic White veterans (HR, 1.44; 95% CI, 1.02-2.02).

IN PRACTICE: " we did not identify any genomic alterations or biomarkers that should not be tested in PCa based on patient self-identified race. Ultimately, this work emphasizes that precision oncology enables the individualization of treatment decisions without having to rely on imprecise characteristics such as self-identified race.," wrote the study authors.

SOURCE: Isla P. Garraway, MD, PhD; Kosj Yamoah, MD, PhD; and Kara N. Maxwell, MD, PhD were co-senior authors. The article was published online on May 12 in JAMA Network Open.

LIMITATIONS: According to the authors, a lack of matched germline data for patients, complicated the interpretation of plasma results. In addition, survivorship bias may have inadvertently excluded the most aggressive metastatic prostate cancer phenotypes, as patients who did not live long enough to undergo NGS testing were not included. Results seen in the veteran population served by the Veterans Health Administration may not be generalizable to the broader population.

DISCLOSURES: The study received support from Challenge Award PCF22CHALO2 from the Prostate Cancer Foundation and the Veterans Affairs National Precision Oncology Program. Luca F. Valle, MD, reported receiving grant support from the Bristol Myers Squibb Foundation during the conduct of the study. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE: Next-generation sequencing (NGS) analysis of 5015 veterans with metastatic prostate cancer reveals distinct genomic patterns between non-Hispanic Black and White patients, with Black veterans showing higher odds of immunotherapy targets but lower odds of androgen receptor axis alterations. However, the rates of survival were similar despite the differences.

METHODOLOGY: 
Researchers conducted a retrospective cohort study comparing alteration frequencies between 1784 non-Hispanic Black (35.6%) and 3,231 non-Hispanic White (64.4%) veterans who underwent NGS testing from January 23, 2019, to November 2, 2023.

•      Analysis included DNA sequencing data from tissue or plasma biospecimens, including prostate biopsy specimens, radical prostatectomy specimens, and prostate cancer metastases, all sequenced with FoundationOne CDx or FoundationOne Liquid CDx platforms.
•      Investigators examined pathogenic alterations in individual genes, actionable targets, and canonical prostate cancer pathways, while adjusting for NGS analyte and clinicopathologic covariates.
•      Researchers evaluated associations between alteration frequency and race as well as survival through Cox proportional hazards modeling, stratified by race and adjusted for clinical factors.

TAKEAWAY:
Non-Hispanic Black race and ethnicity was associated with higher odds of genomic alterations in SPOP (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.2-2.6) and immunotherapy targets (OR, 1.7; 95% CI, 1.1-2.5), including high microsatellite instability status (OR, 3.1; 95% CI, 1.1-9.4).

•      Non-Hispanic Black veterans showed lower odds of genomic alterations in the AKT/PI3K pathway (OR, 0.6; 95% CI, 0.4-0.7), androgen receptor axis (OR, 0.7; 95% CI, 0.5-0.9), and tumor suppressor genes (OR, 0.7; 95% CI, 0.5-0.8).
•      Tumor suppressor alterations were associated with shorter overall survival in both non-Hispanic Black (hazard ratio [HR], 1.54; 95% CI, 1.13-2.11) and non-Hispanic White (HR, 1.52; 95% CI, 1.25-1.85) veterans.
•      CDK12 alterations significantly increased the hazard of death in non-Hispanic Black veterans (HR, 2.04; 95% CI, 1.13-3.67), while immunotherapy targets were associated with increased mortality in non-Hispanic White veterans (HR, 1.44; 95% CI, 1.02-2.02).

IN PRACTICE: " we did not identify any genomic alterations or biomarkers that should not be tested in PCa based on patient self-identified race. Ultimately, this work emphasizes that precision oncology enables the individualization of treatment decisions without having to rely on imprecise characteristics such as self-identified race.," wrote the study authors.

SOURCE: Isla P. Garraway, MD, PhD; Kosj Yamoah, MD, PhD; and Kara N. Maxwell, MD, PhD were co-senior authors. The article was published online on May 12 in JAMA Network Open.

LIMITATIONS: According to the authors, a lack of matched germline data for patients, complicated the interpretation of plasma results. In addition, survivorship bias may have inadvertently excluded the most aggressive metastatic prostate cancer phenotypes, as patients who did not live long enough to undergo NGS testing were not included. Results seen in the veteran population served by the Veterans Health Administration may not be generalizable to the broader population.

DISCLOSURES: The study received support from Challenge Award PCF22CHALO2 from the Prostate Cancer Foundation and the Veterans Affairs National Precision Oncology Program. Luca F. Valle, MD, reported receiving grant support from the Bristol Myers Squibb Foundation during the conduct of the study. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.