ASCO GU 2021: Genomic Landscape of Advanced Prostate Cancer in Racial Minority Populations

(UroToday.com) The largest United States cancer health disparity exists in prostate cancer, with African American men having: 

• ~1.6-1.8-fold higher risk of developing prostate cancer
• Younger age and more advanced stage at diagnosis
• Increased risk of recurrence after radical prostatectomy
• Up to 2.5-fold higher mortality rate relative to men of other ancestries

Access to healthcare and other socioeconomic and environmental factors contribute to the disparity in clinical outcomes. However, genetic factors may also be involved, and their role and prevalence need to be better defined, especially in real-world clinical settings, as the high cost of next-generation sequencing may have resulted in underrepresentation of uninsured and minority patients in prior studies. At the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), Dr. Tamer Khashab presented results of their real-world experience assessing the genomic landscape of advanced prostate cancer in racial minority populations.

The Ben Taub Hospital is located in Harris County, Houston, Texas and is a community focused academic healthcare system, focused on need-based care and education. Cancer patients in the Harris Health care system are made up of 50.7% Hispanic patients and 27.8% African American patients. Specific to prostate cancer patients at Ben Taub Hospital, 55% are African American and 35% are Hispanic. 

This study retrospectively analyzed next-generation sequencing data obtained via Tempus|xT tissue assay (DNA sequencing of 648 genes in tumor and matched normal samples at 500x depth) and/or Tempus|xF liquid biopsy assay (ctDNA sequencing of 105 genes in peripheral blood samples at 5,000x depth) for germline and/or somatic mutations detected in 100 patients (53 African American) receiving androgen deprivation therapy for locally advanced, biochemically recurrent or metastatic prostate cancer at Ben Taub Hospital. For confirmation, Dr. Khashab and colleagues analyzed de-identified next-generation sequencing data from a nationwide cohort of 1,211 metastatic prostate cancer patients (213 African Americans) previously sequenced with xT and/or xF by Tempus Labs (Chicago, IL).

African American prostate cancer patients with advanced disease have a higher incidence of gene alterations in several cancer drivers. This included higher frequencies of AR (18.9%), TP53 (41.5%), SPOP (20.7%) and homologous recombination repair (HRR) pathway gene mutations (22.6%), in particular BRCA2 (17%), as compared to prostate cancer patients of other races/ethnicities:

This was confirmed in the nationwide Tempus Labs cohort, with 44.0% of African American patients exhibiting mutation in at least one of 14 homologous recombination repair pathway genes associated with prostate cancer sensitivity to PARP inhibitors, compared to 34.6% in non-African American patients (p < 0.05): 

This difference was mainly driven by higher frequency of BRCA2 (16.9%), CDK12 (8%) and PALB2 (5.2%) mutations in African American patients. In both cohorts, TMPRSS2 fusions were much less common in African American prostate cancer patients.

Dr. Khashab concluded his presentation with the following summary remarks:

• This study provides a real-world snapshot of the genomic landscape of advanced prostate cancer patients from a hospital serving a large population of racial/ethnic minorities, including African American men, as well as from a nationwide prostate cancer cohort
• The observed high frequency of mutations in key prostate cancer drivers in African American patients may reflect differences in disease biology between racial/ethnic groups or the more advanced disease presentation of African American patients due to socioeconomic factors delaying access to healthcare
• Next-generation sequencing of tumor tissue or liquid biopsies can uncover additional targeted therapy options for prostate cancer minority patients, including on- or off-label FDA approved therapies and biomarker-based Precision Oncology clinical trials

Presented by: Tamer Khashab, MD, Harris Health/Ben Taub Hospital, Houston, TX