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Prostate Cancer Genomics in Racial Minority Groups

Real-world findings
18 Feb 2021
Genitourinary cancers;  Personalised medicine

Dr. Tamer Khashab of the Baylor College of Medicine in Houston, TX, US reported at 2021 Genitourinary Cancers Symposium real-world findings from the advanced prostate cancer genomics analysis performed in a safety net hospital serving large racial/ethnic minority populations. Dr. Khashab and colleagues observed high frequency of mutations in key prostate cancer drivers that may reflect differences in disease biology between racial/ethnic groups or the more advanced disease presentation due to socioeconomic factors delaying access to health care in African American patients. 

The authors explained in the study background that the largest cancer care disparity in US exists in prostate cancer, with African American men having approximately 1.6 to 1.8 fold higher risk of developing prostate cancer, younger age and more advanced stage at diagnosis, increased risk of recurrence after radical prostatectomy and up to 2.5 fold higher mortality rate relative to men of other ancestries. 

Access to health care 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 should be better defined, especially in real-world clinical settings, as the high cost of next-generation sequencing (NGS) may have resulted in underrepresentation of uninsured and minority patients in prior studies. 

They retrospectively analyzed NGS data obtained via Tempus | xT tissue assay (DNA sequencing of 648 genes in tumour 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 from whom 53 were African American and who received androgen deprivation therapy for locally advanced, biochemically recurrent or metastatic prostate cancer at Ben Taub Hospital, a safety net hospital in Harris County/Houston serving a patient population of which 91% are racial/ethnic minorities. 

For confirmation, the study team analyzed deidentified NGS data from the US cohort of 1,211 metastatic prostate cancer patients from whom 213 were African American and previously sequenced with xT and/or xF by Tempus Labs. 

The study investigators found higher frequencies of androgen receptor (18.9%), TP53 (41.5%), SPOP (20.7%) and homologous recombination repair (HRR) pathway gene mutations, in particular BRCA2 (17%), in African American cohort at Ben Taub Hospital, as compared to prostate cancer patients of other races/ethnicities. 

The finding was confirmed in the Tempus Labs cohort of patients across US, with 91 of 213 African American patients (42.7%) exhibiting mutation in at least one of 14 HRR pathway genes associated with prostate cancer sensitivity to PARP inhibitors, compared to 347 of 998 non-African American patients (34.7%) (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. 

The authors concluded that their study provides a real-world experience in terms of the genomic analysis of advanced prostate cancer in the clinical setting serving large racial/ethnic minority populations. 

The study results highlight the role of NGS in improving access of such underserved and underrepresented patient populations to treatment with novel targeted therapies and to biomarker-based clinical studies in precision cancer medicine. 

The study was funded by the US National Institutes of Health.

Reference 

Khashab T, Le AD, Cohen S, et al. Genomic landscape of advanced prostate cancer in racial minority populations: Real-world experience in a safety-net hospital oncology clinic. J Clin Oncol 2021; 39:(suppl 6; abstr 14). DOI: 10.1200/JCO.2021.39.6_suppl.14.

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