Real-world analysis of targeted tumor genomic profiles in prostate cancer among Black and White men within the MedStar Health Network.

Abstract

e22523 Background: Prostate cancer (PC) outcome disparities between White and Black men result from a combination of biologic and socioeconomic factors. Utilizing next-generation sequencing (NGS) is key to precision oncology. This study explores the association between targeted tumor genomic profiles, disease biology, and social determinants of health. Methods: This is a real-world prospective cohort study of men diagnosed with advanced PC who received standard of care (SOC) between 2023 to 2025. NGS was performed on tissue biopsy samples at Caris Life Sciences as part of SOC. Data on disease biology at diagnosis (stage, Gleason score, PSA), NGS prior to first-line systemic therapy, and national area deprivation index (ADI) by quartile was analyzed using Chi-square test. Results: A cohort of 87 men (52.8% Black, 43.6% White, 3.4% Other) were included. Eleven men did not have molecular data available. The association between Gleason score (low/intermediate [6-7] vs. high [8-10]), stage (I-II, III, IV), and PSA (low, intermediate, high) compared to national ADI quartile (Q1-Q4) was not statistically significant (p = 0.16, 0.92, 0.58). Clinically, Black patients presented with significantly higher PSA levels at diagnosis (p = 0.04), but there was no significant association between stage and race (p = 0.97). Fifteen targeted mutations were seen in DNA damage repair genes (DDR) and oncogenic signaling with seven appearing in black and five in white males. All targeted mutations were observed in patients with high Gleason scores. Pairwise chi-square analysis found no significant difference between race and ADI quartile versus targeted mutation status (p = 0.98, p = 0.66), however a statistically significant difference was observed between PSA and targeted mutation status (p = 0.004). Sixty-one mutations were found in tumor suppressor genes (52.5% White and 47.5% Black). Fifty-two mutations were found in androgen receptor and prostate lineage genes (48.1% White and 48.1% Black). Forty-two mutations were found in DDR genes (26.2% White and 73.8% Black). Twenty-four mutations were found in oncogenic signaling genes (37.5% White and 62.5% Black). Twenty-one mutations were seen in epigenetic/transcriptional genes (38.1% White and 57.1% Black). Conclusions: This study combines early genomic profiling with disease biology to inform risk-reductive treatment strategies. Our study uniquely utilizes a racially balanced prospective cohort; however, the limited sample size limited our scope to a descriptive analysis. Targetable genomics were observed in higher Gleason scores and diverse mutations profiles including DDR, oncogenic signaling, and transcriptional mutations had higher frequency in Black patients. Identifying population-specific genomic differences, including high-risk alterations, may reveal therapeutic opportunities to reduce clinical outcome disparities.