(UroToday.com) The 2025 ASCO annual meeting featured a prostate cancer session and a presentation by Dr. Sharon Choi discussing comprehensive genomic profiling of Black and non-Hispanic White men with prostate cancer. Racial disparities are evident in prostate cancer, with Black men experiencing a higher incidence and worse survival compared to non-Hispanic White patients. However, the molecular alterations that distinguish these groups remain incompletely characterized. At the ASCO 2025 annual meeting, Dr. Choi and colleagues investigated the clinical-genomic features that potentially contribute to the differences in outcomes between Black and non-Hispanic White patients with prostate cancer.
Comprehensive next-generation sequencing of DNA (592-gene panel/whole exome) and RNA (whole transcriptome) was performed on prostate cancer tissue samples (n = 5,412), collected from 2015 to 2023. Transcriptomic signatures – androgen receptor, neuroendocrine prostate cancer scores – were calculated. Castration sensitive prostate cancer was defined as a specimen collected <90 days after ADT initiation, and castration resistant cancer was defined as a specimen collected >90 days after ADT initiation. Real-world overall survival data were obtained from insurance claims and were analyzed using Kaplan-Meier estimation.
Overall, 1,078 patients with prostate cancer identified as Black, while 4,334 were non-Hispanic White. Black patients were younger at biopsy collection than non-Hispanic White patients (median age 66 versus 71 years, p < 0.001). The proportion of metastatic samples was higher in Black patients compared to non-Hispanic White patients (43% versus 38%, p < 0.01), however, the prevalence of castrated prostate cancer specimens was similar between Black and non-Hispanic White patients (34% versus 33%, p = 0.504):
Among non-castrated prostate cancer tumors, tumors from non-Hispanic White patients had more frequent alterations in TP53, PTEN, PIK3CA, and CHEK2, while tumors from Black patients had more SPOP and CTNNB1 mutations. In the castrate setting, TP53 and PTEN alterations were more frequent in tissue samples from non-Hispanic White patients, while CDK12 and SPOP mutations were more frequent in tumors from Black patients. TMPRSS2 fusions were more prevalent in the non-Hispanic White cohort across both castrated and non-castrated tumors:
Tumors from Black patients had higher FOLH1/PSMA and STEAP1 expression, elevated androgen receptor scores, but lower CD276/B7H3 expression and neuroendocrine prostate cancer scores:
In the overall cohort, Black patients demonstrated a shorter median overall survival from diagnosis compared to non-Hispanic White patients (86 versus 94 months, p = 0.03):
Black patients had a significantly longer time on treatment with enzalutamide in both the non-castrate (HR 0.82, P= 0.04) and castrate subgroups (HR 0.77, p = 0.03). Among patients with homologous recombination repair (HRR) deficiency-harboring tumors, PARP inhibitors provided a numerically longer survival benefit in Black patients than in non-Hispanic White patients (21 versus 13 months, p = 0.09):
Dr. Choi concluded her presentation discussing comprehensive genomic profiling of Black and non-Hispanic White men with prostate cancer with the following take home points:
- This multi-institutional study reveals distinct molecular profiles between Black and non-Hispanic White patients with prostate cancer
- Despite having molecular features associated with better prognosis, Black men demonstrated worse survival outcomes, pointing to multifaceted determinants of disease outcomes
- Notably, Black patients had improved outcomes on enzalutamide and showed potential benefit from PARP inhibitors in the presence of HRR mutations
- These findings highlight genomic differences in diverse prostate cancer populations and suggest therapeutic opportunities to address outcome disparities
Presented by: Sharon Choi, MD, PhD, University of California, San Diego, San Diego, CA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, Chicago, IL, Fri, May 30 – Tues, Jun 3, 2025.
Related content: Racial Disparities in Prostate Cancer Genomics and PARPi Treatment Outcomes - Sharon Choi & Qian Qin