Background : Somatic genetic analyses have indicated genetic distinctions in AA as compared to C patients. In the Mahal et al. study (1) evaluating a broad spectrum of pts with tissue based assays, FOXA1 mutations were more frequent in AA men and TP53 mutations were less frequent in AA men as compared to C men. In a separate analysis by Khashab et al. (2) conducted in prostate cancer pts receiving androgen deprivation therapy, using both tissue and ctDNA assays, the authors reported AR,TP53, SPOP, and BRCA2 were more frequently mutated in AA men as compared to C men. Herein we assessed the Guardant 360 platform in assessing ctDNA differences in AA and C men, all of whom had CRPC at the time assays were performed. Methods: Guardant 360 was used to analyze ctDNA with a cut-off of >0.5% for allelic fractions for ascertaining the presence or absence of pathogenic mutations and various amplifications. Lower allelic fractions were not analyzed given these may represent less relevant mutations. Depending on the timing of the assays (2015-2021), 70-83 genes were analyzed. All pts had CRPC and all patients were treated at Tulane Cancer Center. Chi Square analyses were used to determine statistical differences. AR, BRCA2, and TP53 were assessed but SPOP and FOXA1 were not assessable in the Guardant ctDNA assay. Both mutations and amplifications were evaluated. Results: Among men with CRPC, a total of 48 AA men and 179 C men were analyzed using ctDNA. Clear distinctions were found in the alteration reported in APC, TP53, and CDK12. TP53 was less frequently mutated and other genes were more frequently altered in the AA men. Conclusions: Using Guardant ctDNA assays in men with CRPC, clear distinctions were found in AA men as compared to C men. It is unclear why these results differ from that reported by others, however distinctions in both the assays and the populations are notable.

1. Mahal et al. N Engl J Med 2020; 383:1083-1085 2. Kahshab et al. Journal of Clinical Oncology 39, no. 6_suppl (February 20, 2021) 14.