Castration-resistant prostate cancer (CRPC) “treatment emergent” types, such as aggressive variant prostate cancer (AVPC), are recognized by elevated blood carcinoembryonic antigen (CEA). However, neither its individual prognostic value nor the genetic changes linked to its expression have been thoroughly investigated in CRPC.

In 163 patients with CRPC and high or normal blood CEA, the researchers retrospectively examined the clinical outcomes and circulating tumor DNA profiles for a study. To ascertain the distinctiveness of CEA-associated gene changes, the same individuals were subsequently divided into AVPC and non-AVPC groups and compared.

Higher rates of liver metastasis were seen in patients with increased CEA (37.5% vs. 19.1%, P=0.02) and shorter median overall survival following CRPC diagnosis (28.7 vs. 73.2 mo, P<0.0001). The presence of copy number amplifications (CNAs) in the genes AR, PIK3CA, MYC, BRAF, CDK6, MET, CCNE1, KIT, RAF1, and KRAS was also more prevalent in patients with increased CEA. They identified “clonal” single-nucleotide variants (SNVs) based on variant allele frequency and found that CEA expression was negatively connected with clonal AR SNVs and favorably correlated with clonal TP53 SNVs. Only the increases in clonal TP53 SNVs and KRAS amplifications were replicated among patients with AVPC compared to patients without AVPC among these genetic relationships.

All of the results pointed to the possibility that aggressive clinical behavior and gene changes separate from those seen in AVPC are linked to CEA expression in CRPC.