The impact of HSD3B1 (1245 A>C) polymorphism on clinical outcomes of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone remains under debate. We investigated how HSD3B1 genotypes influence serum levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S), abiraterone, delta-4-abiraterone (D4A) and clinical outcomes of mCRPC patients treated with abiraterone plus prednisone (AAP). Blood samples from 42 mCRPC patients were collected during AAP treatment. HSD3B1 genotypes were determined by Sanger sequencing and analyses were made comparing AA versus AC+CC groups. PSA decline equal or above 50% from baseline (PSA50) at any time, Time to PSA progression (TPP), and Overall Survival (OS) were evaluated. Frequencies of AA, AC and CC HSD3B1 genotypes were 50.0%, 33.3%, and 16.7%, respectively. The HSD3B1 genotype did not influence steroids or drug levels during AAP treatment. PSA50 at any time was 71.4% for AA and 42.9% for the AC+CC group (p=0.061). Median TPP was similar between groups. The AA group had a median OS of 21.3 months, which was not reached by the AC+CC group (p=0.15). PSA50 at any time was lower in the AC+CC compared to AA group, though not statistically significant. The HSD3B1 genotype was not associated with TPP nor with OS.
Bastos et al. (Thu,) studied this question.