658P - Impact of a mutation in HSD3B1 gene on the effectiveness of androgenic deprivation treatment in prostate cancer

Background

Patients with advanced prostate cancer who receive androgen deprivation therapy (ADT) develop castration-resistant disease during the treatment. HSD3B1 gen encodes the enzyme related with resistant mechanism to ADT. Several studies have shown that the presence of rs1047303 polymorphism in HSD3B1 gen (1245 A>C allele) behaves as a predictive biomarker of shortened ADT response.

Methods

Prospective and multicenter study was carried out during 29 months (October 2017- February 2020). Adults patients with castration-resistant prostate cancer (CRPC) on ADT treatment were included: ECOG < 3, adequate hepatic and hematopoietic function. The effectiveness was evaluated depending on progression free survival (PFS) considering biochemical, symptomatic and/or radiological progression. Germline DNA (gDNA) was isolated from a drop of dried blood deposited on a Whatman^TM 903 card paper according to the protocol of Ramos et al. (2015). Characterization of the HSD3B1 gene was performing by real time PCR using specific hybridization probes for the 1245A (wild type) and 1245C (mutant) alleles in the Light Cycler® 480 platform. The statistical analysis was carried out by Breslow adjustment obtaining Kaplan-Meier curves using SPSS® version 22.2 statistical program. The patients signed an informed consent for their participation in the study.

Results

During the study 68 patients with castration-resistant prostate cancer were included with an average age of 63 years old (48-89). HSD3B1 genotyping determined that 1245C allele was presented in 31 heterozygous patients (A/C) and in 7 homozygous mutant patients (C/C). The remaining 30 patients were wild type (A/A). Homozygous mutant patients had a significantly lower median PFS than heterozygous and wild type patients (18.0 vs. 54.0; Log-Rank test; p= 0.01). The presence of only one mutant allele is not associated with a worse PFS (54.0 vs 44.0 months; Log-Rank test; p=0.376).

Conclusions

In our study population, rs1047303 polymorphism in HSD3B1 gene (1245 A>C allele) has behaved as a negative marker for ADT. This screening of CRPC patients could be used to identify patients with rapid progression to ADT and to follow them more closely.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Martín-Abreu CM.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.