The Germline HSD3B1 Variant Is Associated With Response to Androgen Deprivation Therapy and Abiraterone but not With Response to Enzalutamide in Chinese Prostate Cancer Patients.

[BACKGROUND] To investigate the role of HSD3B1 germline variant (1245C) in hormone therapy outcomes in Chinese prostate cancer (PCa) patients.

[METHODS] A multi-center observational study was conducted enrolling 785 PCa patients who received primary androgen deprivation therapy (ADT) in China. Genotyping of germline variant and survival data were obtained, and clinical outcomes were analysed using Cox regression models.

[RESULTS] The median follow-up time was 31 months. In the entire study cohort, the HSD3B1 variant (1245C) was significantly associated with a shorter time to castration resistance after adjusting for Gleason grade group (dominant model: hazard ratio, HR = 1.62, 95% confidence interval, 95% CI: 1.10-2.40, p = 0.015; additive model: HR = 1.55, 95% CI: 1.12-2.13, p = 0.008). Subgroup analysis (n = 438) with patients receiving only ADT for HSPC revealed a more significant association between the C allele and ADT failure (dominant model: HR = 2.37, 95% CI: 1.49-3.77, p < 0.001; additive model: HR = 1.93, 95% CI: 1.34-2.79, p < 0.001). Among patients who received next-generation hormone therapy after ADT failure, the C allele was associated with poorer abiraterone response (HR = 3.02, 95% CI: 1.07-8.50, p = 0.037); however, no significant change of response from enzalutamide was observed (HR = 0.98, 95% CI: 0.27-3.51, p = 0.972).

[CONCLUSIONS] The HSD3B1 germline variant (1245C) is linked to earlier ADT failure and diminished efficacy of abiraterone but does not affect enzalutamide in the treatment of PCa patients. These findings underscore its potential as a biomarker to guide personalized treatment in PCa.