HSD3B1 Genotype and Outcomes With ADT After Radiotherapy for Localized Prostate Cancer

Key Points

  • In patients receiving androgen-deprivation therapy for localized prostate cancer, the presence of the HSD3B1 (1245C) allele was associated with more rapid progression to metastasis after radiotherapy.
  • No effect of the allele was found for the time to disease progression or overall survival. 

In a study reported in JAMA Oncology, Hearn et al found that the presence of the HSD3B1 (1245C) allele was associated with more rapid development of metastases in patients receiving androgen-deprivation therapy for biochemical recurrence after primary radiation therapy for localized prostate cancer. This variant, which encodes a more stable enzyme required for dihydrotestosterone synthesis from extragonadal precursor steroids, has been shown to predict resistance to androgen-deprivation therapy for biochemical recurrence after prostatectomy and for metastatic disease.

Study Details

The study involved 213 successfully genotyped patients from the Prostate Clinical Research Information System at Dana-Farber Cancer Institute who had received androgen-deprivation therapy for biochemical recurrence after primary radiotherapy between 1996 and 2013.

Outcomes According to Genotype

Of the 213 patients, 97 (46%), 96 (45%), and 20 (9%) carried 0, 1, and 2 variant alleles, respectively. Overall variant allele frequency was 136 of 426 alleles (32%). During median follow-up of 7.9 years, the median time to disease progression was 2.3 years with 0 variant alleles, 2.3 years with 1 variant allele, and 1.4 years with 2 variant alleles (P = .68). The median time to metastasis was 7.4, 5.8, and 4.4 years with inheritance of 0, 1, and 2 variant alleles (P = .03). The median overall survival was 7.7, 6.9, and 7.2 years with inheritance of 0, 1, and 2 variant alleles (P = .31). On multivariate analysis, the adjusted hazard ratio for metastasis was 1.19 (P = .48) for 1 variant allele and 2.01 (P = .045) for 2 variant alleles vs 0 variant alleles; no significant differences in the time to disease progression or overall survival according to the number of variant alleles were observed.

The investigators concluded: “In this study, the HSD3B1 (1245C) allele was associated with more rapid development of metastases in men treated with [androgen-deprivation therapy] for biochemical recurrence after primary radiation therapy for prostate cancer. Notably, 105 of 213 men (49%) had received prior [androgen-deprivation therapy], and 119 of 213 (56%) received an androgen receptor antagonist during salvage treatment, both of which may attenuate the effect of the variant allele.”

This work was supported by grants and awards from the U.S. Department of Defense, Prostate Cancer Foundation, American Cancer Society, National Cancer Institute, and others.

Nima Sharifi, MD, of the Cleveland Clinic, is the corresponding author of the JAMA Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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