[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 34.204.52.4. Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Brief Report
April 2018

Association of HSD3B1 Genotype With Response to Androgen-Deprivation Therapy for Biochemical Recurrence After Radiotherapy for Localized Prostate Cancer

Author Affiliations
  • 1Department of Radiation Oncology, University of Michigan, Ann Arbor
  • 2Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
  • 3Department of Urology, Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, Ohio
  • 4Department of Medicine, Memorial Sloan Kettering Cancer Center New York, New York
  • 5Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
  • 6Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
JAMA Oncol. 2018;4(4):558-562. doi:10.1001/jamaoncol.2017.3164
Key Points

Question  Does inheritance of the variant HSD3B1 (1245C) allele predict worse clinical outcomes in men treated with androgen-deprivation therapy (ADT) for biochemically recurrent prostate cancer after primary radiotherapy?

Findings  In this cohort of 213 men treated at a large academic center and retrospectively genotyped, inheritance of the HSD3B1 (1245C) allele was not associated with a shorter time to progression or overall survival, but it was associated with shorter times to metastasis according to the number of variant alleles inherited.

Meaning  The variant HSD3B1 (1245C) allele was associated with more rapid development of metastases in men receiving ADT for biochemical recurrence after primary radiotherapy.

Abstract

Importance  The variant HSD3B1 (1245C) allele enhances dihydrotestosterone synthesis and predicts resistance to androgen-deprivation therapy (ADT) for biochemically recurrent prostate cancer after prostatectomy and for metastatic disease. Whether this is true after radiotherapy is unknown.

Objective  To determine whether the HSD3B1 (1245C) allele predicts worse clinical outcomes from ADT for biochemical recurrence after radiotherapy.

Design, Setting, and Participants  The Prostate Clinical Research Information System at Dana-Farber Cancer Institute was used to identify the study cohort, which included men treated with ADT for biochemical recurrence after primary radiotherapy between 1996 and 2013. We retrospectively determined HSD3B1 genotype.

Main Outcomes and Measures  Time to progression, time to metastasis, and overall survival according to genotype. Demographic and treatment characteristics were evaluated for confounders. Multivariable analyses were performed to adjust for known prognostic factors.

Results  A total of 218 eligible men were identified, of whom 213 (98%) were successfully genotyped. Of these, 97 of 213 (46%), 96 of 213 (45%) and 20 of 213 (9%) carried 0, 1, and 2 variant alleles. Overall variant allele frequency was 136 of 426 alleles (32%). Median patient age (interquartile range) was 69 (63-74), 72 (65-78), and 69 (65-77) years for 0, 1, and 2 variant alleles (P = .03). Demographic and treatment factors were otherwise similar. During a median follow-up of 7.9 years, median time to progression was 2.3 years (95% CI, 1.6-3.1 years) with 0 variant alleles, 2.3 years (95% CI, 1.5-3.3 years) with 1 variant allele, and 1.4 years (95% CI, 0.7-3.3 years) with 2 variant alleles (P = .68). Median time to metastasis diminished with the number of variant alleles inherited: 7.4 (95% CI, 6.7-9.7), 5.8 (95% CI, 4.9-6.5), and 4.4 (95% CI, 3.0-5.7) years, with inheritance of 0, 1, and 2 variant alleles, respectively (P = .03). Median OS was 7.7 (95% CI, 6.7-10.3), 6.9 (95% CI, 5.8-8.4), and 7.2 (95% CI, 3.8-7.9) years with inheritance of 0, 1, and 2 variant alleles, respectively (P = .31). On multivariable analysis with 0 variant alleles as the reference, the adjusted hazard ratio for metastasis was 1.19 (95% CI, 0.74-1.92) (P = .48) for 1 variant allele and 2.01 (95% CI, 1.02-3.97) (P = .045) for 2 variant alleles. Multivariable analysis did not demonstrate significant differences in TTP or OS.

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

×