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Association of HSD3B1 genotype with response to androgen-deprivation therapy for biochemical recurrence after radiotherapy for localized prostate cancer

JAMA Oncology Oct 26, 2017

Hearn JWD, et al. - This trial investigated the possibility that the HSD3B1 (1245C) allele speculated worse clinical outcomes from androgen-deprivation therapy (ADT) for biochemical recurrence after radiotherapy. The results shed light on the correlation between the HSD3B1 (1245C) allele with a more rapid development of metastases in men treated with ADT for biochemical recurrence, after primary radiation therapy for prostate cancer. It was reported that 105 of 213 men (49%) had received prior ADT, and 119 of 213 (56%) received an androgen receptor antagonist during salvage treatment. Both could attenuate the effect of the variant allele.

Methods

  • For the purpose of enrollment, this study utilized the Prostate Clinical Research Information System at Dana-Farber Cancer Institute.
  • The eligible candidates were men treated with ADT for biochemical recurrence after primary radiotherapy between 1996 and 2013.
  • A retrospective determination was pursued of the HSD3B1 genotype.
  • The main outcome measure comprised of the time to progression, time to metastasis, and overall survival according to genotype.
  • Analysis was conducted of the demographic and treatment characteristics for confounders.
  • Multivariable analyses aided in adjusting for known prognostic factors.

Results

  • 218 men were enrolled, of whom 213 (98%) were successfully genotyped.
  • 97 patients of 213 (46%), 96 of 213 (45%) and 20 of 213 (9%) carried 0, 1, and 2 variant alleles.
  • It was reported that the 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).
  • Similar demographic and treatment factors were found.
  • The 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), during a median follow-up of 7.9 years.
  • It was disclosed that the 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).
  • 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, on multivariable analysis with 0 variant alleles as the reference.
  • No prominent variations were illustrated by the multivariable analysis, in TTP or OS.

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