A prospective clinical and transcriptomic feasibility study of oral-only hormonal therapy with radiation for unfavorable prostate cancer in men 70 years of age and older or with comorbidity.
5-α-reductase inhibitor (5-ARI)
comorbidity
dutasteride
finasteride
luteinizing hormone-releasing hormone
prostate cancer
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
01 08 2021
01 08 2021
Historique:
revised:
05
02
2021
received:
11
12
2020
accepted:
04
03
2021
pubmed:
22
4
2021
medline:
8
3
2022
entrez:
21
4
2021
Statut:
ppublish
Résumé
Androgen deprivation therapy (ADT) improves outcomes in unfavorable-risk prostate cancer (PCa) treated with radiation therapy (RT). It was hypothesized that replacing luteinizing hormone-releasing hormone (LHRH) agonists with a 5-α-reductase inhibitor (5-ARI) would improve hormonal health-related quality of life (HRQOL) without differentially suppressing androgen-responsive (AR) gene expression. Patients with localized unfavorable-risk PCa, aged ≥70 years or Charlson Comorbidity Index score ≥2 were treated with oral ADT (oADT), consisting of 4 months of bicalutamide, a 5-ARI, and RT at 78 Gy. The primary end point was Expanded Prostate Cancer Index Composite HRQOL at 6 months ≤30%, and improvement compared with a synchronous standard of care (SOC) cohort receiving 4 months of bicalutamide and long-term LHRH agonist with RT. RNA sequencing was performed from matched pre-/post-ADT prostate tumor biopsies in a subset of men. Differential gene and pathway expressional changes were examined using gene set enrichment. Between 2011 and 2018, 40 and 30 men were enrolled in the oADT and SOC cohorts, respectively. Median follow-up was 40 months. Those with ≤30% decline in hormonal HRQOL at 6 months was 97% (oADT) and 93% (SOC). The average 6-month hormonal decline was 1% (oADT) versus 12% (SOC; P = .04). The 4-year freedom from biochemical failure was 88% (oADT) versus 81% (SOC; P = .48). RNA sequencing (n = 9) showed similar numbers of downregulated and upregulated genes between the treatment groups (fold-change = 2; false-discovery rate-adjusted P ≤ .05). Both treatments comparably decreased the expression of 20 genes in canonical androgen receptor signaling. For men with PCa undergoing RT, oral versus standard ADT may improve 6-month QOL and appears to have a similar impact on androgen-responsive gene expression.
Sections du résumé
BACKGROUND
Androgen deprivation therapy (ADT) improves outcomes in unfavorable-risk prostate cancer (PCa) treated with radiation therapy (RT). It was hypothesized that replacing luteinizing hormone-releasing hormone (LHRH) agonists with a 5-α-reductase inhibitor (5-ARI) would improve hormonal health-related quality of life (HRQOL) without differentially suppressing androgen-responsive (AR) gene expression.
METHODS
Patients with localized unfavorable-risk PCa, aged ≥70 years or Charlson Comorbidity Index score ≥2 were treated with oral ADT (oADT), consisting of 4 months of bicalutamide, a 5-ARI, and RT at 78 Gy. The primary end point was Expanded Prostate Cancer Index Composite HRQOL at 6 months ≤30%, and improvement compared with a synchronous standard of care (SOC) cohort receiving 4 months of bicalutamide and long-term LHRH agonist with RT. RNA sequencing was performed from matched pre-/post-ADT prostate tumor biopsies in a subset of men. Differential gene and pathway expressional changes were examined using gene set enrichment.
RESULTS
Between 2011 and 2018, 40 and 30 men were enrolled in the oADT and SOC cohorts, respectively. Median follow-up was 40 months. Those with ≤30% decline in hormonal HRQOL at 6 months was 97% (oADT) and 93% (SOC). The average 6-month hormonal decline was 1% (oADT) versus 12% (SOC; P = .04). The 4-year freedom from biochemical failure was 88% (oADT) versus 81% (SOC; P = .48). RNA sequencing (n = 9) showed similar numbers of downregulated and upregulated genes between the treatment groups (fold-change = 2; false-discovery rate-adjusted P ≤ .05). Both treatments comparably decreased the expression of 20 genes in canonical androgen receptor signaling.
CONCLUSIONS
For men with PCa undergoing RT, oral versus standard ADT may improve 6-month QOL and appears to have a similar impact on androgen-responsive gene expression.
Substances chimiques
Androgen Antagonists
0
Antineoplastic Agents, Hormonal
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2631-2640Informations de copyright
© 2021 American Cancer Society.
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