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.

Abstract

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.

• Authors: Benjamin E Onderdonk, Paige L Dorn, Carlos Martinez, Fauzia Arif, Denise Cloutier, Tatjana Antic, Daniel W Golden, Theodore Karrison, Sean P Pitroda, Russell Z Szmulewitz, Stanley L Liauw
• Journal: Cancer (Cancer) Vol. 127 Issue 15 Pg. 2631-2640 (08 01 2021) ISSN: 1097-0142 [Electronic] United States
• PMID: 33882144 (Publication Type: Journal Article)
• Copyright: © 2021 American Cancer Society.

Chemical References

• Androgen Antagonists
• Antineoplastic Agents, Hormonal

Topics

• Aged
• Androgen Antagonists (adverse effects)
• Antineoplastic Agents, Hormonal
• Comorbidity
• Feasibility Studies
• Humans
• Male
• Prospective Studies
• Prostatic Neoplasms (drug therapy, genetics, radiotherapy)
• Quality of Life
• Transcriptome