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
| Autor: | Paige L. Dorn, Carlos A. Martinez, Daniel W. Golden, Fauzia Arif, Benjamin E. Onderdonk, Tatjana Antic, Stanley L. Liauw, Denise Cloutier, Russell Z. Szmulewitz, Theodore Karrison, Sean P. Pitroda |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Oncology Cancer Research medicine.medical_specialty Antineoplastic Agents Hormonal Bicalutamide medicine.medical_treatment Comorbidity Androgen deprivation therapy 03 medical and health sciences Prostate cancer chemistry.chemical_compound 0302 clinical medicine Prostate Internal medicine medicine Humans Prospective Studies 030212 general & internal medicine Aged business.industry Prostatic Neoplasms Androgen Antagonists medicine.disease Androgen receptor Radiation therapy medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Quality of Life Finasteride Feasibility Studies Hormonal therapy Transcriptome business medicine.drug |
| Zdroj: | Cancer. 127:2631-2640 |
| ISSN: | 1097-0142 0008-543X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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