Transcriptomic Signatures Associated With Outcomes in Recurrent Prostate Cancer Treated With Salvage Radiation, Androgen-Deprivation Therapy, and Enzalutamide : Correlative Analysis of the STREAM Trial
PURPOSE: Men with rising prostate-specific antigen (PSA) after radical prostatectomy (RP) may progress despite radiation and androgen-deprivation therapy (ADT). Tissue-based transcriptomic signatures can identify who may benefit from a more aggressive systemic approach.
METHODS: We performed a retrospective analysis of a prospective phase II multicenter trial of enzalutamide, ADT, and salvage radiotherapy in men with rising PSA after RP. Tumor tissue was analyzed using the Decipher platform for gene expression, including a novel prostate subtyping classifier, PTEN loss, homologous recombination deficiency (HRD), and ADT response. Cox models were used to associate signature scores with progression-free survival (PFS).
RESULTS: Of the 38 men enrolled, 31 had tissue with sufficient-quality RNA for genomic analysis. Luminal differentiated (LD) subtype tumors had the longest 3-year PFS at 89% compared with 19% in the luminal proliferating subtype. Men with signatures of PTEN loss (hazard ratio [HR], 1.32; 95% CI, 1.07 to 1.64; P = .01) or HRD (HR, 1.21; 95% CI, 1.05 to 1.39; P = .009) had worse PFS, while those with higher ADT response signature scores (HR, 0.75; 95% CI, 0.61 to 0.94; P = .01) were associated with improved PFS. Analysis of these signatures in a large cohort (n = 5,330) of RP samples from patients with biochemical recurrence found that these signatures provide complementary information related to outcomes with salvage radiation.
CONCLUSION: Despite aggressive systemic therapy with salvage radiation, nearly 50% of high-risk men relapse within 3 years. We show that LD and higher ADT sensitivity tumors had favorable outcomes. Those with a luminal proliferating subtype, PTEN loss, and/or HRD signatures had poor outcomes despite ADT/radiation and enzalutamide and may benefit from alternative approaches.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
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| Enthalten in: |
JCO precision oncology - 7(2023) vom: 03. Aug., Seite e2300214 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bitting, Rhonda L [VerfasserIn] |
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| Links: |
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| Themen: |
93T0T9GKNU |
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| Anmerkungen: |
Date Completed 21.08.2023 Date Revised 10.02.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1200/PO.23.00214 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM360939821 |
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| 100 | 1 | |a Bitting, Rhonda L |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Transcriptomic Signatures Associated With Outcomes in Recurrent Prostate Cancer Treated With Salvage Radiation, Androgen-Deprivation Therapy, and Enzalutamide |b Correlative Analysis of the STREAM Trial |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 21.08.2023 | ||
| 500 | |a Date Revised 10.02.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a PURPOSE: Men with rising prostate-specific antigen (PSA) after radical prostatectomy (RP) may progress despite radiation and androgen-deprivation therapy (ADT). Tissue-based transcriptomic signatures can identify who may benefit from a more aggressive systemic approach | ||
| 520 | |a METHODS: We performed a retrospective analysis of a prospective phase II multicenter trial of enzalutamide, ADT, and salvage radiotherapy in men with rising PSA after RP. Tumor tissue was analyzed using the Decipher platform for gene expression, including a novel prostate subtyping classifier, PTEN loss, homologous recombination deficiency (HRD), and ADT response. Cox models were used to associate signature scores with progression-free survival (PFS) | ||
| 520 | |a RESULTS: Of the 38 men enrolled, 31 had tissue with sufficient-quality RNA for genomic analysis. Luminal differentiated (LD) subtype tumors had the longest 3-year PFS at 89% compared with 19% in the luminal proliferating subtype. Men with signatures of PTEN loss (hazard ratio [HR], 1.32; 95% CI, 1.07 to 1.64; P = .01) or HRD (HR, 1.21; 95% CI, 1.05 to 1.39; P = .009) had worse PFS, while those with higher ADT response signature scores (HR, 0.75; 95% CI, 0.61 to 0.94; P = .01) were associated with improved PFS. Analysis of these signatures in a large cohort (n = 5,330) of RP samples from patients with biochemical recurrence found that these signatures provide complementary information related to outcomes with salvage radiation | ||
| 520 | |a CONCLUSION: Despite aggressive systemic therapy with salvage radiation, nearly 50% of high-risk men relapse within 3 years. We show that LD and higher ADT sensitivity tumors had favorable outcomes. Those with a luminal proliferating subtype, PTEN loss, and/or HRD signatures had poor outcomes despite ADT/radiation and enzalutamide and may benefit from alternative approaches | ||
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Wu, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Somarelli, Jason A |e verfasserin |4 aut | |
| 700 | 1 | |a Proudfoot, James A |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Davicioni, Elai |e verfasserin |4 aut | |
| 700 | 1 | |a George, Daniel J |e verfasserin |4 aut | |
| 700 | 1 | |a Armstrong, Andrew J |e verfasserin |4 aut | |
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