Androgen receptor splice variant expression and prostate cancer recurrence after salvage therapy

Prostate cancer is driven by androgen receptor (AR) signaling, and radiotherapy (RT) with or without androgen deprivation therapy (ADT) offers a second opportunity at cure for men with local or biochemical recurrence after prostatectomy. In the metastatic setting, AR RNA splice variants (ARVs), including ligand-independent AR-V7, modulate ADT response and tumor radiosensitivity. Here, we hypothesized that ARVs in primary prostate cancer may likewise modulate response to subsequent salvage RT+ADT. We performed ultra-deep RNA-seq of the AR transcript pool from prostatectomy specimens from 43 men who later received salvage RT+ADT. Eighty-six percent of patients had detectable ARVs (median 3, range 0-12). Of the thirty-two unique ARVs detected, only AR-V7 (present in 14% of patients) was associated with outcomes after salvage RT+ADT (HR for second biochemical failure, 6.2, 95% CI 2.3-16.5, p=0.0003). These results suggest for the first time that AR-V7 may modulate outcomes for localized in addition to metastatic prostate cancer.

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Publication Details

Journal
npj Precision Oncology
Published
2025-12-01
DOI
https://doi.org/10.1038/s41698-025-01201-3
Primary Topic
Prostate Cancer Treatment and Research
Type
article
Field-Weighted Citation Impact
0.00
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article

Androgen receptor splice variant expression and prostate cancer recurrence after salvage therapy

Zoe Guan, David T. Miyamoto, Elai Davicioni, Keisuke Otani et al.
npj Precision Oncology
Prostate Cancer Treatment and Research
article

Androgen receptor splice variant expression and prostate cancer recurrence after salvage therapy

Zoe Guan, David T. Miyamoto, Elai Davicioni, Keisuke Otani, Michael Drumm, David Joseph Konieczkowski, Chin‐Lee Wu, Jason A. Efstathiou, Philip J. Saylor, Yukako Otani, Shulin Wu, Priscilla Oluwakemi Badusi, Ella Chung
article en

Abstract

Prostate cancer is driven by androgen receptor (AR) signaling, and radiotherapy (RT) with or without androgen deprivation therapy (ADT) offers a second opportunity at cure for men with local or biochemical recurrence after prostatectomy. In the metastatic setting, AR RNA splice variants (ARVs), including ligand-independent AR-V7, modulate ADT response and tumor radiosensitivity. Here, we hypothesized that ARVs in primary prostate cancer may likewise modulate response to subsequent salvage RT+ADT. We performed ultra-deep RNA-seq of the AR transcript pool from prostatectomy specimens from 43 men who later received salvage RT+ADT. Eighty-six percent of patients had detectable ARVs (median 3, range 0-12). Of the thirty-two unique ARVs detected, only AR-V7 (present in 14% of patients) was associated with outcomes after salvage RT+ADT (HR for second biochemical failure, 6.2, 95% CI 2.3-16.5, p=0.0003). These results suggest for the first time that AR-V7 may modulate outcomes for localized in addition to metastatic prostate cancer.

npj Precision OncologyVol. 10(1)
Broad Institute (US), Harvard University (US), The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US), Massachusetts General Hospital (US), Veracyte (United States) (US), Global Cancer Institute (US), Center for Cancer Research (US), The Ohio State University (US)
Openalex Percentile: Top 44%
Prostate Cancer Treatment and Research
DOIOpen Access PDFOpenAlex
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