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<p>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, <i>AR</i> RNA splice variants (ARVs), including ligand-independent <i>AR-V7</i>, 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 <i>AR</i> transcript pool from prostatectomy specimens from 43 men who later received salvage RT+ADT. Eighty-six percent of patients had detectable <i>ARVs</i> (median 3, range 0-12). Of the thirty-two unique <i>ARVs</i> detected, only <i>AR-V7</i> (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 <i>AR-V7</i> may modulate outcomes for localized in addition to metastatic prostate cancer.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月1日

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  • David J. Konieczkowski,
  • Keisuke Otani,
  • Zoe Guan,
  • Michael R. Drumm,
  • Yukako Otani,
  • Priscilla Oluwakemi Badusi,
  • Ella H. Chung,
  • Shulin Wu,
  • Elai Davicioni,
  • Philip J. Saylor,
  • Chin-Lee Wu,
  • Jason A. Efstathiou,
  • David T. Miyamoto

摘要

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.