Stitz Regina, Stoiber Franz, Silye Renè, Rebhan Elisabeth, Dunzinger Michael, Pühringer Franz, Heitzer Ellen, Hauser-Kronberger Cornelia
Department of Pathology, Salzkammergutklinikum Vöcklabruck, Vöcklabruck, Austria.
Doctoral Program Medical Science, Paracelsus Medical University Salzburg, Salzburg, Austria.
Int J Cancer. 2025 Nov 15;157(10):2124-2134. doi: 10.1002/ijc.70019. Epub 2025 Jun 25.
Androgen receptor (AR) alterations contribute to resistance against androgen receptor signaling inhibitors (ARSi) in metastatic castration-resistant prostate cancer (mCRPC). This study evaluated AR alteration monitoring via liquid biopsy in routine clinical practice. To this end, we enrolled 39 mCRPC patients in a real-world clinical setting and monitored disease progression with progression-free survival (PFS) and overall survival (OS) analyzed in relation to AR status. AR alterations were detected in 8 of 39 patients (20.5%) at baseline, with five additional cases emerging during progression (total 33.3%). AR-V7 was identified in 12.8%, and AR amplification and/or hotspot mutations in 20.5%. Patients with AR alterations had significantly lower PSA response rates to ARSi (37.5% vs. 80.7%; p = 0.0276). All AR alteration-positive patients experienced disease progression, compared to 34.6% of AR-negative cases. PFS was significantly shorter in AR alteration-positive patients (11 vs. 52 months; p = 0.001), while OS showed a non-significant trend toward shorter survival (41 vs. 74 months; p = 0.0619). Univariate analysis confirmed AR alterations as an independent predictor of PFS (p = 0.0035). This real-world study demonstrates that AR monitoring via liquid biopsy predicts treatment response and progression in mCRPC. Continuous monitoring is essential, as AR alterations emerge over time. Patients with AR alterations have poorer ARSi responses and shorter PFS, emphasizing the need for adaptive treatment strategies in real-world clinical practice.
雄激素受体（AR）改变导致转移性去势抵抗性前列腺癌（mCRPC）对雄激素受体信号抑制剂（ARSi）产生耐药性。本研究评估了在常规临床实践中通过液体活检监测AR改变的情况。为此，我们纳入了39例处于真实临床环境中的mCRPC患者，并通过无进展生存期（PFS）和总生存期（OS）监测疾病进展，并分析其与AR状态的关系。在基线时，39例患者中有8例（20.5%）检测到AR改变，在疾病进展过程中又出现了另外5例（总计33.3%）。AR-V7在12.8%的患者中被鉴定出来，AR扩增和/或热点突变在20.5%的患者中被检测到。发生AR改变的患者对ARSi的PSA反应率显著较低（37.5%对80.7%；p = 0.0276）。与34.6%的AR阴性病例相比，所有AR改变阳性的患者均经历了疾病进展。AR改变阳性患者的PFS显著缩短（11个月对52个月；p = 0.001），而OS显示出生存期缩短的非显著趋势（41个月对74个月；p = 0.0619）。单因素分析证实AR改变是PFS的独立预测因素（p = 0.0035）。这项真实世界研究表明，通过液体活检监测AR可预测mCRPC的治疗反应和疾病进展。由于AR改变会随时间出现，持续监测至关重要。发生AR改变的患者对ARSi的反应较差且PFS较短，这强调了在真实世界临床实践中采用适应性治疗策略的必要性。
