Clinical impact of real-time androgen receptor alteration monitoring on metastatic castration-resistant prostate cancer treatment in real-world settings.

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.