Androgen receptor (AR) molecular perturbations in liquid biopsy specimens (circulating tumor cells [CTCs] and circulating tumor DNA [ctDNA]) from patients with metastatic castration-resistant prostate cancer (mCRPC) are associated with poorer outcomes on the AR signaling inhibitors (ARSis) abiraterone or enzalutamide, with contradictory claims regarding the clinical use of AR splice variant 7 (AR-V7) or AR amplification status.1-4 By using comprehensive liquid biopsy AR profiling,5 we previously demonstrated how AR perturbations lost prognostic value when correcting for tumor burden estimates and clinical variables.6 Consistent with others’ findings,4 we observed that AR-driven biomarkers were outperformed by TP53 alterations, noting that 71.3% and 97.9% of patients carried relevant AR-driven biomarkers at baseline and progression, respectively.6 We therefore speculate that long-term chemical castration, alongside the cancer treatment trajectory, will eventually lead to perturbed AR biomarker output in all patients. In this scenario, multiple biomarker assessments of AR are necessary to identify ARSi-sensitive patients.
De Laere B, Rajan P, Grönberg H, Dirix L, Lindberg J, for the CORE-ARV-CTC and ProBIO Investigators. Androgen Receptor Burden and Poor Response to Abiraterone or Enzalutamide in TP53 Wild-Type Metastatic Castration-Resistant Prostate Cancer. JAMA Oncol. Published online May 02, 2019. doi:10.1001/jamaoncol.2019.0869
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