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Research Letter
May 2, 2019

Androgen Receptor Burden and Poor Response to Abiraterone or Enzalutamide in TP53 Wild-Type Metastatic Castration-Resistant Prostate Cancer

Author Affiliations
  • 1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • 2Center for Oncological Research (CORE), University of Antwerp, Antwerp, Belgium
  • 3Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom
  • 4Department of Oncology, GZA Hospitals Sint-Augustinus, Antwerp, Belgium
  • 5Department of Medical Epidemiology and Biostatistics, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden
JAMA Oncol. Published online May 2, 2019. doi:10.1001/jamaoncol.2019.0869

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.

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