Photo Credit: Mohammed Haneefa Nizamudeen
The following is a summary of “AR alterations inform circulating tumor DNA detection in metastatic castration resistant prostate cancer patients,” published in the December 2024 issue of Urology by Knutson et al.
Circulating tumor DNA (ctDNA) in plasma cell-free DNA (cfDNA) is linked to poor prognosis but is hard to detect in low volumes. In metastatic castration-resistant prostate cancer (mCRPC), ctDNA assays are vital for prognostication with androgen receptor (AR) inhibitor treatment.
Researchers conducted a retrospective study to assess the role of ctDNA in plasma cfDNA in mCRPC.
They developed the AR-ctDETECT assay to detect ctDNA in limited plasma cfDNA from patients with mCRPC in the Alliance A031201 phase 3 trial of enzalutamide with or without abiraterone. The assay was applied to 776 patients to evaluate ctDNA presence and its prognostic value.
The results showed that 59% of 776 patients were ctDNA-positive, with 26% showing high ctDNA aneuploidy and 33% having low aneuploidy with AR gain, structural rearrangement, MYC/MYCN gain, or a pathogenic mutation. ctDNA-positive patients had a median overall survival (OS) of 29.0 months compared to 47.4 months for ctDNA-negative patients.
Investigators found that patients with mCRPC identified as ctDNA-positive using the AR-ctDETECT assay had poor survival outcomes despite treatment with potent AR inhibitors in a phase 3 trial.