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AR alterations inform circulating tumor DNA detection in metastatic castration resistant prostate cancer patients
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AR alterations inform circulating tumor DNA detection in metastatic castration resistant prostate cancer patients
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Journal Article
AR alterations inform circulating tumor DNA detection in metastatic castration resistant prostate cancer patients
2024
Overview
Circulating tumor DNA (ctDNA) in plasma cell free DNA (cfDNA) of cancer patients is associated with poor prognosis, but is challenging to detect from low plasma volumes. In metastatic castration-resistant prostate cancer (mCRPC), ctDNA assays are needed to prognosticate outcomes of patients treated with androgen receptor (AR) inhibitors. We develop a custom targeted cfDNA sequencing assay, named
AR
-ctDETECT, to detect ctDNA in limiting plasma cfDNA available from mCRPC patients in the Alliance A031201 randomized phase 3 trial of enzalutamide with or without abiraterone. Of 776 patients, 59% are ctDNA-positive, with 26% having high ctDNA aneuploidy and 33% having low ctDNA aneuploidy but displaying
AR
gain or structural rearrangement,
MYC
/
MYCN
gain, or a pathogenic mutation. ctDNA-positive patients have significantly worse median overall survival than ctDNA-negative patients (29.0 months vs. 47.4 months, respectively). Here, we show that mCRPC patients identified as ctDNA-positive using the
AR
-ctDETECT assay have poor survival despite treatment with potent AR inhibitors in a phase 3 trial.
Liquid biopsy assays are important to prognosticate outcomes of metastatic castration-resistant prostate cancer (mCRPC) patients treated with androgen receptor (AR) inhibitors. Here this group reports detecting circulating tumor DNA in limiting plasma cell-free DNA of mCRPC patients as prognostic marker of poor survival after AR treatment.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 45/23
/ Aged
/ Androstenes - therapeutic use
/ Assaying
/ Benzamides - therapeutic use
/ Biomarkers, Tumor - genetics
/ Biopsy
/ Circulating Tumor DNA - blood
/ Circulating Tumor DNA - genetics
/ DNA
/ Humanities and Social Sciences
/ Humans
/ Male
/ Mutation
/ Phenylthiohydantoin - therapeutic use
/ Plasma
/ Prostatic Neoplasms, Castration-Resistant - blood
/ Prostatic Neoplasms, Castration-Resistant - drug therapy
/ Prostatic Neoplasms, Castration-Resistant - genetics
/ Prostatic Neoplasms, Castration-Resistant - pathology
/ Receptors, Androgen - genetics
/ Science
/ Survival
/ Tumors
