AR alterations inform circulating tumor DNA detection in metastatic castration resistant prostate cancer patients Journal Article
| Authors: | Knutson, T. P.; Luo, B.; Kobilka, A.; Lyman, J.; Guo, S.; Munro, S. A.; Li, Y.; Heer, R.; Gaughan, L.; Morris, M. J.; Beltran, H.; Ryan, C. J.; Antonarakis, E. S.; Armstrong, A. J.; Halabi, S.; Dehm, S. M. |
| Article Title: | AR alterations inform circulating tumor DNA detection in metastatic castration resistant prostate cancer patients |
| Abstract: | 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. © The Author(s) 2024. |
| Keywords: | survival; controlled study; aged; middle aged; human cell; major clinical study; overall survival; genetics; mutation; androgen; prednisone; clinical trial; cancer patient; metastasis; progression free survival; randomized controlled trial; pathology; tumor marker; plasma cell; blood; dna; neoplasm metastasis; genomics; androgen receptor; phase 3 clinical trial; abiraterone acetate; castration; receptors, androgen; tumor; drug therapy; aneuploidy; nitriles; nitrile; gene structure; castration resistant prostate cancer; phenylthiohydantoin; ar protein, human; cell; benzamide derivative; benzamides; abiraterone; clinical outcome; cancer prognosis; enzalutamide; plasma volume; dna sequencing; cancer; humans; prognosis; human; male; article; circulating tumor dna; prostatic neoplasms, castration-resistant; metastatic castration resistant prostate cancer; androstane derivative; biomarkers, tumor; androstenes |
| Journal Title: | Nature Communications |
| Volume: | 15 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-12-11 |
| Start Page: | 10648 |
| Language: | English |
| DOI: | 10.1038/s41467-024-54847-1 |
| PUBMED: | 39663356 |
| PROVIDER: | scopus |
| PMCID: | PMC11634963 |
| DOI/URL: | |
| Notes: | Source: Scopus |
