Circulating cell-free AR and CYP17A1 copy number variations may associate with outcome of metastatic castration-resistant prostate cancer patients treated with abiraterone

Abstract

Background:This study aimed to investigate copy number variations (CNVs) of CYP17A1 and androgen receptor (AR) genes in serum cell-free DNA collected before starting abiraterone in 53 consecutive patients with castration-resistant prostate cancer (CRPC).Methods:Serum DNA was isolated and CNVs were analysed for AR and CYP17A1 genes using Taqman copy number assays. The association between CNVs and progression-free/overall survival (PFS/OS) was evaluated by the Kaplan–Meier method and log-rank test.Results:Median PFS of patients with AR gene gain was 2.8 vs 9.5 months of non-gained cases (P<0.0001). Patients with CYP17A1 gene gain had a median PFS of 2.8 months vs 9.2 months in the non-gained patients (P=0.0014). A lower OS was reported in both cases (AR: P<0.0001; CYP17A1: P=0.0085). Multivariate analysis revealed that PSA decline ⩾50%, AR and CYP17A1 CNVs were associated with shorter PFS (P<0.0001, P=0.0004 and P=0.0450, respectively), while performance status, PSA decline ⩾50%, AR CNV and DNA concentration were associated with OS (P=0.0021, P=0.0014, P=0.0026 and P=0.0129, respectively).Conclusions:CNVs of AR and CYP17A1 genes would appear to be associated with outcome of CRPC patients treated with abiraterone.

Genomic alterations in plasma DNA from patients with metastasized prostate cancer receiving abiraterone or enzalutamide

“…Additionally, gain of CYP17A1 has been associated with reduced progression-free survival (PFS) in men receiving abiraterone treatment 14 and loss of RB1 has predicted worse PFS in men treated with enzalutamide 16 . Only a few studies have employed genome-wide approaches of plasma DNA analyses in prostate cancer 11, 13, 18, 19 .…”

Targeting the androgen receptor in metastatic castrate-resistant prostate cancer: A review

“…A recent study published by Azad et al [42] used cell-free DNA analyses from patients treated with either enzautamide or abiraterone to demonstrate that patients with an AR gene aberration, defined as copy number variation or mutation in exon 8, had poorer clinical outcomes, lower rates of PSA decline, and shorter time to progression. Another study by Salvi et al [43] demonstrated similar results when looking at AR copy number variation and mutations in the CYP17A gene in patients treated with abiraterone.…”

Neueste technologische Entwicklungen für die Analyse von zirkulierender Tumor-DNA

“…Bei Patienten mit Prostatakarzinom unter Hormontherapie konnte anhand von ctDNA-Analysen eine Assoziation zwischen dem Vorliegen von bestimmten SCNAs und dem klinischen Outcome gezeigt werden [105]. Die vermehrte Entstehung von fokalen Amplifikationen in fortgeschrittenen Stadien, was auf eine hohe Plastizität der Tumore hindeutet, konnte von uns kürzlich aus dem Plasma nachgewiesen werden [80].…”