Transcriptional Profiles From Liquid Biopsy: A Prognostic Marker in Metastatic Prostate Cancer?
Posted: Monday, August 16, 2021
Liquid biopsies taken from circulating tumor cells in patients with metastatic prostate cancer may contain a transcriptional profile that appears to have independent prognostic value, according to prospective research presented in the Journal of Clinical Oncology. Jamie M. Sperger, PhD, of the University of Wisconsin, Madison, and colleagues used the novel biopsy method to evaluate the expression of androgen receptor splice variants, androgen receptor targets, and neuroendocrine prostate cancer markers.
“To our knowledge, we demonstrate the first multiplex gene expression liquid biopsy assay that can assess multiple potential [androgen receptor signaling inhibitor] resistance mechanisms simultaneously in metastatic prostate cancer,” concluded the study investigators. “Early identification of these molecular changes could help guide treatment decisions.”
The study included a prospective cohort of 99 men. Liquid biopsies were performed to analyze patterns of gene expression, and two distinct clusters of circulating tumor cell transcripts were observed. Cluster 1 was characterized by low to absent detection of androgen receptor–regulated genes, whereas cluster 2 was found to be a prognostic marker for a rise in the expression of androgen receptor–regulated genes and poorer overall survival (median 8.6 vs. 22.4 months in cluster 1). Additional clinicopathologic variables did not appear to impact the prognostic value of cluster 2.
Findings from this study were validated using two prospective multicenter phase II clinical trials of androgen receptor signaling inhibitors in patients with castration-resistant prostate cancer. One trial included 21 patients treated with enzalutamide, and the other included 27 patients treated with abiraterone. Upon validation, associations between cluster 2 and poorer overall survival (15.2 months vs. not reached), prostate-specific antigen progression-free survival (3.6 vs. 12 months), and radiographic progression-free survival (2.7 vs. 40.6 months) were observed.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.