Study Characterizes Molecular Profile of Neuroendocrine Prostate Cancer

CHICAGO–Neuroendocrine prostate cancer is characterized by a molecular profile defined by distinct genomic alterations and decreased androgen receptor signaling, data presented at the 2015 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, IL, have shown.

Patients with neuroendocrine prostate cancer often have an aggressive clinical course and poor overall survival due to androgen receptor independence.  For the study, researchers performed whole-exome sequencing of 124 metastatic tumors from 81 patients. Of those, 35 had morphological features of neuroendocrine prostate cancer.

Results showed that the mutational landscape of castration-resistant prostate cancer and neuroendocrine prostate cancer did not significantly differ in the rate of non-synonymous mutations or copy number burden; however, RB1 loss (70% vs. 32%; P=0.003) and TP53 mutation or deletion (66.6% vs. 31.4%; P=0.04) were more common in neuroendocrine prostate cancer than castration-resistant disease.

The study also demonstrated that there was decreased androgen receptor signaling in neuroendocrine prostate cancer and a range of androgen receptor signaling in castration-resistant disease. Androgen receptor point mutations were absent in neuroendocrine disease and androgren receptor amplification was higher and more focal in castration-resistant disease (P=0.0075).

“Genomic changes did not fully explain the transition from CRPC to NEPC,” Himisha Beltran, MD, assistant professor of medicine at Weill Cornell Medical College in New York, NY, said during the presentation. Researchers also identified an 81 gene classifier of neuroendocrine prostate cancer by integrating key distinguishing features.

“Neuroendocrine prostate cancer can be distinguished from castration-resistant prostate cancer based on distinct molecular alterations, which are primarily epigenetic,” Dr. Beltran concluded. “These alterations are shared with a subset of castration-resistant disease, which may help identify patients with androgen receptor independence or those at high risk for progression.”

The findings ultimately provide new insight into neuroendocrine prostate cancer biology,  heterogenicity, and tumor evolution.

Reference

1. Beltran H, Prandi D, Mosquera JM, et al. Defining a molecular subclass of treatment resistant prostate cancer. J Clin Oncol. 2015;33:(suppl; abstr 5004).