Phenotypic characterization of circulating tumor cells (CTCs) from neuroendocrine prostate cancer (NEPC) and metastatic castration-resistant prostate cancer (mCRPC) patients to identify a novel diagnostic algorithm for the presence of NEPC.

Abstract

197 Background: NEPC is an aggressive variant of prostate cancer that most commonly arises in later stages of mCRPC, especially with visceral metastases in the setting of a low PSA. There are no reliable serum markers to identify patients that are transforming to NEPC and incidence of CTCs in these patients is unknown. Detection of NEPC has clinical implications as these patients are often treated with platinum chemotherapy rather than with androgen receptor (AR) targeted therapies such as abiraterone or enzalutamide. We sought to determine if phenotypic characterization of CTCs could differentiate NEPC from mCRPC. Methods: 24 pts (16 pts with tissue confirmed NEPC and 8 pts with mCRPC) had blood collection for CTC analysis utilizing the Epic Sciences platform. Epic analysis included identification of traditional CTCs (CK+, CD45- cells, with intact nuclei, morph distinct), CK- CTCs (CK-, CD45-, intact nuclei, morph distinct), small CTCs (CK+, CD45-, intact nuclei, small cell size), and CTC clusters. We examined CTCs at the single cell level for CTC size, shape, epithelial and AR expression. Advanced digital pathology algorithms measured size and shape measurements of CTCs. Results: CTCs from NEPC patients demonstrated strong statistical differentiation from mCRPC patients, with unique CTC morphology and protein chemistry that was not seen in mCRPC CTCs. NEPC CTCs had increase prevalence of unique CTC phenotypes including: small size, AR negativity, and presence of nucleoli. Unique cell types enabled a multivariate biomarker that is strongly associated with CTCs exclusive to tissue confirmed NEPC. Conclusions: CTCs from NEPC have unique phenotypes compared with those from mCRPC. If confirmed, the utilization of a liquid biopsy to diagnose NEPC may enable earlier identification of patients prone to visceral metastasis, and intervention to cytotoxic therapeutics. Additionally, identification of patients with NEPC could help for patient selection for AR vs. NEPC targeted therapeutics. [Table: see text]