Molecular characterization of circulating tumor cells (CTCs) of patients with neuroendocrine prostate cancer (NEPC).

Abstract

177 Background: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that commonly arises in later stages of castration resistant prostate cancer (CRPC), especially with visceral metastases in the setting of a low prostate-specific antigen (PSA). The genes AURKA and MYCNare frequently amplified. There are no reliable serum markers to identify patients that are transforming to NEPC and incidence of circulating tumor cells (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. Methods: Ten men with metastatic NEPC underwent metastatic tumor biopsy and blood collection for CTC analysis utilizing the Epic Sciences platform. Clinical characteristics, pathologic and molecular features including exome sequencing of metastatic tumors, serum PSA and neuroendocrine (NE) markers, CTC count by CellSearch were obtained on all patients. AURKA and MYCNamplification were assessed by FISH in both tumors and Epic CTCs. Results: Sites of metastases included liver (6 out of 10), bone (9 out of 10), lymph nodes (8 out of 10), pleura (1 out of 10), and lungs (2 out of 10). Serum PSA, CellSearch CTCs, and serum NE markers were variable including 4 out of 10 patients with PSA less than 1 ng/ml (range 0.02-9.39) and 3 out of 5 evaluated patients with CTC count of zero (range 0 to 94). Four out of 7 evaluated tumors displayed amplification of AURKA and MYCN. Epic CTCs demonstrated frequent clusters, dim/low cytokeratin suggesting epithelial plasticity, and low AR expression. Patients were subsequently treated with platinum (4 out of 10), AURKAinhibitor (4 out of 10), or hormonal therapy (2 out of 10). Conclusions: PSA, serum NE markers, and CTC count by CellSearch may not be reliable in identifying patients with CRPC that have NE features. Epithelial plasticity potentially arising from epithelial-mesenchymal transition may explain lack of detection using conventional CTC assays. The Epic Sciences CTC platform is capable of detecting CTCs from patients with NEPC and CTCs are molecularly similar to metastatic biopsies. Epic CTCs may be useful in the earlier detection of NEPC and inform patient selection for therapy.