Current concepts of neuroendocrine cancer of the prostate: a clinical case and review of the literature

Abstract

Prostate cancer (PC) is a heterogeneous group of diseases that differ in their biological nature, clinical manifestations, and prognosis. A special variant among them is a neuroendocrine prostate cancer (NEPC). NEPC is a rare disease with unfavorable prognosis. The majority of patients with different NEPC variants die within 2 years after the diagnosis, despite the performed treatment. The distinctive features of NEPC are the patterns of metastasis in the form of a tendency to involve internal organs and extra regional lymph nodes, lytic bone lesions; high rates (up to 6 months) of clinical and radiological disease progression against the background of androgen-deprivation therapy; expression of serological markers and their high content in peripheral blood. The reasons of the aggressive behavior of NEPC consists in molecular and genetic events in cells, leading to realization of androgen-independent mechanisms of proliferation as a result of the AURKA-mediated neuroendocrine differentiation of tumor cells, early loss of function of p53 and Rb1 oncosuppressors, and low expression of androgen receptors. In every tenth case of NEPC, these molecular changes are response of prostatic adenocarcinoma to androgen-deprivation therapy. The described clinical case demonstrates the differences of biological behavior of these cancer variants and their sensitivity to various variants of drug treatment. Our case also illustrates possible difficulties of differential diagnostics of prostatic adenocarcinoma with various variants of neuroendocrine cancer, especially with adenocarcinoma with foci of neuroendocrine differentiation. The complexity of management of patients with NEPC are exacerbated by insufficient coverage of this problem: the existing data on the management of patients suffering from various variants of NEPC are limited by descriptions of clinical cases, literature reviews and few phases III clinical studies. All this makes it necessary to thoroughly study and describe each case of NEPC.