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

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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 I–II clinical studies. All this makes it necessary to thoroughly study and describe each case of NEPC.

About the authors

Grigoriy A. Chizh

Petrov National Medicine Research Center of Oncology

Author for correspondence.
Email: ya.grisha234@yandex.ru
ORCID iD: 0000-0002-4979-3246

Medical Resident

Russian Federation, Saint Petersburg

Yuliya A. Tyutrina

Saint Petersburg State Pediatric Medical University

Email: ya.grisha234@yandex.ru
ORCID iD: 0000-0003-4279-9933

Medical Resident

Russian Federation, Saint Petersburg

Svetlana A. Protsenko

Petrov National Medicine Research Center of Oncology

Email: ya.grisha234@yandex.ru
ORCID iD: 0000-0001-6822-9467

D. Sci. (Med.), Prof.

Russian Federation, Saint Petersburg

Ernest S. Dzhelialov

Saint Petersburg State University

Email: ya.grisha234@yandex.ru
ORCID iD: 0000-0002-2571-243X

oncologist

Russian Federation, Saint Petersburg

Dilorom H. Latipova

Petrov National Medicine Research Center of Oncology; Saint Petersburg State Pediatric Medical University

Email: ya.grisha234@yandex.ru
ORCID iD: 0000-0002-8906-0370

oncologist

Russian Federation, Saint Petersburg; Saint Petersburg

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Supplementary files

Supplementary Files
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1. JATS XML
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2. Fig. 1. The data of OS in patients with small cell neuroendocrine prostate cancer (NEPC) [14].

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3. Fig. 2. Schematic representation of the proto-oncogenic effect of serine/threonine protein kinase (AURKA), which shows the epithelial-mesenchymal transition [16].

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4. Fig. 3. The illustration of the proto-oncogenic role of AURKA, expressed in stabilization of N-myc proto-oncogene, which acts as the transcription factor of CDK2, CDK4, CCND1 and CCNE1 genes expression, which determines the course of the cell through the cell cycle [17].

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5. Fig. 4. OS depending on the nature of molecular genetic disorders in case of NEPC. The alteration in Rb1 and TP53 is the most adverse effects in terms of prognosis [12].

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6. Fig. 5. OS of patients with different variants of NEPCs [25].

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7. Fig. 6. Magnetic resonance imaging scans after 2 months of being on the treatment. There is the appearance of the enlargement of the of the left iliac lymph nodes conglomerate (upper left and lower slide), extracapsular spread in prostate without involving the rectum and bladder (upper right slide).

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8. Fig. 7. CT of the abdomen after 2 months of treatment. There is the appearance of a tumor lesion of the tail of the pancreas (upper left slide), the involvement of the para-gastric lymph nodes (lower left slide), the enlargement of the iliac lymph nodes conglomerate associated with the compression of the left ureter (upper right slide), the development of left hydronephrosis with the enlargement of calices-pelvis system (lower right slide).

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9. Fig. 8. Tumor dynamics in the para-gastric lymph nodes.

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10. Fig. 9. There is a significant decrease of the tumor conglomerate mass of the iliac lymph nodes.

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