Современные представления о нейроэндокринном раке предстательной железы: клинический случай и обзор литературы

Чиж Г.А., Тютрина Ю.А., Проценко С.А., Джелялов Э.С., Латипова Д.Х. Современные представления о нейроэндокринном раке предстательной железы: клинический случай и обзор литературы. Современная Онкология. 2022;24(2):242–249. DOI: 10.26442/18151434.2022.2.201242

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Chizh GA, Tyutrina YuA, Protsenko SA, Dzhelialov ES, Latipova DH. Current concepts of neuroendocrine cancer of the prostate: a clinical case and review of the literature. Journal of Modern Oncology. 2022;24(2):242–249.
DOI: 10.26442/18151434.2022.2.201242

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Аннотация

Рак предстательной железы (РПЖ) является неоднородной группой заболеваний, которые различаются по своей биологической природе, клиническому течению и прогнозу. Особенным вариантом среди них является нейроэндокринный РПЖ (НЭРПЖ) – редкое и прогностически неблагоприятное заболевание. Большинство больных с различными вариантами НЭРПЖ умирают в течение 2 лет после постановки данного диагноза, несмотря на проводимое лечение. Отличительными особенностями НЭРПЖ являются характер метастазирования в виде тенденции к поражению внутренних органов и внерегионарных лимфатических узлов, литическому поражению костей; высокие темпы (до 6 мес) клинического и радиологического прогрессирования заболевания на фоне андрогендепривационной терапии; экспрессии серологических маркеров и их высокое содержание в периферической крови. Причины агрессивного течения НЭРПЖ заключаются в молекулярно-генетических событиях, а именно реализации андрогеннезависимых механизмов пролиферации опухолевых клеток. Данные механизмы сводятся к AURKA-опосредованной нейроэндокринной дифференцировке опухолевых клеток, ранней утрате функции онкосупрессоров р53 и Rb1 и низкой экспрессии андрогеновых рецепторов. В каждом десятом случае данные изменения являются ответом аденокарциномы предстательной железы на проводимую андрогендепривационную терапию. Описанный клинический случай демонстрирует различия биологического поведения данных вариантов рака и их чувствительности к различным вариантам лекарственного лечения, а также иллюстрирует возможные сложности дифференциальной диагностики аденокарциномы предстательной железы с различными вариантами нейроэндокринного рака, в особенности с аденокарциномой с очагами нейроэндокринной дифференцировки. Сложность ведения пациентов с НЭРПЖ усугубляется недостаточной освещенностью данной проблемы: существующие данные о ведении пациентов, страдающих различными вариантами НЭРПЖ, ограничены описаниями клинических случаев, литературных обзоров и немногочисленными клиническими исследованиями I–II фазы. Все это делает необходимым тщательное изучение и описание каждого случая НЭРПЖ.

Ключевые слова: нейроэндокринный рак предстательной железы, нейроэндокринная трансдифференцировка, аденокарцинома предстательной железы

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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.

Keywords: neuroendocrine prostate cancer, neuroendocrine transdifferentiation, prostate adenocarcinoma

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Список литературы

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________________________________________________

1. Abbas F, Civantos F, Benedetto P, et al. Small cell carcinoma of the bladder and prostate. Urology. 1995;46(5):617-30.
2. Sivkov AV, Keshishev NG, Efremov GD, et al. Neiroendokrinnaia differentsirovka raka predstatel'noi zhelezy, chto novogo? Eksperimental'naia i klinicheskaia urologiia. 2015;3:22‑30 (in Russian).
3. Beltran H, Demichelis F. Therapy considerations in neuroendocrine prostate cancer: what next? Endocr Relat Cancer. 2021;28(8):T67-78. DOI:10.1530/ERC-21-0140
4. Deng X, Liu H, Huang J, et al. Ionizing radiation induces prostate cancer neuroendocrine differentiation through interplay of CREB and ATF2: Implications for disease progression. Cancer Res. 2008;68:9663-70. DOI:10.1158/0008-5472.CAN-08-2229
5. Patel GK, Chugh N, Tripathi M. Neuroendocrine Differentiation of Prostate Cancer – An Intriguing Example of Tumor Evolution at Play. Cancers (Basel). 2019;11(10):1405.
6. Zhang Q, Han Y, Zhang Y, et al. Treatment-Emergent Neuroendocrine Prostate Cancer: A Clinicopathological and Immunohistochemical Analysis of 94 Cases. Front Oncol. 2021;10:571308. DOI:10.3389/fonc.2020.571308
7. Epstein JI, Amin MB, Beltran H, et al. Proposed morphologic classification of prostate cancer with neuroendocrine differentiation. Am J Surg Pathol. 2014;38(6):756-67.
8. Beltran H, Tomlins S, Aparicio A, et al. Aggressive variants of castration-resistant prostate cancer. Clin Cancer Res. 2014;20(11):2846-50. DOI:10.1158/1078-0432.CCR-13-3309
9. Abbasova DV. Neiroendokrinnye opukholi redkikh lokalizatsii. Dis. … kand. med. nauk. Moscow, 2020 (in Russian).
10. Di Sant'Agnese PA. Neuroendocrine cells of the prostate and neuroendocrine differentiation in prostatic carcinoma: a review of morphologic aspects. Urology. 1998;51(5A Suppl.):121-4. DOI:10.1016/s0090-4295(98)00064-8
11. Chughtai B, Forde J, Thomas D, et al. Benign prostatic hyperplasia. Nat Rev Dis Primers. 2016;2:16031.
12. Abida W, Cyrta J, Heller G, et al. Genomic correlates of clinical outcome in advanced prostate cancer. Proc Natl Acad Sci USA. 2019;116(23):11428-36.
13. Beltran H, Rickman DS, Park K, et al. Molecular Characterization of Neuroendocrine Prostate Cancer and Identification of New Drug Targets. Cancer Discov. 2011;1(6): 487‑95. DOI:10.1158/2159-8290.CD-11-0130
14. Aggarwal R, Huang J, Alumkal JJ, et al. Clinical and Genomic Characterization of Treatment-Emergent Small-Cell Neuroendocrine Prostate Cancer: A Multi-institutional Prospective Study. J Clin Oncol. 2018;36(24):2492-503.
15. Zhou H, Kuang J, Zhong L, et al. Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nat Genet. 1998;20:189‑93.
16. D`Assoro AB, Haddad T, Galanis E. Aurora-A Kinase as a Promising Therapeutic Target in Cancer. Front Oncol. 2016;5:295.
17. Terry S, Beltran H. The Many Faces of Neuroendocrine Differentiation in Prostate Cancer Progression. Published online 2014 Mar 25. Prepublished online 2014 Mar 3.
18. Wu CH, Lan YJ, Wang CH, Wu MS. Hypercalcemia in prostate cancer with positive neuron-specific enolase stain. Ren Fail. 2004;26(3):325-7.
19. Hindson DA, Knight LL, Ocker JM. Small-cell carcinoma of prostate. Transient complete remission with chemotherapy. Urology. 1985;26:182-4.
20. Bhandari R, Vengaloor TT, Giri S, et al. Small Cell Carcinoma of the Prostate: A Case Report and Review of the Literature. Cureus. 2020;12(2):e7074.
21. Furtado P, Lima MV, Nogueira C, et al. Review of small cell carcinomas of the prostate. Prostate Cancer. 2011;2011:543272.
22. Amato RJ, Logothetis CJ, Hallinan R, et al. Chemotherapy for small cell carcinoma of prostatic origin. J Urol. 1992;147:935-7.
23. Papandreou CN, Daliani DD, Thall PF, et al. Results of a phase II study with doxorubicin, etoposide, and cisplatin in patients with fully characterized small-cell carcinoma of the prostate. J Clin Oncol. 2002;20:3072-80.
24. Hager S, Ackermann CJ, Joerger M, et al. Anti-tumour activity of platinum compounds in advanced prostate cancer – a systematic literature review. Ann Oncol. 2016;27(6):975-84. DOI:10.1093/annonc/mdw156
25. Conteduca V, Oromendia C, Eng K, et al. Clinical features of neuroendocrine prostate cancer. Eur J Cancer. 2019;121:7-18. DOI:10.1016/j.ejca.2019.08.011
26. Krook JE, Jett JR, Little C. A Phase I-II Study of Sequential Infusion VP-16 and Cisplatin Therapy in Advanced Lung Cancer. Am J Clin Oncol. 1989;12:114-7.
DOI:10.1097/00000421-198904000-00005
27. Moertel CG, Kvols LK, O’Connell MJ, Rubin J. Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin. Evidence of major therapeutic activity in the anaplastic variants of these neoplasms. Cancer. 1991;68:227-32.
28. Caubet M, Dobi E, Pozet A, et al. Carboplatin-etoposide combination chemotherapy in metastatic castration-resistant prostate cancer: A retrospective study. Mol Clin Oncol. 2015;6:1208-12. DOI:10.3892/mco.2015.628
29. Fjällskog ML, Granberg DP, Welin SL, et al. Treatment with cisplatin and etoposide in patients with neuroendocrine tumors. Cancer. 2001;92:1101-7.
30. Horn L, Mansfield AS, Szczęsna A, et al; IMpower133 Study Group. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018;379:2220-9.
31. Petrylak DP, Tangen CM, Hussain MH, et al. Docetaxel and Estramustine Compared with Mitoxantrone and Prednisone for Advanced Refractory Prostate Cancer. N Engl J Med. 2004;351:1513-20.
32. Tannock IF, De Wit R, Berry WR, et al. Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer. N Engl J Med. 2004;351:1502-12.
33. Smyth J, Smith I, Sessa C, et al. Activity of docetaxel (Taxotere) in small cell lung cancer. The Early Clinical Trials Group of the EORTC. Eur J Cancer. 1994;30:1058‑60. DOI:10.1016/0959-8049(94)90455-3.
34. Hesketh PJ, Crowley JJ, Burris HA, et al. Evaluation of docetaxel in previously untreated extensive-stage small cell lung cancer: A Southwest Oncology Group phase II trial. Cancer J Sci Am. 1999;5:237-41. PMID: 10439170.
35. Aparicio AM, Harzstark AL, Corn PG, et al. Platinum-Based Chemotherapy for Variant Castrate-Resistant Prostate Cancer. Clin Cancer Res. 2013;19:3621-30.
DOI:10.1158/1078-0432.CCR-12-3791
36. Corn PG, Heath E, Zurita A, et al. Cabazitaxel plus carboplatin for the treatment of men with metastatic castration-resistant prostate cancers: A randomised, open-label, phase 1–2 trial. Lancet Oncol. 2019;20:1432-43.
37. Aggarwal R, Huang J, Alumkal JJ, et al. Clinical and Genomic Characterization of Treatment-Emergent Small-Cell Neuroendocrine Prostate Cancer: A Multi-institutional Prospective Study. J Clin Oncol. 2018;36:2492-503.
38 Guedes LB, Antonarakis ES, Schweizer MT, et al. MSH2 Loss in Primary Prostate Cancer. Clin Cancer Res. 2017;23(22):6863-74.
39. Wagner DG, Gatalica Z, Lynch HT, et al. Neuroendocrine-Type Prostatic Adenocarcinoma with Microsatellite Instability in a Patient With Lynch Syndrome. Int J Surg Pathol. 2010;18:550-3.
40. Puca L, Gayvert K, Sailer V, et al. Delta-like protein 3 expression and therapeutic targeting in neuroendocrine prostate cancer. Sci Transl Med. 2019;11:eaav0891.
41. Rudin CM, Pietanza MC, Bauer TM, et al. Rovalpituzumab tesirine, a DLL3‑targeted antibody-drug conjugate, in recurrent small-cell lung cancer: a first-in-human, first-in-class, open-label, phase 1 study. Lancet Oncol. 2017;18(1):42-51. DOI:10.1016/S1470-2045(16)30565-4
42. Spetsieris N, Boukovala M, Patsakis G, et al. Neuroendocrine and Aggressive-Variant Prostate Cancer. Cancers (Basel). 2020;12(12):3792.
43. Fléchon A, Pouessel D, Ferlay C, et al. Phase II study of carboplatin and etoposide in patients with anaplastic progressive metastatic castration-resistant prostate cancer (mCRPC) with or without neuroendocrine differentiation: results of the French Genito-Urinary Tumor Group (GETUG) P01 trial. Ann Oncology. 2011;22(11)2476481.
44. Walia G, Pienta KJ, Simons JW, Soule HR. The 19th annual Prostate Cancer Foundation scientific retreat. Cancer Res. 2013;73(16):4988-91. DOI:10.1158/0008-5472.CAN-12-4576
45. Tang A, Keu Gao K, Chu L, et al. Aurora kinases: novel therapy targets in cancers. Oncotarget. 2017;8(14):23937-54. doi:10.18632/oncotarget.14893

Авторы

Г.А. Чиж*1, Ю.А. Тютрина2, С.А. Проценко1, Э.С. Джелялов3, Д.Х. Латипова1,2

1 ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Петрова» Минздрава России, Санкт-Петербург, Россия;
2 ФГБОУ ВО «Санкт-Петербургский государственный педиатрический медицинский университет» Минздрава России, Санкт-Петербург, Россия;
3 ФГБОУ ВО «Санкт-Петербургский государственный университет», Санкт-Петербург, Россия
*ya.grisha234@yandex.ru

________________________________________________

Grigoriy A. Chizh*1, Yuliya A. Tyutrina2, Svetlana A. Protsenko1, Ernest S. Dzhelialov3, Dilorom H. Latipova1,2

1 Petrov National Medicine Research Center of Oncology, Saint Petersburg, Russia;
2 Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia;
3 Saint Petersburg State University, Saint Petersburg, Russia
*ya.grisha234@yandex.ru

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