Skip to main content
SpringerLink
Log in

Das neuroendokrine Prostatakarzinom

Neuroendocrine prostate cancer

  • Übersichten
  • Published:
Der Urologe Aims and scope Submit manuscript

Zusammenfassung

Hintergrund

Das neuroendokrine Prostatakarzinom (NEPC) ist eine seltene, androgenunabhängige Variante des Prostatakarzinoms, welche aktuell in ihrer Inzidenz zunimmt. Das NEPC ist in der Regel rasch progredient und weist insgesamt eine schlechte Prognose auf. Aufgrund der unterschiedlichen Tumorbiologie des NEPC im Vergleich zum konventionellen Adenokarzinom der Prostata sind die klassischen Therapieansätze des Prostatakarzinoms meist nur bedingt wirksam. Eine effektive Therapie des NEPC existiert bis dato nicht.

Ziel der Arbeit

Die Übersicht zeigt histopathologische Charakteristika und die Klassifikation des NEPC sowie verfügbare und experimentelle Therapieansätze.

Material und Methoden

Die Literaturrecherche und Diskussion einzelner Studien befasst sich mit der oben genannten Fragestellung.

Ergebnisse

Aktuelle histopathologische Klassifikationen versuchen eine Unterscheidung zwischen dem NEPC und seinen Subtypen sowie dem Adenokarzinom der Prostata mit neuroendokriner Transdifferenzierung. Im Rahmen der konventionellen Chemotherapie wird nach wie vor eine platinbasierte Chemotherapie eingesetzt. Potenzielle Therapiealternativen stellen beispielsweise Angiogeneseinhibitoren dar, welche sich derzeit in der klinischen Erprobung befinden.

Schlussfolgerung

Die histomorphologischen Subtypen und Varianten des NEPC unterscheiden sich hinsichtlich Aggressivität, Prognose und Therapie. Die Therapie des NEPC differiert grundlegend von der des Adenokarzinoms der Prostata, unterliegt jedoch insgesamt einer schlechten Evidenz.

Abstract

Background

Neuroendocrine carcinoma of the prostate (NEPC) is a rare, androgen-independent variant of prostate cancer with increasing incidence of over the past few years. It commonly progresses rapidly and is associated with a poor prognosis. Based on a different tumor biology compared to adenocarcinomas of the prostate, standard therapeutic approaches for prostate cancer are ineffective. To date, no specific treatment for NEPC exists.

Objectives

The purpose of this work is to provide an overview of current histopathologic characteristics, histomorphologic classifications, and current as well as future treatment options for NEPC.

Materials and methods

The literature was reviewed and clinical trials focusing on the above mentioned objectives are discussed.

Results

Current histomorphologic classifications aim to differentiate between NEPC including its variants and neuroendocrine transdifferentiated adenocarcinoma of the prostate. Regarding conventional chemotherapy, platinum-based schemes are still widely used. Antiangiogenetic drugs represent potential alternatives and are currently under clinical investigation.

Conclusions

Histomorphological subtypes distinguish themselves in terms of aggressiveness, prognosis, and preferred therapeutic approaches. Treatment of NEPC differs fundamentally compared to adenocarcinoma of the prostate. There is only limited data available for the treatment of NEPC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1

Literatur

  1. Attard G, Sarker D, Reid A et al (2006) Improving the outcome of patients with castration-resistant prostate cancer through rational drug development. Br J Cancer 95(7):767–774

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Pienta KJ, Bradley D (2006) Mechanisms underlying the development of androgen-independent prostate cancer. Clin Cancer Res 12(6):1665–1671

    Article  PubMed  CAS  Google Scholar 

  3. di Sant’Agnese PA (2001) Neuroendocrine differentiation in prostatic carcinoma: an update on recent developments. Ann Oncol 12(Suppl 2):135–140

    Google Scholar 

  4. Abrahamsson PA (1999) Neuroendocrine cells in tumour growth of the prostate. Endocr Relat Cancer 6(4):503–519

    Article  PubMed  CAS  Google Scholar 

  5. di Sant’Agnese PA (1992) Neuroendocrine differentiation in human prostatic carcinoma. Hum Pathol 23(3):287–296

    Article  Google Scholar 

  6. Aprikian AG, Cordon-Cardo C et al (1993) Characterization of neuroendocrine differentiation in human benign prostate and prostatic adenocarcinoma. Cancer 71(12):3952–3965

    Article  PubMed  CAS  Google Scholar 

  7. DaSilva JO, Amorino GP, Casarez EV et al (2013) Neuroendocrine-derived peptides promote prostate cancer cell survival through activation of IGF-1R signaling. Prostate 73(8):801–812

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Tash JA, Reuter V, Russo P (2002) Metastatic carcinoid tumor of the prostate. J Urol 167(6):2526–2527

    Article  PubMed  Google Scholar 

  9. Beltran H, Rickman DS, Park K et al (2011) Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets. Cancer Discov 1(6):487–495

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Nelson EC, Cambio AJ, Yang JC et al (2007) Clinical implications of neuroendocrine differentiation in prostate cancer. Prostate Cancer Prostatic Dis 10(1):6–14

    Article  PubMed  CAS  Google Scholar 

  11. Cindolo L, Cantile M, Vacherot F et al (2007) Neuroendocrine differentiation in prostate cancer: from lab to bedside. Urol Int 79(4):287–296

    Article  PubMed  Google Scholar 

  12. Beltran H, Tagawa ST, Park K et al (2012) Challenges in recognizing treatment-related neuroendocrine prostate cancer. J Clin Oncol 30(36):386–389

    Article  Google Scholar 

  13. Aparicio AM, Harzstark AL, Corn PG et al (2013) Platinum-based chemotherapy for variant castrate-resistant prostate cancer. Clin Cancer Res 19(13):3621–330

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Pezaro CJ, Omlin A, Lorente D et al (2014) Visceral disease in castration-resistant prostate cancer. Eur Urol 65(2):270–273

    Article  PubMed  Google Scholar 

  15. Wang W, Epstein JI (2008) Small cell carcinoma of the prostate. A morphologic and immunohistochemical study of 95 cases. Am J Surg Pathol 32(1):65–71

    Article  PubMed  Google Scholar 

  16. Lotan TL, Gupta NS, Wang W et al (2011) ERG gene rearrangements are common in prostatic small cell carcinomas. Mod Pathol 24(6):820–828

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Tomlins SA, Rhodes DR, Perner S et al (2005) Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 310(5748):644–648

    Article  PubMed  CAS  Google Scholar 

  18. Mosquera JM, Mehra R, Regan MM et al (2009) Prevalence of TMPRSS2-ERG fusion prostate cancer among men undergoing prostate biopsy in the United States. Clin Cancer Res 15(14):4706–4711

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Williamson SR, Zhang S, Yao JL et al (2011) ERG-TMPRSS2 rearrangement is shared by concurrent prostatic adenocarcinoma and prostatic small cell carcinoma and absent in small cell carcinoma of the urinary bladder: evidence supporting monoclonal origin. Mod Pathol 24(8):1120–1127

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Scheble VJ, Braun M, Beroukhim R et al (2010) ERG rearrangement is specific to prostate cancer and does not occur in any other common tumor. Mod Pathol 23(8):1061–1067

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Santoni M, Conti A, Burattini L et al (2014) Neuroendocrine differentiation in prostate cancer: novel morphological insights and future therapeutic perspectives. Biochim Biophys Acta 1846(2):630–637

    PubMed  CAS  Google Scholar 

  22. Guo CC, Dancer JY, Wang Y et al (2011) TMPRSS2-ERG gene fusion in small cell carcinoma of the prostate. Hum Pathol 42(1):11–17

    Article  PubMed  CAS  Google Scholar 

  23. Beltran H, Tagawa ST, Park K et al (2014) Aggressive variants of castration-resistant prostate cancer. Clin Cancer Res 20(11):2846–2850

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Berruti A, Bollito E, Cracco CM et al (2010) The prognostic role of immunohistochemical chromogranin a expression in prostate cancer patients is significantly modified by androgen-deprivation therapy. Prostate 70(7):718–726

    PubMed  Google Scholar 

  25. Palmgren JS, Karavadia SS, Wakefield MR et al (2007) Unusual and underappreciated: small cell carcinoma of the prostate. Semin Oncol 34(1):22–29

    Article  PubMed  CAS  Google Scholar 

  26. Surcel CI, van Oort IM, Sooriakumaran P et al (2014) Prognostic effect of neuroendocrine differentiation in prostate cancer: a critical review. Urol Oncol 33(6):265.e1-7

    PubMed  Google Scholar 

  27. Epstein JI, Amin MB, Beltran H et al (2014) Proposed morphologic classification of prostate cancer with neuroendocrine differentiation. Am J Surg Pathol 38(6):756–767

    Article  PubMed  PubMed Central  Google Scholar 

  28. Parimi V, Goyal R, Poropatich K et al (2014) Neuroendocrine differentiation of prostate cancer: a review. Am J Clin Exp Urol 2(4):273–285

    PubMed  PubMed Central  Google Scholar 

  29. Marcus DM, Goodman M, Jani AB et al (2012) A comprehensive review of incidence and survival in patients with rare histological variants of prostate cancer in the United States from 1973 to 2008. Prostate Cancer Prostatic Dis 15(3):283–288

    Article  PubMed  CAS  Google Scholar 

  30. Mazzucchelli R, Morichetti D, Lopez-Beltran A et al (2009) Neuroendocrine tumours of the urinary system and male genital organs: clinical significance. BJU Int 103(11):1464–1470

    Article  PubMed  Google Scholar 

  31. Huang J, Yao JL, di Sant’agnese PA et al (2006) Immunohistochemical characterization of neuroendocrine cells in prostate cancer. Prostate 66(13):1399–1406

    Article  PubMed  CAS  Google Scholar 

  32. Yao JL, Madeb R, Bourne P et al (2006) Small cell carcinoma of the prostate: an immunohistochemical study. Am J Surg Pathol 30(6):705–712

    Article  PubMed  Google Scholar 

  33. Tan HL, Sood A, Rahimi HA et al (2014) Rb loss is characteristic of prostatic small cell neuroendocrine carcinoma. Clin Cancer Res 20(4):890–903

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Macleod KF (2010) The RB tumor suppressor: a gatekeeper to hormone independence in prostate cancer? J Clin Invest 120(12):4179–4182

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Deorah S, Rao MB, Raman R et al (2012) Survival of patients with small cell carcinoma of the prostate during 1973–2003: a population-based study. BJU Int 109(6):824–830

    Article  PubMed  Google Scholar 

  36. Mackey JR, Au HJ, Hugh J et al (1998) Genitourinary small cell carcinoma: determination of clinical and therapeutic factors associated with survival. J Urol 159(5):1624–1629

    Article  PubMed  CAS  Google Scholar 

  37. Evans AJ, Humphrey PA, Belani J et al (2006) Large cell neuroendocrine carcinoma of prostate: a clinicopathologic summary of 7 cases of a rare manifestation of advanced prostate cancer. Am J Surg Pathol 30(6):684–693

    Article  PubMed  Google Scholar 

  38. Hirano D, Okada Y, Minei S et al (2004) Neuroendocrine differentiation in hormone refractory prostate cancer following androgen deprivation therapy. Eur Urol 45(5):586–592

    Article  PubMed  CAS  Google Scholar 

  39. Berruti A, Tucci M, Mosca A et al (2007) Chromogranin A expression in patients with hormone naive prostate cancer predicts the development of hormone refractory disease. J Urol 178(3 Pt 1):838–843

    Article  PubMed  CAS  Google Scholar 

  40. Culine S, El Demery M, Lamy PJ et al (2007) Docetaxel and cisplatin in patients with metastatic androgen independent prostate cancer and circulating neuroendocrine markers. J Urol 178(3 Pt 1):844–848

    Article  PubMed  CAS  Google Scholar 

  41. Amato RJ, Logothetis CJ, Hallinan R et al (1992) Chemotherapy for small cell carcinoma of prostatic origin. J Urol 147(3 Pt 2):935–937

    PubMed  CAS  Google Scholar 

  42. Papandreou CN, Usmani B, Geng Y et al (2002) 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 20(14):3072–3080

    Article  PubMed  CAS  Google Scholar 

  43. Mazzucchelli R, Montironi R, Santinelli A et al (2000) Vascular endothelial growth factor expression and capillary architecture in high-grade PIN and prostate cancer in untreated and androgen-ablated patients. Prostate 45(1):72–79

    Article  PubMed  CAS  Google Scholar 

  44. Qiu Y, Robinson D, Pretlow TG et al (1998) Etk/Bmx, a tyrosine kinase with a pleckstrin-homology domain, is an effector of phosphatidylinositol 3’-kinase and is involved in interleukin 6-induced neuroendocrine differentiation of prostate cancer cells. Proc Natl Acad Sci USA 95(7):3644–3649

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Xie S, Lin HK, Ni J et al (2004) Regulation of interleukin-6-mediated PI3K activation and neuroendocrine differentiation by androgen signaling in prostate cancer LNCaP cells. Prostate 60(1):61–67

    Article  PubMed  CAS  Google Scholar 

  46. Angevin E, Tabernero J, Elez E et al (2014) A phase I/II, multiple-dose, dose-escalation study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with advanced solid tumors. Clin Cancer Res 20(8):2192–2204

    Article  PubMed  CAS  Google Scholar 

  47. Meulenbeld HJ, Bleuse JP, Vinci EM et al (2013) Randomized phase II study of danusertib in patients with metastatic castration-resistant prostate cancer after docetaxel failure. BJU Int 111(1):44–52

    Article  PubMed  CAS  Google Scholar 

  48. Beltran H, Rubin MA (2013) New strategies in prostate cancer: translating genomics into the clinic. Clin Cancer Res 19(3):517–523

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Molife LR, Yan L, Vitfell-Rasmussen J et al (2014) Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors. J Hematol Oncol 7(1):1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Carducci MA, Saad F, Abrahamsson PA et al (2007) A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer. Cancer 110(9):1959–1966

    Article  PubMed  CAS  Google Scholar 

  51. Liu X, Peng J, Sun W et al (2013) G31P, an antagonist against CXC chemokine receptors 1 and 2, inhibits growth of human prostate cancer cells in nude mice. Tohoku J Exp Med 228(2):147–156

    Article  CAS  Google Scholar 

Download references

Einhaltung ethischer Richtlinien

Interessenkonflikt. A. Kretschmer, C. Wittekind, C.G. Stief und C. Gratzke geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

Author information

Authors and Affiliations

  1. Urologische Klinik und Poliklinik, Klinikum der Universität München, Ludwig-Maximilians Universität München, Campus Großhadern, Marchioninistraße 15, 81377, München, Deutschland

    A. Kretschmer, C.G. Stief & C. Gratzke

  2. Institut für Pathologie, Universitätsklinikum Leipzig, Leipzig, Deutschland

    C. Wittekind

Authors
  1. A. Kretschmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Wittekind
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C.G. Stief
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Gratzke
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Kretschmer.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kretschmer, A., Wittekind, C., Stief, C. et al. Das neuroendokrine Prostatakarzinom. Urologe 54, 1779–1783 (2015). https://doi.org/10.1007/s00120-015-4015-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00120-015-4015-9

Schlüsselwörter

Keywords

Search

Navigation