title: Characterization of prostate neuroendocrine cancers and therapeutic management: a literature review.
abstract: OBJECTIVE
  Neuroendocrine prostate cancers (NEPCs) are rare. The current lack of consensus for clinical, biological and pathological characterization as well as therapeutic approach makes the management of those tumors a clinical challenge. This literature review aims to summarize available data on the characterization and management of patients with prostate cancer with a neuroendocrine element. We try to identify major controversies and uncertainties in order to understand all aspects of this particular entity.
  
  
  METHODS
  We searched for all articles published and registered in the MEDLINE database before 31 November 2013 with the following search terms: (('prostatic neoplasms' (MeSH Terms)) AND ('carcinoma, neuroendocrine' (MeSH Terms)) OR ('carcinoma, small cell' (MeSH Terms))) AND (English (Language)).
  
  
  RESULTS
  Case reports, letters or comments were excluded. We then selected relevant articles from titles and abstracts. Overall, 278 articles published between 1976 and November 2013 were identified. No definition of NEPC seems to be clearly established. Natural history of the disease reveals poor prognosis with median survival of up to 10 to 13 months. Histological characterization appears difficult. Serum markers could be helpful with some controversies in terms of prognostic significance. Concerning management, the majority of patients received local treatment combined with chemotherapy in case of early and localized disease. Few clinical trials described strategy for metastatic disease.
  
  
  CONCLUSIONS
  The exploration of the different pathways implicated in the neuroendocrine differentiation of prostate cancers is essential for the comprehension of castration-resistance mechanisms. It will enable the identification of optimal therapeutic strategies for which no recommendation is currently established. Inclusion in prospective clinical trials appears necessary to identify the adequate strategy.
authors.affiliation: Primary Work, Institut Bergonie, Bordeaux, France.
authors.forename: P
authors.initials: P
authors.lastname: Sargos
authors.affiliation: Primary Work, Institut Bergonie, Bordeaux, France.
authors.forename: L
authors.initials: L
authors.lastname: Ferretti
authors.affiliation: Primary Work, Institut Bergonie, Bordeaux, France.
authors.forename: M
authors.initials: M
authors.lastname: Gross-Goupil
authors.affiliation: Primary Work, Institut Bergonie, Bordeaux, France.
authors.forename: M
authors.initials: M
authors.lastname: Orre
authors.affiliation: Primary Work, Institut Bergonie, Bordeaux, France.
authors.forename: F
authors.initials: F
authors.lastname: Cornelis
authors.affiliation: Primary Work, Institut Bergonie, Bordeaux, France.
authors.forename: B
authors.initials: B
authors.lastname: Henriques de Figueiredo
authors.affiliation: Primary Work, Institut Bergonie, Bordeaux, France.
authors.forename: N
authors.initials: N
authors.lastname: Houédé
authors.affiliation: Primary Work, Institut Bergonie, Bordeaux, France.
authors.forename: C
authors.initials: C
authors.lastname: Merino
authors.affiliation: Primary Work, Institut Bergonie, Bordeaux, France.
authors.forename: G
authors.initials: G
authors.lastname: Roubaud
authors.affiliation: Primary Work, Institut Bergonie, Bordeaux, France.
authors.forename: B
authors.initials: B
authors.lastname: Dallaudiére
authors.affiliation: Primary Work, Institut Bergonie, Bordeaux, France.
authors.forename: P
authors.initials: P
authors.lastname: Richaud
authors.affiliation: Primary Work, Institut Bergonie, Bordeaux, France.
authors.forename: A
authors.initials: A
authors.lastname: Fléchon
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D019468:Disease Management; D006801:Humans; D008297:Male; D018358:Neuroendocrine Tumors / Q000175:diagnosis* / Q000209:etiology / Q000628:therapy*; D063868:Patient Outcome Assessment; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000209:etiology / Q000628:therapy*
chemical_list: D014408:Biomarkers, Tumor