Focal Neuroendocrine Differentiation of Conventional Prostate Adenocarcinoma as a Prognostic Factor after Radical Prostatectomy: A Systematic Review and Meta-Analysis
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Department of Urology, Medical University of Vienna, A-1090 Vienna, Austria
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Department of Urology, Shariati Hospital, Tehran University of Medical Sciences, Teheran 1411713135, Iran
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Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
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Department of Urology, Jikei University School of Medicine, Tokyo 105-8461, Japan
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Department of Urology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
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Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman 11942, Jordan
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Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, QC H3h 1s8, Canada
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Centre de recherche du Centre Hospitalier de l’Université de Montréal (CR-CHUM), Institut du Cancer de Montréal, Montréal, QC H3h 1s8, Canada
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Institute for Urology and Reproductive Health, Sechenov University, Moscow 119991, Russia
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Department of Urology, Medical University Graz, A-8036 Graz, Austria
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Department of Urology, Weill Cornell Medical College, New York, NY 10011, USA
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Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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Karl Landsteiner Institute of Urology and Andrology, A-1090 Vienna, Austria
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(6), 1374; https://doi.org/10.3390/ijms20061374
Received: 2 February 2019 / Revised: 11 March 2019 / Accepted: 13 March 2019 / Published: 19 March 2019
(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Biomarkers in Prostate Cancer 2019)
The biologic and prognostic value of focal neuroendocrine differentiation (NED) in conventional prostate adenocarcinoma (PC) patients who undergo radical prostatectomy (RP) remains controversial. In this systematic review and meta-analysis, we assessed the association of focal NED in conventional PC with oncological outcomes after RP. A literature search using PubMed, Scopus, Web of Science, and Cochrane Library was conducted on December 2018 to find relevant studies according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. We used a fixed-effect model to analyze the impact of focal NED in RP specimen on progression-free survival defined by biochemical recurrence (BCR). A total of 16 studies with the outcomes of disease progression and survival were eligible. No patient in these studies received androgen deprivation therapy prior to RP. Eleven studies found no significant correlation between focal NED and outcomes of interest, while five studies reported a significant association of focal NED assessed by immunohistochemical chromogranin A or serotonin staining with BCR or survival. Focal NED was associated with higher BCR rates after RP with a pooled HR of 1.39 (95% CI 1.07‒1.81) in five studies. No heterogeneity was reported in this analysis (I2 = 21.7%, p = 0.276). In conclusion, focal NED in conventional PC is associated with worse prognosis after RP. Its presence should be reported in pathologic reports and its true clinical impact should be assessed in well-designed prospective controlled studies.