Abstract
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.
Highlights
Prostate cancer (PC) is the most common solid cancer and the second most common cause of cancer-related death in men [1]
This systematic review and meta-analysis aimed to elucidate the prognostic value of focal neuroendocrine differentiation (NED) in conventional PC on disease progression and survival after radical prostatectomy (RP)
We found that PC patients with focal NED in their RP specimen have an increased probability of biochemical recurrence (BCR) compared to patients without focal NED
Summary
Prostate cancer (PC) is the most common solid cancer and the second most common cause of cancer-related death in men [1]. Over 90% of newly diagnosed PCs in developed countries are clinically localized to the origin. The standard treatment for these tumors is either active surveillance or local therapy with radical prostatectomy (RP) or radiation therapy. While these therapies result in durable local and distant disease control [2,3]. Increasing attention has been given to neuroendocrine differentiation (NED) of PC recognizing its potential diagnostic, prognostic, and therapeutic utility [8]. Neuroendocrine cells are androgen-independent because of their negative androgen receptor expression [8]. NED is an important factor influencing the development of PC toward an androgen-independent, lethal phenotype
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