Large Cell Neuroendocrine Carcinoma of the Prostate: A Systematic Review and Pooled Analysis

Background: Large cell neuroendocrine carcinoma (LCNEC) of the prostate is an extremely rare entity, and the clinicopathological course, potential effective treatment, and prognosis are yet to be elucidated.

Materials and methods: A systematic search in Pubmed, Embase, and Ovid from inception to January 2019 was conducted. We reviewed each individual case of prostatic LCNEC and summarized specific features and outcomes for this rare pathologic entity.

Results: Thirteen studies with a total of 20 patients (mean age: 70.3, range 43-87) were included in our review. Seventeen patients harbored primary LCNEC of the prostate, of which 9 patients were diagnosed with de novo carcinoma, and 8 patients were with a history of prostatic adenocarcinoma treated with hormonal therapy (mean duration: 2.9 years, range 2-5). The other 3 patients were diagnosed with metastatic LCNEC originating from lung (2 cases) and bladder (1 case). All patients met the diagnostic criteria of the typical morphological features as well as immunohistochemical staining results. Nearly all primary de novo LCNEC of the prostate were at a late stage at initial diagnosis. The pattern of distant metastasis resembled that of prostatic adenocarcinoma with the most common sites as bone spread (8/16, 50%). Most patients received systematic chemotherapy after diagnosis; however, the prognosis remained poor and patients deteriorated rapidly but with exception. Three reported cases in the context of de novo LCNEC admixed with prostatic adenocarcinoma kept sustained response to androgen deprivation therapy (ADT) and achieved obviously better survival outcomes compared with other patients.

Conclusions: LCNEC of the prostate is a rare entity that mostly occurs after long-standing hormonal therapy of prostatic adenocarcinoma. The prognosis was universally poor irrespective of the systematic chemotherapy. However, patients of de novo tumor mixed with prostatic adenocarcinoma may respond to ADT and harbor a better outcome than those of pure de novo or post-ADT LCNEC of the prostate.