A systematic review of primary large cell neuroendocrine carcinoma of the prostate

Abstract

BackgroundLarge cell neuroendocrine carcinoma (LCNEC) is a rare subtype of prostate cancer. The pathogenesis, clinical manifestation, treatment options, and prognosis are uncertain and underreported.Materials and methodsA systematic search was conducted in April 2022 through PubMed, Embase, and Cochrane. We reviewed cases of LCNEC developed either from de novo or transformation from prostate adenocarcinoma and summarized the relevant pathophysiological course, treatment options, and outcomes.ResultsA total of 25 patients with a mean age of 70.4 (range 43 87 years old) from 18 studies were included in this review. 13 patients were diagnosed with de novo LCNEC of the prostate. 12 patients were from the transformation of adenocarcinoma post-hormonal therapy treatment. Upon initial diagnosis, patients diagnosed with de novo prostatic LCNEC had a mean serum PSA value of 24.6 ng/ml (range: 0.09-170 ng/ml, median 5.5 ng/ml), while transformation cases were significantly lower at 3.3 ng/ml (range: 0-9.3 ng/ml, median 0.05 ng/ml). The pattern of metastasis closely resembles prostate adenocarcinoma. Six out of twenty-three cases displayed brain metastasis matching the correlation between neuroendocrine tumors and brain metastasis. Three notable paraneoplastic syndromes included Cushings syndrome, dermatomyositis, and polycythemia. Most patients with advanced metastatic disease received conventional platinum-based chemotherapy with a mean survival of 5 months. There was one exception in the transformation cohort with a somatic BRCA2 mutation who was treated with a combination of M6620 and platinum-based chemotherapy with an impressive PFS of 20 months. Patients with pure LCNEC phenotype have worse survival outcomes when compared to those with mixed LCNEC and adenocarcinoma phenotypes. It is unclear whether there is a survival benefit to administering ADT in pure pathologies.ConclusionLCNEC of the prostate is a rare disease that can occur de novo or transformation from prostatic adenocarcinoma. Most patients present at an advanced stage with poor prognosis and are treated with conventional chemotherapy regimens. Patients who had better outcomes were those who were diagnosed at an early stage and received treatment with surgery or radiation and androgen deprivation therapy (ADT). There was one case with an exceptional outcome that included a treatment regimen of M6620 and chemotherapy.

Systemic metastases in large cell neuroendocrine prostate cancer: a rare case report and literature review

“…After 5 cycles, imaging revealed improvement of the sclerotic lesions, and no new metastatic lesions were detected, with the PSA value measuring less than 0.01ng/mL. It shows that docetaxel and prednisone may have efficacy in the treatment of LCNEPC ( 15 ). In our case, the patient was not treated with docetaxel, making it impossible to know whether the patient would have had a better outcome and longer survival.…”

“…The average time from the first diagnosis of prostate cancer to the diagnosis of LCNEPC was 4.7 years (range 2–9 years). Among the patients diagnosed with LCNEPC, chemotherapy was administered to 7 individuals, and the final outcome in 11 patients was death or loss to follow-up ( 15 ). Currently, only one patient, who harbored a somatic BRCA2 mutation, survived after receiving treatment with the Rad3-related protein (ATR) Inhibitor (M6620) in conjunction with gemcitabine, cisplatin, and etoposide, achieving a progression-free survival (PFS) of 20 months ( 16 ).…”

“…Based on the available literature, a total of 12 cases of primary LCNEC of the prostate were reported with an average overall survival of 21.5 months(range 7–54 months) ( 15 ). Patients with a diagnosis of pure LCNEPC who received a chemotherapy regimen of etoposide + cisplatin after diagnosis still had an extremely poor prognosis, with a mean survival of 7.3 months ( 5 , 17 ).…”