Clinical investigation of neuroendocrine differentiation in prostate cancer.

Abstract

138 Background: Neuroendocrine prostate cancer (NEPC) is a lethal disease subset with median overall survival of less than 1 year from time of detection. The treatment strategy against NEPC is not yet established and some clinical trials are ongoing now. Recently, clinical trial (RADIIANT4) showed that treatment with everolimus was associated with significant improvement in survival in patients with progressive lung or gastrointestinal neuroendocrine tumors. In this study we evaluated the neuroendocrine differentiation of prostate cancer and we tried to introduce everolimus against pathologically proven NEPC and investigated the clinical outcomes of this agent. Methods: Total of 193 prostate cancer cases were included in this study. We tested serum neuroendocrine markers, including (NSE and pro-GRP). And we evaluated positive rate of these markers. Eleven cases were pathologically proven neuroendocrine prostate cancer (NEPC) in this cohort. Seven out of eleven NEPC cases were introduced everolimus 10mg daily. We investigated the change of serum neuroendocrine markers (NSE and pro-GRP), radiologic examination and survival. Results: The positive rate of serum neuroendocrine markers (at least one of the markers increasing above normal limit) were 23.5% in hormone sensitive prostate cancer (HSPC), 59.5% in castration resistant prostate cancer (CRPC), and 100% in neuroendocrine prostate cancer (NEPC). There were significant differences in each other (HSPC vs. CRPC: p=0.0001, CRPC vs. NEPC: p=0.0109). We introduced everolimus in seven cases out of eleven NEPC cases. The median follow up period was 18 months. Neuroendocrine markers decreased in five of seven (71.4%) cases after introduction of everolimus. Median decreasing rate were 67.1% in NSE and 65.5% in pro GRP. 24M progression free survival rate was 57.1% and 24M overall survival rate was 57.1%. Conclusions: There is a possibility that the incidence of NEPC is higher than expected, and treatment against prostate adenocarcinoma accelerate neuroendocrine differentiation. Everolimus showed efficacy against NEPC. Although this study was retrospective and number of cases was limited, everolimus would be a one of the treatment options against NEPC.

Neuroendocrine Differentiation of Prostate Cancer Is Not Systematically Associated with Increased 18F-FDG Uptake

“…While the former PET/CT showed very mild to moderate tracer uptake in a few pelvic and vertebral bone lesions (maximum Standardized Uptake Value (SUVmax): 2.5 vs. 4 at baseline), the latter showed a widespread, intensely Dotatoc-avid skeletal, pleural, and lymph nodal disease burden (SUVmax: 64 vs. 5 at baseline) (Panels ( C , D )). This result was interpreted as a progression of the NED part of the disease, not tracked by PSA kinetics in agreement with the acknowledged low-PSA secretion tendency of this kind of tumor [ 8 , 9 , 10 ]. On the one hand, the present case challenges FDG PET/CT’s acknowledged prognostic value in mCRPC patients.…”

“…This kind of NED represents a later transformation of ordinary adenocarcinoma’s cellular clones to the neuroendocrine phenotype, favored by the selective pressure of androgen-targeted therapy and allowing advanced PC to escape the androgen deprivation [ 7 ]. Its main clinical manifestations include androgen deprivation resistance, low PSA levels, the disproportion between PSA kinetics and tumor burden progression, and the eventual increase in serum neuroendocrine tumor markers [ 8 , 9 ]. On this basis, 9 days after, the patient underwent 68Ga-DOTATOC PET/CT (Panel ( B )), which detected mild tracer uptake in almost all bone lesions seen at 18F-FDG imaging and two 18F-FDG negative pleural lesions.…”

Treatment-Emergent Neuroendocrine Prostate Cancer: A Clinicopathological and Immunohistochemical Analysis of 94 Cases

“…When prostate cancer patients were clinically resistant to hormonal therapy, presented with the clinical features such as carcinoid syndrome, lower urinary tract symptoms, osteolytic bone metastases, visceral metastases as progressive metastases on imaging ( 14 ). In addition, an increase of serum neuroendocrine markers CGA and NSE, or the low level or significantly elevated level of PSA was disproportionate to tumor progression, the possibility of T-NEPC should be considered ( 15 ).…”