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Clinical characteristics, treatment outcomes and potential novel therapeutic options for patients with neuroendocrine carcinoma of the prostate.

ABSTRACT: Background:Neuroendocrine carcinomas of the prostate (NEPCs) are rare tumors with poor prognosis. While platinum and etoposide-based chemotherapy regimens (PE) are commonly applied in first-line for advanced disease, evidence for second-line therapy and beyond is very limited. Methods:Retrospective analysis of all patients with NEPCs including mixed differentiation with adenocarcinoma component and well differentiated neuroendocrine tumors (NETs, carcinoids) at two high-volume oncological centers between 12/2000 and 11/2017. Results:Of 46 identified patients 39.1 % had a prior diagnosis of prostatic adenocarcinoma only, 43.5 % had a mixed differentiation at NEPC diagnosis, 67.4 % developed visceral metastases, 10.9 % showed paraneoplastic syndromes. Overall survival (OS) from NEPC diagnosis was 15.5 months, and significantly shorter in patients with a prior prostatic adenocarcinoma (5.4 vs. 32.7 months, p=0.005). 34 patients received palliative first-line systemic therapy with a median progression-free survival (PFS) of 6.6 months, mostly PE. Overall response rate (ORR) for PE was 48.1 %. 19 patients received second-line therapy, mostly with poor responses. Active regimens were topotecan (1 PR, 3 PD), enzalutamide (1 SD), abiraterone (1 SD), FOLFIRI (1 SD), and ipilimumab+nivolumab (1 PR). One patient with prostatic carcinoid was sequentially treated with octreotide, peptide receptor radionuclide therapy and everolimus, and survived for over 9 years. Conclusions:EP in first-line shows notable ORR, however limited PFS. For second-line therapy, topotecan, FOLFIRI, enzalutamide, abiraterone and immune checkpoint blockade are treatment options. Prostatic carcinoids can be treated in analogy to well differentiated gastrointestinal NETs.

SUBMITTER: Apostolidis L

PROVIDER: S-EPMC6343754 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Clinical characteristics, treatment outcomes and potential novel therapeutic options for patients with neuroendocrine carcinoma of the prostate.

Apostolidis Leonidas L Nientiedt Cathleen C Winkler Eva Caroline EC Berger Anne Katrin AK Kratochwil Clemens C Kaiser Annette A Becker Anne-Sophie AS Jäger Dirk D Hohenfellner Markus M Hüttenbrink Clemens C Pahernik Sascha S Distler Florian A FA Grüllich Carsten C

Oncotarget 20190101 1

<h4>Background</h4>Neuroendocrine carcinomas of the prostate (NEPCs) are rare tumors with poor prognosis. While platinum and etoposide-based chemotherapy regimens (PE) are commonly applied in first-line for advanced disease, evidence for second-line therapy and beyond is very limited.<h4>Methods</h4>Retrospective analysis of all patients with NEPCs including mixed differentiation with adenocarcinoma component and well differentiated neuroendocrine tumors (NETs, carcinoids) at two high-volume onc ...[more]

PMID: 30713600

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Project description:Poorly differentiated gastroenteropancreatic neuroendocrine carcinomas (GEPNECs) are a rare neoplasm with a bleak prognosis. Currently there are little prospective data available for optimal treatment. This review discusses the current available regimens and the future direction for the treatment of GEPNECs. Treatment plans for GEPNECs are often adapted from those devised for small cell lung cancer; however, differences in these malignancies exist, and GEPNECs require their own treatment paradigms. As such, current first-line treatment for GEPNECs is platinum-based chemotherapy with etoposide. Studies show that response rate and overall survival remain comparable between cisplatin and carboplatin versus etoposide and irinotecan; however, prognosis remains poor, and more efficacious therapy is needed to treat this malignancy. Additional first-line and second-line treatment options beyond platinum-based chemotherapy have also been investigated and may offer further treatment options, but again with suboptimal outcomes. Recent U.S. Food and Drug Administration approval of peptide receptor radionuclide therapy in low- and intermediate-grade neuroendocrine tumors may open the door for further research in its usefulness in GEPNECs. Additionally, the availability of checkpoint inhibitors lends promise to the treatment of GEPNECs. This review highlights the lack of large, prospective studies that focus on the treatment of GEPNECs. There is a need for randomized control trials to elucidate optimal treatment regimens specific to this malignancy. IMPLICATIONS FOR PRACTICE: There are limited data available for the treatment of poorly differentiated gastroenteropancreatic neuroendocrine carcinomas (GEPNECs) because of the rarity of this malignancy. Much of the treatment regimens used in practice today come from research in small cell lung cancer. Given the poor prognosis of GEPNECs, it is necessary to have treatment paradigms specific to this malignancy. The aim of this literature review is to summarize the available first- and second-line GEPNEC therapy, outline future treatments, and highlight the vast gap in the literature.

Project description:Introduction: Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer, exhibiting rapid progression and is unresponsive to hormone therapy. Reliable prognostic assays and more effective treatments are critically required. However, the research of NEPC has been hampered by a lack of clinically relevant in vivo models. Recently, we successfully developed a first-in-field patient tissue-derived xenograft model of complete neuroendocrine transdifferentiation from prostate adenocarcinoma. By comparing gene expression profiles of the parental adenocarcinoma line (LTL331) and the NEPC subline (LTL331R), we identified DEK, a gene not previously reported in prostate cancer, as a potential biomarker and target for NEPC. Methods: DEK protein expression in patient tissue-derived xenograft models and clinical samples was assessed by immunohistochemistry. The function of DEK was determined by siRNA-induced reduction of DEK expression in PC-3 cells, a cell line with NEPC characteristics, followed by functional assays and gene expression profiling analysis. Results: Elevated DEK protein expression was observed in all clinical NEPC cases, which is distinct from their benign counterparts (0%), hormonal naïve prostate cancer (2.45%) and castration resistant prostate cancer (29.55%). Increased DEK expression is an independent clinical risk factor and is associated with shorter disease free survival in hormonal naïve prostate cancer patients. Reduction of DEK expression in PC-3 cells led to a marked reduction in cell proliferation, cell migration and invasion. Conclusions: The results suggest that DEK may play an important role in the progression of prostate cancer, especially NEPC and provide a potential biomarker to aid risk stratification of prostate cancer and a novel therapeutic target for treating NEPC. The function of DEK was determined by siRNA-induced reduction of DEK expression in PC-3 cells, a cell line with NEPC characteristics, followed by functional assays and gene expression profiling analysis.

Project description:BackgroundDocetaxel (DOC) and abiraterone (ABI) in the upfront setting have separately improved clinical outcomes for metastatic hormone-sensitive prostate cancer (mHSPC), but there are no studies comparing drug efficacies or the influence of racial disparities.Materials and methodsWe performed a retrospective multicenter review from Winship Cancer Institute at Emory University and Georgia Cancer Center for Excellence at Grady Memorial Hospital (2014-2020) for patients with mHSPC treated with either upfront DOC or ABI. Outcomes evaluated were overall survival (OS), progression-free survival (PFS), and prostate-specific antigen complete response (PSA CR).ResultsA total of 168 patients were included, consisting of 92 (54.8%) Black patients and 76 (45.2%) non-Black patients (69 White and 7 Asian or Hispanic). Ninety-four (56%) received DOC and 74 (44%) received ABI. Median follow-up time was 22.8 months with data last reviewed June 2020. For OS, there was no significant difference between ABI versus DOC and Black versus non-Black patients. For PFS, DOC was associated with hazard ratio (HR) 1.7 compared with ABI for all patients based on univariate association and HR 2.27 compared with ABI for Black patients on multivariable analysis. For PSA CR, Black patients were less likely to have a CR (odds ratio [OR] = 0.27).ConclusionABI and DOC have similar OS with a trend toward better PFS for ABI in a cohort composed of 54% Black patients. Racial disparities were observed as prolonged PFS for Black patients treated with ABI, more so compared with all patients, and less PSA CR for Black patients. A prospective trial comparing available upfront therapies in a diverse racial population is needed to help guide clinical decision-making in the era of novel treatment options.Implications for practiceOverall survival is similar for abiraterone and docetaxel when used as upfront therapy in metastatic hormone-sensitive prostate cancer in a cohort composed of 54% Black patients. There is a trend towards improved progression-free survival for abiraterone in all patients and Black patients. Non-Black patients were more likely to achieve prostate-specific antigen (PSA) complete response regardless of upfront therapy.

Dataset Information

Clinical characteristics, treatment outcomes and potential novel therapeutic options for patients with neuroendocrine carcinoma of the prostate.

Publications

Clinical characteristics, treatment outcomes and potential novel therapeutic options for patients with neuroendocrine carcinoma of the prostate.

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