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

// Leonidas Apostolidis 1 , Cathleen Nientiedt 1 , Eva Caroline Winkler 1 , Anne Katrin Berger 1 , Clemens Kratochwil 2 , Annette Kaiser 3 , Anne-Sophie Becker 3 , Dirk Jäger 1 , Markus Hohenfellner 4 , Clemens Hüttenbrink 5 , Sascha Pahernik 5 , Florian A. Distler 5, * and Carsten Grüllich 1, * 1 Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany 2 Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany 3 Institute of Pathology, Klinikum Nuremberg, Paracelsus Medical University, Nuremberg, Germany 4 Department of Urology, University Hospital Heidelberg, Heidelberg, Germany 5 Department of Urology, Klinikum Nuremberg, Paracelsus Medical University, Nuremberg, Germany * These authors have contributed equally to this work Correspondence to: Leonidas Apostolidis, email: leonidas.apostolidis@med.uni-heidelberg.de Keywords: neuroendocrine carcinoma; neuroendocrine tumor; carcinoid; prostate; chemotherapy Received: September 19, 2018      Accepted: December 10, 2018      Published: January 01, 2019 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.