Clinical characteristics, treatment outcomes and potential novel therapeutic options for patients with neuroendocrine carcinoma of the prostate
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Leonidas Apostolidis1, Cathleen Nientiedt1, Eva Caroline Winkler1, Anne Katrin Berger1, Clemens Kratochwil2, Annette Kaiser3, Anne-Sophie Becker3, Dirk Jäger1, Markus Hohenfellner4, Clemens Hüttenbrink5, Sascha Pahernik5, Florian A. Distler5,* and Carsten Grüllich1,*
1Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany
2Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany
3Institute of Pathology, Klinikum Nuremberg, Paracelsus Medical University, Nuremberg, Germany
4Department of Urology, University Hospital Heidelberg, Heidelberg, Germany
5Department of Urology, Klinikum Nuremberg, Paracelsus Medical University, Nuremberg, Germany
*These authors have contributed equally to this work
Leonidas Apostolidis, email: [email protected]
Keywords: neuroendocrine carcinoma; neuroendocrine tumor; carcinoid; prostate; chemotherapy
Received: September 19, 2018 Accepted: December 10, 2018 Published: January 01, 2019
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.
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