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, clinical-grade evidence for treatment options in second-line and beyond is very limited. The aim of this study was to analyze the treatment outcomes of NEPC patients.
Retrospective analysis of all patients 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.
Of 43 identified patients 18 (41.9 %) had a prior diagnosis of prostatic adenocarcinoma only, 19 (44.2 %) had a mixed differentiation at NEPC diagnosis, 29 (67.4 %) developed visceral metastases, 5 (15.4 %) showed paraneoplastic syndromes. Overall survival from diagnosis of any prostatic malignancy was 69.2 months, from NEPC diagnosis 15.5 months. 31 patients received palliative first line chemotherapy, mostly PE. Overall response rate (ORR) for PE was 50 %, median progression-free survival (PFS) was 6.6 months. 15 patients received second line therapy, mostly with poor response rates. Regimens with notable activity were topotecan (1 PR, 3 PD), enzalutamide (1 SD), abiraterone (1 SD), FOLFIRI (2 SD), and ipilimumab+nivolumab (1 PR). A single patient with prostatic carcinoid was sequentially treated with octreotide, peptide receptor radionuclide therapy (PRRT) and everolimus and survived for more than 9 years.
Visceral metastases and paraneoplastic syndromes are frequent in NEPC. EP in first-line shows notable ORR, however limited PFS. For patients with progression after first line therapy, topotecan, FOLFIRI, enzalutamide, abiraterone and immune checkpoint blockade are possible treatment options. Prostatic carcinoids can be treated in analogy to well differentiated NETs of the gastrointestinal tract.
Clinical trial identification
The trial was approved by the institutional research ethics committee (approval S-428/2014).
Legal entity responsible for the study
National Center for Tumor Diseases, University Hospital Heidelberg.
Has not received any funding.
All authors have declared no conflicts of interest.