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

Abstract

BackgroundNeuroendocrine 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.MethodsRetrospective 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.ResultsOf 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.ConclusionsEP 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.

Response Prediction of 177Lu-PSMA-617 Radioligand Therapy Using Prostate-Specific Antigen, Chromogranin A, and Lactate Dehydrogenase

“…For clinical practice, an elevated CgA and nonresponse to PSMA RLT might indicate a PSMA-negative tumor, especially in the liver. However, other variables also need to be taken in account, such as mutations in tumor suppression genes, because patients without liver metastasis and with normal CgA also had a nonresponse to PSMA treatment (30). This finding implies that in patients with a high baseline CgA, special focus should be given to liver imaging.…”

Clinicopathological characteristics and survival outcomes in neuroendocrine prostate cancer

“…In terms of treatment type, early radical resection is still the most effective method, even if there is local infiltration, should be radical resection or palliative resection. [ 21 ] As the disease is easy to metastasize, the vast majority of NEPC are already in advanced stage when they are diagnosed, so they need systemic treatment (mainly chemotherapy) which combined with radiotherapy (or surgery). Cisplatin -based combination chemotherapy is usually used to treat NEPC patients, and the effective rate of chemotherapy is about 50%.…”

Incidental finding of a small cell neuroendocrine carcinoma of the ureter

“…Small cell NET of the prostate is commoner than the large cell counterpart, is often diagnosed at a later stage and shows very poor prognosis. The mainstay of treatment is a multimodal approach using platinum-based therapy, radiation, surgery where possible and in very advanced settings watchful waiting is an option, as no known curative therapies exist 19 25 26. This can also be said of ureteric NETs; both entities are poorly understood and very understudied due to their rarity.…”