Clinical/pathological features and survival outcomes of extra-pulmonary neuroendocrine carcinomas: A retrospective single-center series

Poorly differentiated neuroendocrine carcinomas (NECs) are rare malignancies with a dismal prognosis, few therapeutic options, and a lack of predictive factors. We describe a large series of extra-pulmonary (EP) NEC patients from a neuroendocrine neoplasm (NEN) referral center, aiming to improve the clinical management of these diseases. Medical records of patients with histological diagnosis of pure histology EP-NEC, discussed at the NEN-dedicated multidisciplinary team (MDT) between October 2018 and August 2022, were included. Demographic features, tumor characteristics, molecular profile, treatments, and responses to treatments were collected. Among 1594 NEN diagnoses discussed at the MDT during the study period, 377 were NECs; the final population consisted of 173 patients, mostly presenting with advanced disease and often with a gastroenteropancreatic tract primary tumor. Molecular profiling was available for 52 patients (30%). The most frequent alterations occurred in TP53 and KRAS. One of 25 patients tested for microsatellite instability was confirmed MSI-h; one of 52 patients tested had a high tumor mutational burden (TMB = 19). Median overall survival (OS) was 15.4 months (95% confidence interval [CI]: 13.2–18.5). Most patients with advanced disease received a first-line chemotherapy (136/153 [88.9%]), often platinum plus etoposide (111/136 patients [82%]). The overall response rate (ORR) to first-line was 40%. Median progression-free survival (PFS) was 5.7 months (95% CI: 4.4–6.4). Forty-two percent and 18% of patients received second- and third-line therapy, respectively. No significant difference was seen when stratifying OS and PFS by Ki-67 groups and tumor cell morphology, whereas performance status and presence of metastases were significantly related to OS. In this single-center retrospective large series of EP-NECs, almost half of the patients showed a tumor response to first-line chemotherapy. No relevant correlation was found with primary site, tumor cell morphology, or Ki-67. The proportion of patients receiving subsequent lines, along with the mOS, confirms the aggressiveness of this disease. Molecular profiling was performed only fragmentarily, with limited practical applicability. Efforts shall be made in the future to implement these investigations.