Bronchial Carcinoids: From Molecular Background to Treatment Approach.

Abstract

Simple SummaryBronchial carcinoids (BCs) are uncommon and usually slow growing neuroendocrine epithelial malignancies that represent less than 2% of all lung cancers. Differences in the extent of molecular alterations between neuroendocrine carcinomas and BCs may underline the differences in the aggressiveness of these lesions. Moreover, although atypical BCs and typical BCs have similar set of mutations, some differential molecular and genetic alterations have been described between these two entities. A better understanding of the genetic and molecular background of BCs would allow a better selection of medical treatments in these patients. Regarding treatment, most BCs can be cured by surgery; however, inoperable tumors are mostly insensitive to chemotherapy and radiotherapy. In advanced BCs, the only drug that has a positive phase III clinical trial in BCs is everolimus. Somatostatin analogues constitute the gold standard for symptomatic relief. Peptide receptor radionuclide therapy has been associated with longer progression free. The efficacy of other treatments such as antiangiogenic agents and immunotherapy is still not established.A better understanding of the genetic and molecular background of bronchial carcinoids (BCs) would allow a better estimation of the risk of disease progression and the personalization of treatment in cases of advanced disease. Molecular studies confirmed that lungs neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) are different entities; thus, no progression of NET to NEC is expected. In BCs, MEN1 gene mutations and deletions and decreased gene expression have been associated with a poor prognosis. ATRX mutation has also been linked to a shorter disease-specific survival. In terms of therapeutic targets, PI3K/AKT/mTOR pathway mutations have been described in 13% of typical carcinoids (TCs) and 39% of atypical carcinoids (ACs), representing a targetable mutation with kinase inhibitors. Regarding treatment, surgical resection is usually curative in localized BCs and adjuvant treatment is not routinely recommended. Multiple options for systemic therapy exist for patients with advanced BCs, although limited by a heterogeneity in the scientific evidence behind their use recommendation. These options include somatostatin analogues, everolimus, peptide receptor radionuclide therapy, chemotherapy, radiotherapy, antiangiogenic agents, and immunotherapy. In this article, we provide a comprehensive review about the molecular and genetic background of BCs, and about the treatment of local and metastatic disease, as well as the main paraneoplastic syndromes that have been associated with this tumor.