NETs of the Lung

Lung carcinoids (LCs) are rare tumors, whose incidence has increased during the last decades; however, some controversies still exist on their diagnosis and management, also given the scarcity of prospective data. Surgery remains the gold standard for locoregional disease, while for advanced or progressive disease, no standard treatment or therapeutic algorithm is currently available, and multidisciplinary management is always required. Medical therapy represents the gold standard in the avanced setting, being somatostatin analogues (SSAs), everolimus, chemotherapies, peptide receptor radiotherapy (PRRT) treatments the therapeutic armamentarium. SSAs represent a viable option for both symptom and disease control, as well as PRRT with radiolabeled SSAs is an option in patients with well-differentiated low-intermediate grade neuroendocrine tumors (NETs) expressing high levels of somatostatin receptors (SSTRs). Systemic chemotherapy is reserved for those cases of locally advanced or metastatic disease, even if the standard regimen has not yet been defined. The role of targeted therapies in LCs remains still limited with the exception of the only approved drug (everolimus) in clinical practice. Regarding immunotherapy, in low-grade LCs, pembrolizumab and spartalizumab had shown preliminary promising results in terms of both safety and clinical outcome, but data from phase II study are disappointing. However, as the majority of studies exploring the efficacy of available treatments are retrieved from studies on gastroenteropancreatic NETs and/or are retrospective in nature, further studies, specifically dedicated to LCs, are needed to draw more robust conclusions, particularly to clarify the best sequence and timing of systemic drugs in the management of this subgroup of rare neoplasms.