The role of peptide receptor radionuclide therapy in advanced/metastatic thoracic neuroendocrine tumors

Bronchopulmonary (BP) neuroendocrine tumors (NETs) comprise a spectrum of tumors that develop from respiratory neuroendocrine cells and represent ~20% of all lung neoplasia and ~30% of all NETs. The only curative treatment is surgical resection. For well-differentiated forms (typical and atypical carcinoids), medical therapy ranges from bioactive agents (e.g., somatostatin analogs), to biotherapy (e.g., everolimus), standard chemotherapy and peptide receptor radionuclide therapy (PRRT). PRRT with radiolabeled somatostatin analogs is an innovative treatment for inoperable or metastasized, well/moderately differentiated, NET. Initially developed for gastroenteropancreatic tumors, it is also used in BP-NET because these tumors express the target receptor. Two decades of clinical trials with either 90 Y-octreotide or 177 Lu-octreotate, have demonstrated the efficacy of PRRT, as measured by tumor response, symptom relief and quality of life (QoL) improvement. PRRT with 90 Y- and 177 Lu-peptides is generally well-tolerated and adverse events (kidney and bone marrow) are modest. The paper illustrates the history, technique and results of this treatment in the few dedicated studies and the many BP NET cases embedded within larger NET series. The limitations of the present body of information are addressed, and the future perspectives, in terms of prospective studies required to define the position of PRRT in the therapeutic algorithm of BP-NETs and the need for predictive molecular biomarkers to guide future studies, are discussed.