Obesity and GEP-NEN: what's new?

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) comprise a heterogeneous group of tumors differing according to the primary lesion site, histological features, clinical status and prognosis. The etiopathogenesis of GEP-NEN is not fully elucidated, however, excessive visceral adiposity may play a role in NEN oncogenesis and pose challenges to NEN therapeutic management. The interplay between obesity and GEP-NEN is complex and the potential carcinogenic mechanisms of obesity include chronic inflammation, abnormal immune function, hormone and metabolic dysregulation. Data regarding the prognostic impact of visceral adiposity on patients' clinical and survival outcomes is still very limited and indeterminate. Molecular evidence predominantly supports the carcinogenic effects of obesity, although some studies have documented a potential protective role of excessive adiposity, i.e. the "obesity paradox" phenomenon, in NENs. Concerning therapeutic management of obesity in the setting of GEP-NENs, the current strategies to be considered include first-line nutritional and lifestyle intervention, followed by pharmacological and surgical treatment. This review aims to explore the intricate relationship between obesity and GEP-NENs, the potential impact on NEN outcomes, the current treatment approaches and future perspectives of the therapeutic landscape of individuals affected by GEP-NEN and obesity.