Therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: State-of-the-art and future perspectives

Abstract

Although gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have always been considered rare tumors, their incidence has risen over the past few decades. They represent a highly heterogeneous group of neoplasms with several prognostic factors, including disease stage, proliferative index (Ki67), and tumor differentiation. Most of these neoplasms express somatostatin receptors on the cell surface, a feature that has important implications in terms of prognosis, diagnosis, and therapy. Although International Guidelines propose algorithms aimed at guiding therapeutic strategies, GEP-NEN patients are still very different from one another, and the need for personalized treatment continues to increase. Radical surgery is always the best option when feasible; however, up to 80% of cases are metastatic upon diagnosis. Regarding medical treatments, as GEP-NENs are characterized by relatively long overall survival, multiple therapy lines are adopted during the lifetime of these patients, but the optimum sequence to be followed has never been clearly defined. Furthermore, although new molecular markers aimed at predicting the response to therapy, as well as prognostic scores, are currently being studied, their application is still far from being part of daily clinical practice. As they represent a complex disease, with therapeutic protocols that are not completely standardized, GEP-NENs require a multidisciplinary approach. This review will provide an overview of the available therapeutic options for GEP-NENs and attempts to clarify the possible approaches for the management of these patients and to discuss future perspectives in this field.

Keywords: Gastroenteropancreatic neuroendocrine neoplasms; Therapeutic strategies; Radical surgery; Medical treatments; Overview; Future perspectives

Core Tip: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have shown an increasing incidence over the past few decades. Although International Guidelines propose algorithms aimed guiding therapeutic strategies, the need for personalized treatment continues to increase. Radical resection is always the best option when feasible; however, up to 80% of cases are metastatic upon diagnosis. Several medical therapies are available for unresectable cases: Somatostatin analogs, peptide receptor radionuclide therapy, targeted drugs (primarily everolimus and sunitinib), chemotherapy and immunotherapy. This review provides an updated overview of the available therapeutic options for GEP-NENs and attempts to discuss future perspectives in this field.