Current diagnostics and therapy of gastroenteropancreatic neuroendocrine tumors (GEP-NET)

Context. Neuroendocrine tumors can arise in almost all tissues and organs of the body. This systematic review focuses on neuroendocrine neoplasias of the digestive system and the pancreas, the so-called gastroenteropancreatic neuroendocrine tumors (GEP-NET). Objective. The aim of this study was an evidence-based systematic review of the current status of the diagnostics and therapy of GEP-NETs. Material and methods. A systematic literature search was performed in Pubmed, MEDLINE, current guidelines and by manual searching. Relevant publications from the last 5 years were analyzed and results were summarized in a structured review. Results. A novel grading and staging system for tumors of the digestive system was introduced by the World Health Organization (WHO) in 2010. By this system NETs are classified on the basis of the histologically deter-mined proliferation rate as NETs (grades III) and neuroendocrine carcinomas (grade III). Results from epidemiological studies indicate an increasing prevalence and incidence of GEP-NETs worldwide over recent decades; however, this may be a result of improved detection and diagnostic methods. A substantial improvement of detection has been achieved by the introduction of molecular imaging by positron emission tomography-computed tomography (PET-CT) imaging. Surgical removal and treatment with somatostatin analogues is the mainstay of therapeutic strategies for these tumors. Radiotherapy including stereotactic high-precision radiation can be used for local treatment of metastases. While there is currently no clear evidence, novel chemotherapeutic agents, small molecules, and biologicals can improve the prognosis of patients with GEP-NETs in the future. Conclusions. The WHO grading and staging system of 2010 supports the establishment of an individualized therapeutic strategy for each patient based on the tumor stage. Novel molecular tracers can be used in PET-CT imaging to detect even small tumors better and with a higher sensitivity. Surgical resection and medical treatment with somatostatin analogues represent central treatment strategies of GEP-NETs. Peptide receptor radionuclide therapy (PRRT) and novel pharmaceutical approaches, such as tyrosine kinase inhibitors and everolimus represent further therapeutic options. Treatment of neuroendocrine carcinomas (G3) with cisplatin and etoposide is still a valid treatment approach.