Neuroendocrine system

Rare cancer of the neuroendocrine system

Domain 4



Neuroendocrine Tumors (NETs) are rare tumors but their incidence and prevalence is increasing and given patients’ often long survival, the prevalence of NETs is now known to be significantly higher than gastric, pancreatic, oesophageal or hepatobiliary adenocarcinomas

The management of NETs has been organized in reference centers since over 10 years, enabling accurate diagnosis, customized management, and development of clinical research programs leading to approval of targeted therapies.


NETs can arise from any organ of the body but most commonly the small bowel, pancreas and lung.


The biological behavior of NETs varies widely and is influenced by tumor grade based on Ki67 proliferation index thus Grade 1 <3%; Grade 2, 3-20%; and grade 3, >20% but divided into well differentiated NET v poorly differentiated NE cancer (NEC), Additionally  stage and primary site of origin also affect biological behavior and choice of management.


In NET, an expert multidisciplinary meeting to guide management decisions remains paramount.

The most sensitive imaging modality is based on the gallium-68 DOTA Somatostatin Analog PET imaging.

Treatment options for metastatic NET are broad and encompass therapies for hormonal control, surgery, liver directed therapies and systemic therapy. Somatostatin analogs (SSA) are first line for hormonal syndrome control. The anti-tumor therapies have advanced with the randomized studies in the last decade. SSA are usually first line therapy for tumor control in well differentiated NE. Molecular targeted agents e.g. everolimus or sunitinib and often used second line for slowly progressive pancreatic NET. Everolimus has also been licensed for use in intestinal NET and bronchial NE. The greatest advance in the last decade has been Peptide Receptor Radionuclide Therapy (PRRT) with Lutetium 177 DOTATATE recently licensed for use in gastroenteropancreatic NETs. Chemotherapy for large volume or more rapidly progressive NET includes temozolomide regimen for pancreatic NET and for progressive poorly differentiated NET/NEC platinum regimens are often used.

Novel treatment options must be explored, especially in the higher grade cohort. While prognostic factors are well-defined in the literature, new biomarkers and predictors of treatment response are greatly needed and will be expanded in the future by the molecular profiling of these tumors. Finally, the often long patient survival and multiple sequential therapies with potential adverse effects, places strong emphasis on the importance of quality of life and survivorship in this patient population which must be prioritised in the future and highlights the crucial role patient support and advocacy groups have in the holistic management of these patients.

Improving the access to reference centers for patients with NETs is therefore essential since these rare tumors have multiple therapeutic options and long life expectancy when treated according to clinical practice guidelines.

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