Neuroendocrine tumors (NETs) are a group of cancers that begin in the neuroendocrine cells of the body. These rare tumors can develop in tissues and organs that are part of the neuroendocrine system, such as the lungs, pancreas, gastrointestinal tract and others. While NETs can be challenging to diagnose and treat, advances in research have led to improved neuroendocrine tumor treatment options in recent years.

Diagnosing Neuroendocrine Tumors

The symptoms of NETs can vary depending on the type and location of the tumor. Common signs include abdominal pain, bowel changes, flushings, fatigue and headaches. As such, doctors may perform several tests to diagnose NETs and determine how far the cancer has spread. Initial tests often include blood tests, imaging scans like CT scans and MRIs, endoscopies, and biopsies. Blood tests can detect high levels of hormones and markers released by NET cells. Imaging tests provide details on tumor size, location and involvement of nearby organs or lymph nodes. Biopsies examine tumor tissue under a microscope to confirm a neuroendocrine tumor. Staging helps determine the extent or spread of the disease.

Staging Neuroendocrine Tumors

Neuroendocrine Tumor Treatment staging uses the TNM system to describe tumor size, involvement of nearby tissues/organs (T), affected lymph nodes (N), and distant metastases (M). Stage I and II NETs are confined to the organs they began in, while stage III tumors have spread to lymph nodes or adjacent structures. The most advanced stage IV NETs have distant metastases to other parts of the body like the liver or bones. Accurate staging is essential for tailoring the most suitable NET treatment strategy.

Treatment Options for Localized or Regional NETs

For stage I-III NETs confined to the primary site and nearby areas, treatment aims to remove the entire tumor through surgery. Depending on the cancer's location, surgery may involve the removal of the affected organ such as a pancreaticoduodenectomy. Any remaining cancer cells are then targeted using additional localized NET therapies. Some options for early-stage NETs involving a single site include:

- Radiofrequency ablation (RFA) or microwave ablation: Uses heat generated from radio waves or microwaves to destroy tumor tissue without surgery.

- Radiotherapy: Delivers high-energy rays or particles to kill cancer cells and shrink tumors. May be an option when surgery is not possible.

- Chemoembolization: An image-guided procedure that delivers chemotherapy to the tumor site via blood vessels while blocking blood flow to the area. Commonly used to treat NET liver metastases.

- Liver-directed surgery/ablation: Resection or ablation of liver tumors in conjunction with surgery on the primary site for gastrointestinal NETs with limited liver involvement. Provides the potential for a cure in selected patients.

Treatment of Metastatic or Advanced NETs

For stage IV NETs with metastases that have spread beyond the original location, a multidisciplinary care approach is required. Treatment goals often transition to improving symptoms, quality of life, and prolonging survival. Common systemic therapies include somatostatin analogs, targeted drugs, chemotherapy, and newer investigational approaches. These advanced NET treatments target cancer cells throughout the body:

- Somatostatin analogs (SSAs): Octreotide and lanreotide emulate natural somatostatin to suppress hormone secretion. They can help control symptoms from hormone-producing NETs but have limited effects on tumor growth.

- Targeted drug therapy: Drugs like sunitinib, everolimus, and pembrolizumab specifically target molecular pathways involved in NET growth and survival. They have shown activity against pancreatic and gastrointestinal NETs.

- Chemotherapy: May be used for high-grade, rapidly progressing NETs and includes platinum-based regimens, temozolomide, streptozocin, 5-FU, and dacarbazine combinations.

- Peptide receptor radionuclide therapy (PRRT): Involves attaching radioactive molecules like lutetium-177 or yttrium-90 to SSAs. This targets radiation directly to somatostatin receptor-expressing tumors, predominantly treating metastatic gastrointestinal and pancreatic NETs.

- Emerging therapies: New immunotherapies, monoclonal antibodies, angiogenesis inhibitors, PI3K/mTOR/MEK inhibitors, and gene/cell-based approaches are under active investigation for advanced NETs through clinical trials.


Neuroendocrine tumors represent a heterogeneous group of malignancies that have originated from the neuroendocrine system. While challenging to diagnose, improved awareness, diagnostic tools, and multidisciplinary care approaches have led to better understanding and management of NETs in recent years. A combination of surgery, locoregional ablative techniques, targeted medications, chemotherapy, and novel therapies form the current standard of care based on the extent and location of disease. Continued advances through dedicated clinical and translational research hold promise to further advance neuroendocrine tumor treatment outcomes in the future.

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