Understanding Neuroendocrine Tumors (NETs): Symptoms, diagnosis, and advanced treatment options

Neuroendocrine tumors (NETs) arise from special cells in our body, which regulate various functions either by secretion of hormones or via neurotransmitters. These tumors can arise practically in every organ, but are more common in gastro-intestinal tract, lung, thyroid, adrenals. These tumors are unique in many ways. Because they arise from Neurosecretory cells, many of these tumors manifest due to oversecretion of certain hormones giving rise to clinical syndromes. For example a small tumor in the duodenum called a ‘Gastrinoma’ can secrete excess amounts of Gastrin that causes ‘acidity’. A small tumor in Pancreas called ‘Insulinoma’ can cause hypersecretion of Insulin leading to low blood sugar, fainting spells. Tumors in the intestines secreting various peptides can cause chronic diarrhoea, flushing, low blood pressure (Carcinoid syndrome). Some tumors secrete high Adrenalin and Noradrenalin and cause very high blood pressure. Because of this wide range of rather common medical presentations, these patients often get treated in a non specific way for years, running from doctor to doctor seeking a solution for their complaints. They may land up at the clinic of a gastro-enterologists, endocrine specialist, general physician, cardiologist, or neurologist. Good clinical acumen is needed to recognize and decipher the symptomatology and then seek appropriate tests to be able to diagnose these tumors.
The other unique factor about NETs is that even though the primary tumor may be very small, they can still spread / metastasize to other organs in the body. In fact, in larger number of cases, these tumors lose their ability to secrete hormones, and are ‘non-secretory’. They present later in the stage of disease quite silently, as multiple metastatic tumors in liver, bones or other parts of the body. At this stage the aggressiveness and prognosis of these tumors depends upon their pathological grade. While the Grade 1 and 2 NETs are relatively indolent, grow quite slowly and can be managed for years, the high grade 3 tumors or NEC (Neuroendocrine Carcinomas) are more aggressive with a worse prognosis.


In the past, treatment of NET was done similar to conventional cancers arising from the respective organs – but response was poor. Now, in light of new research, that these tumors are a separate entity, newer Targeted therapies are used to treat these tumors. When initially detected and small, these tumors can be treated by endoscopic resection or by surgery. Disease which has spread need various targeted treatments. Another unique factor about these tumors – they overexpress certain receptors called Somatostatin Receptors (SSTR). Low grade tumors can be controlled for long periods with monthly injections of Somatostatin analogues. Upon disease progression, there is a significant role of SSTR directed Radionuclide Targeted Therapy ie PRRT using Lu177-DOTATATE which is given by Nuclear Medicine specialists. A variety of drugs like Everolimus, platinum based chemotherapies are used for the higher grade tumors. Liver directed therapies through Interventional Radiology are available to treat large metastatic tumors in the liver.
The incidence of these tumors is rising in the past decade - mostly attributing to the significant advances in diagnostics including IHC tests on pathology and DOTATATE PET-CT scans, which leads to specific diagnosis of NET, rather than actual increase in incidence. However advances in targeted therapies has lead to improved survival and quality of life even in those with metastatic disease. The good thing is that all these treatments are now available and being used effectively in India. It has to be emphasized that this is a disease entity which needs multiple clinical specialties and effective dedicated NET teams can provide the comprehensive management needed for these patents.

Authored by: Dr Vijay Haribhakti, Chair, Oncology, Surgical Oncology- Head & Neck, Breast and General, Sir H.N. Reliance Foundation Hospital and Dr Karuna Luthra, Director, Nuclear Medicine, Sir H.N. Reliance Foundation Hospital

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