Neuroendocrine Tumors - Early Signs, Risk Factors, Diagnosis, and Treatment Explained

Overview: What Are Neuroendocrine Tumors?

Neuroendocrine tumors (NETs) are a group of uncommon cancers that start in specialized cells called neuroendocrine cells. These cells act like a mix between nerve cells and hormone-producing (endocrine) cells. They are found throughout the body — especially in the lungs, pancreas, and digestive tract. Because of their dual role, tumors that develop in these cells can sometimes make excess hormones, leading to unusual symptoms.

NETs are considered rare, accounting for less than 0.5% of all cancers. However, awareness and diagnosis are increasing as doctors use more advanced imaging and blood tests. Early detection matters because NETs can grow silently for years. When found at an early stage, treatment is often more effective, and survival rates improve significantly.

What Are the Types of Neuroendocrine Tumors?

Doctors classify NETs based on where they start and how they behave. The main subtypes include:

• Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs): Found in the pancreas, stomach, small intestine, rectum, and appendix.
• Lung Neuroendocrine Tumors: These include typical carcinoid tumors and atypical carcinoid tumors.
• Pheochromocytoma and Paraganglioma: Tumors that develop in the adrenal glands or near nerve clusters.
• Merkel Cell Carcinoma: A rare but aggressive skin cancer.
• Functional NETs: Tumors that release hormones and cause specific symptoms (such as insulinomas or gastrinomas).
• Nonfunctional NETs: Tumors that don’t release hormones but can still grow and spread.

What Are the Causes of Neuroendocrine Tumors?

The exact cause of neuroendocrine tumors is not always clear. Like many cancers, they result from genetic mutations in the neuroendocrine cells (which have traits of both nerve and hormone-producing cells) that make the cells grow uncontrollably. Some mutations are inherited, while others develop over time due to environmental or unknown triggers.

What Are the Risk Factors of Neuroendocrine Tumors?

Several factors may increase the risk of developing neuroendocrine tumors:

• Genetics: Inherited conditions like Multiple Endocrine Neoplasia type 1 (MEN1) or Von Hippel–Lindau syndrome.
• Family History: Having close relatives with neuroendocrine tumors or related syndromes.
• Age: Most neuroendocrine tumors occur in people over 50, though they can appear at any age.
• Lifestyle Factors: Smoking may raise the risk of lung neuroendocrine tumors.
• Chronic Conditions: Chronic conditions like atrophic gastritis, Zollinger–Ellison syndrome, and inflammatory bowel disease can increase risk.

What Are the Symptoms of Neuroendocrine Tumors?

Neuroendocrine tumor symptoms vary widely depending on tumor type, size, and whether it produces hormones.

Early signs (often vague or overlooked):

• Abdominal pain or discomfort
• Unexplained weight loss
• Persistent cough or wheezing (lung NETs)
• Changes in bowel habits

Hormone-related symptoms (functional NETs):

• Flushing (sudden redness and warmth of the skin)
• Diarrhea
• Low blood sugar (insulinomas)
• Stomach ulcers (gastrinomas)
• Wheezing, palpitations, flushing, and watery diarrhea (carcinoid syndrome)

Advanced symptoms:

• Fatigue
• Severe abdominal pain
• Yellowing of the skin (jaundice) if the liver is affected
• Bone pain if cancer has spread

How Are Neuroendocrine Tumors Diagnosed?

Doctors use several tests to confirm a neuroendocrine tumors diagnosis:

• Blood and Urine Tests: Blood tests measure markers like Chromogranin A (CgA), which is elevated in most neuroendocrine tumors, and specific hormones produced by the tumor, such as serotonin levels or hormones like gastrin. Urine tests check for elevated levels of hormones or their breakdown products, like 5-HIAA (a serotonin breakdown product).
• Imaging Scans: CT and MRI provide detailed cross-sectional images to help locate tumors, determine their size, and assess how far they have spread. Special PET scans, like Gallium-68 PET/CT, use radioactive tracers that bind to neuroendocrine cells, "lighting them up" to reveal tumor locations, including distant metastases.
• Endoscopy or Colonoscopy: A thin, flexible tube with a camera is inserted into the body to visualize tumors and collect tissue samples in the GI tract.
• Biopsy: A small sample of tissue or cells is removed from the suspected tumor. A pathologist then examines the sample under a microscope to confirm it is a neuroendocrine tumor, determine its specific type, and assess its grade (aggressiveness).

Staging of Neuroendocrine Tumors

Neuroendocrine tumor staging is determined using systems like the AJCC TNM system and involves assessing the tumor's size and spread (T), involvement of lymph nodes (N), and presence of distant metastasis (M), alongside a grading system (G) that reflects the tumor's growth rate.

• Stage 1: The tumor is small and contained within the organ.
• Stage 2: The tumor is larger but hasn't started to spread into the surrounding tissues.
• Stage 3: The tumor is larger and it may have started to spread into surrounding tissues and nearby lymph nodes.
• Stage 4: The tumor has spread to other body organ.

Grading describes how quickly tumor cells grow and divide:

• Low grade: Slow-growing
• Intermediate grade: Moderately fast
• High grade: Aggressive and fast-growing

Staging and grading guide doctors in choosing the best treatment plan.

What Are the Treatment Options for Neuroendocrine Tumors?

Surgery: 

• The primary treatment for many NETs, aiming to remove the entire tumor and surrounding healthy tissue.

Medical Treatments:

• Chemotherapy, which uses strong drugs to kill tumor cells and may be used for advanced tumors or those that recur after surgery, is useful for aggressive or advanced neuroendocrine tumors.
• Somatostatin Analogs, which mimic the hormone somatostatin, can slow tumor growth and help control symptoms caused by the tumor.
• Peptide Receptor Radionuclide Therapy (PRRT) combines a drug that targets cancer cells with a small amount of radioactive substance, which is delivered to the tumor through an IV.
• Targeted therapy drugs like everolimus or sunitinib block signals that help tumors grow.
• Radiation Therapy: Focused radiation can shrink tumors or relieve symptoms.

Proton Therapy: When Is It Applicable?

Proton therapy is a type of radiation therapy that uses protons instead of X-rays. It can be used for certain neuroendocrine tumors, particularly those in brain and skull base areas, to precisely target and destroy cancer cells while sparing surrounding healthy tissue and organs at risk.

This method offers a reduced radiation dose to healthy tissues compared to traditional radiation, which helps to minimize side effects and potentially preserve normal brain and neuroendocrine function. While still an area of research for many neuroendocrine tumors, the precise energy deposition of proton beams makes it a promising tool for treating difficult-to-reach tumors and improving patient quality of life. It is not standard for all NETs, but useful in selected cases where conventional radiation risks damaging nearby critical organs.

What Is the Prognosis for Neuroendocrine Tumors?

The outlook for neuroendocrine tumors depends on type, grade, and stage. Many low-grade neuroendocrine tumors grow slowly, and patients may live for years with proper treatment.

Survival Rates:

• Localized NETs: High survival rates (over 90% in some cases).
• Advanced NETs: Prognosis varies but treatment can still control symptoms and improve life expectancy.

Other factors affecting prognosis include the patient’s overall health, response to treatment, and whether the tumor produces hormones. High-grade neuroendocrine carcinomas behave more aggressively, with lower survival rates.

Screening and Prevention of Neuroendocrine Tumors

There are no universal screening guidelines for neuroendocrine tumors. However, people with a family history of genetic syndromes like MEN1 should undergo regular monitoring. For most people, maintaining general cancer-prevention habits, like not smoking, eating a balanced diet, and regular health checks, can aid early detection.

For International Patients

People from around the world come to Apollo Hospitals for the treatment of neuroendocrine tumors. Our international patient services team will guide you all the way from seeking the first virtual connect all the way to treatment in India and then returning home post treatment.

Services include:

• Medical opinions and scheduling
  • Pre-arrival medical review of reports and imaging.
• Travel and logistics
  • Assistance with visa invitation letters, airport transfers, and nearby accommodation options.
  • Dedicated international patient coordinators to guide through each step.
• Language and cultural support
  • Interpreter services in multiple languages.
  • Clear, simple explanations at every stage with written care plans.
• Financial coordination
  • Transparent treatment estimates and packages when possible.
  • Support with international payment methods and insurance coordination.
• Continuity of care
  • Shared records, imaging, and treatment summaries for home doctors.
  • Telemedicine follow-ups for convenience after returning home.

Frequently Asked Questions (FAQs)

1. What is the survival rate for neuroendocrine tumors?

Survival depends on the tumor’s location, stage, and grade. Many slow-growing neuroendocrine tumors have favorable long-term survival, while aggressive neuroendocrine tumors may need intensive treatment.

2. What are the treatment side effects?

Side effects vary. Surgery may cause pain or digestive changes, chemotherapy can lead to fatigue and hair loss, while hormone therapies may cause digestive upset, and PRRT may cause nausea, fatigue, or low blood counts. Your doctor will help manage these effects.

3. Can neuroendocrine tumors come back (recurrence)?

Yes, neuroendocrine tumors can recur even after treatment. Regular follow-up scans and blood tests are important.

4. How long is recovery after surgery for neuroendocrine tumors?

Recovery depends on the type of surgery. Many patients return to daily activities within a few weeks, though major abdominal surgery may require a longer recovery.

5. Can neuroendocrine tumors be cured?

Some neuroendocrine tumors are curable if detected early and removed surgically. Others can be managed long-term with treatments that control growth and symptoms.

6. What is the cost of treatment?

Costs vary widely based on the type of treatment and hospital facilities. At Apollo, costs are significantly lower compared to the US or Europe, while maintaining international standards. Apollo Hospitals offers cost estimates and financial counseling for patients.

7. Are neuroendocrine tumors rare?

Yes, but they are being diagnosed more often due to better awareness and advanced testing.