Neuroendocrine Carcinoma Metastatic

When neuroendocrine tumors spread beyond their original location to other parts of the body, they become metastatic neuroendocrine cancer. While this represents an advanced stage of disease, many treatment options exist to manage symptoms, slow tumor growth, and help patients maintain quality of life for years.

Table of contents

• What is Metastatic Neuroendocrine Cancer?
• Causes and Risk Factors
• Recognizing the Symptoms
• Diagnosis and Staging
• Common Sites of Metastasis
• Treatment Options
• Living with Metastatic Neuroendocrine Cancer

What is Metastatic Neuroendocrine Cancer?

Neuroendocrine cancer originates from specialized neuroendocrine cells (cells that combine traits of nerve cells and hormone-producing cells) found throughout the body, primarily in organs such as the lungs, pancreas, gastrointestinal tract, and adrenal glands. These cells play a vital role in regulating various body functions, including hormone secretion and nerve signaling.^[1]

When neuroendocrine tumors become cancerous and spread to other parts of the body, they are referred to as metastatic neuroendocrine cancer. The metastatic process (the spread of cancer from one part of the body to another) involves cancer cells breaking away from the primary tumor and traveling through the bloodstream or lymphatic system to form secondary tumors in distant organs or tissues.^[1]

Most neuroendocrine tumors are malignant, meaning they are cancerous. These tumors can release hormones that cause various symptoms throughout the body.^[2] While some neuroendocrine tumors grow slowly, others grow more quickly. The characteristics vary significantly based on the tumor type and location.^[3]

Causes and Risk Factors

The exact causes of metastatic neuroendocrine cancer remain unknown. Researchers don’t know what triggers the abnormal cell growth that causes these tumors to form and spread.^[3]

However, several risk factors have been identified that may increase the likelihood of developing these tumors. Some individuals may have a genetic predisposition to neuroendocrine tumors due to certain hereditary conditions. Your risk of developing a neuroendocrine tumor increases if you have one of these inherited syndromes:^[1][3]

• Multiple endocrine neoplasia types (MEN1 and MEN2) – conditions that cause overactive tumors to form in various organs and endocrine system glands
• Von Hippel Lindau syndrome – a hereditary condition affecting various organs
• Neurofibromatosis type 1 (NF1) – a condition affecting nerve tissue growth
• Medullary thyroid cancer

Another significant factor is delayed diagnosis. In fact, 60% of neuroendocrine tumor patients are at Stage 4 (metastatic stage) at the time of correct diagnosis.^[1] This highlights the challenge of identifying these cancers early, as symptoms can be vague and easily attributed to other conditions.

Recognizing the Symptoms

Symptoms of metastatic neuroendocrine cancer can vary widely depending on the subtype and location of the tumor. Often, neuroendocrine tumors don’t cause symptoms until a tumor impacts an organ.^[3] Recognizing these symptoms early can lead to prompt diagnosis and appropriate treatment.

Common symptoms may include:^[1][3]

• Abdominal pain – Discomfort or pain in the abdominal area, especially in cases involving gastrointestinal neuroendocrine tumors
• Coughing and respiratory symptoms – Persistent cough, wheezing, or difficulty breathing, particularly with lung neuroendocrine tumors. Some patients may cough up blood
• Hormone-related symptoms – Some neuroendocrine tumors produce hormones that lead to symptoms like flushing, diarrhea, or changes in blood sugar levels
• Unexplained weight loss – Significant and unexplained weight loss over a relatively short period
• Fatigue – Persistent tiredness and weakness that doesn’t improve with rest
• Nausea and vomiting
• Shortness of breath

It’s important to remember that having these symptoms doesn’t always mean you have cancer. Many of these symptoms are common to less serious conditions. However, if you’re experiencing symptoms that don’t improve, talk to a healthcare provider.^[3]

Diagnosis and Staging

Diagnosing and staging metastatic neuroendocrine cancer is a careful process involving various medical assessments. The specific tests used will depend on the patient, their condition, and the location of the tumor.^[1]

Imaging Studies

Imaging studies create pictures of the inside of the body to visualize tumors, their size, and their spread to nearby organs or lymph nodes. Several types of imaging may be used:^[1][13]

• CT scans (Computed Tomography) – Use X-rays to create detailed cross-sectional images of the body
• MRI scans (Magnetic Resonance Imaging) – Use magnets and radio waves to create detailed images of soft tissues
• Ultrasound – Uses sound waves to create real-time pictures of internal organs
• PET scans (Positron Emission Tomography) – Detect neuroendocrine tumors based on how they interact with radioactive tracers. A specialized type called a DOTATATE PET scan or somatostatin receptor PET scan is particularly useful for slow-growing neuroendocrine tumors

Because neuroendocrine metastases are often highly vascular (have many blood vessels), they may be difficult to see on standard CT scans. Dynamic scanning with contrast material during both arterial and portal phases of blood flow helps ensure metastases aren’t missed.^[4]

Blood and Urine Tests

These tests indicate the level of proteins or hormones in your body made by neuroendocrine tumors. Your provider will use the results to confirm the presence of tumors and determine how fast a tumor may grow or spread.^[9] Some neuroendocrine tumors produce specific hormones that can be measured and act as tumor markers.^[4]

Biopsy

A biopsy (a procedure to remove a sample of tissue for laboratory testing) is often performed to confirm the diagnosis. In the lab, tests can show whether cancer cells are present and what type they are. How a biopsy is done depends on where the cancer is located in the body.^[13] When metastatic neuroendocrine tumors are discovered, the pathologist examines the tissue to try to identify the primary tumor site.^[7]

Common Sites of Metastasis

The most common sites of metastasis for neuroendocrine tumors include the liver, lungs, and lymph nodes.^[1] The liver is particularly frequently affected, with spread to the liver occurring from neuroendocrine tumors of the foregut, midgut, and hindgut.^[4]

Neuroendocrine liver metastases are usually multiple and of varying size. In most cases, both lobes of the liver are affected, though widespread seeding throughout the liver is seen only occasionally.^[4] The frequency of liver metastases varies by tumor type. For example, insulinomas (a type of pancreatic neuroendocrine tumor) seldom cause liver metastases, whereas more than 50% of patients with other types of pancreatic neuroendocrine tumors have liver metastases by the time of diagnosis.^[4]

Treatment Options

Treatment for metastatic neuroendocrine cancer is complex and involves a variety of options. A number of factors such as proliferation rate (how fast cells divide), degree of differentiation (how much cancer cells resemble normal cells), functionality (whether the tumor produces hormones), and extent of disease are used to tailor treatment accordingly, ideally in the context of a multidisciplinary team.^[10]

Surgery

Surgery remains the treatment of choice with an intention to cure. It may also be recommended in some cases of metastatic disease, even for tumors that have spread to other organs, and for difficult to control hormone-related symptoms.^[10][11] Experienced surgeons may perform extensive removal of liver tumor metastases in carefully selected patients.^[20]

Somatostatin Analogs

Long-acting somatostatin analogs (medications that mimic a natural hormone that inhibits hormone release) constitute the main treatment for the majority of functioning tumors. These medications can block the growth hormone that feeds slow-developing tumors. Patients typically receive monthly injections of drugs like lanreotide or octreotide.^[10][20] These treatments not only control symptoms but also slow tumor growth.^[14]

Peptide Receptor Radionuclide Therapy (PRRT)

PRRT combines a targeting molecule that binds to specific receptors on tumor cells with a radioactive particle that destroys cancer cells. It is given to patients through an IV infusion and has fewer side effects than other chemotherapies. A course of treatment typically includes four doses given eight weeks apart.^[20]

Other Systemic Therapies

In patients with advanced disease not amenable to surgical removal, additional treatment options include:^[10][14]

• Molecular targeted agents – Drugs that target specific molecules involved in cancer growth
• Chemotherapy – Medications that kill rapidly dividing cells
• Immunotherapy – Treatments that help the immune system fight cancer

Locoregional Therapies

For liver metastases, various locoregional treatments may be used to destroy tumors directly in the liver while limiting damage to healthy tissue.^[10][11]

Symptom Management

Specific medications may be used to control hormone-related symptoms. For example, evolving agents such as telotristat may be used for the control of carcinoid syndrome (a group of symptoms caused by hormones released by certain neuroendocrine tumors) and related complications.^[10]

The ideal time of treatment initiation and sequence of administration remain areas of active research and clinical judgment.^[10] Treatment decisions are best made by an experienced multidisciplinary team.^[14]

Living with Metastatic Neuroendocrine Cancer

Living with metastatic neuroendocrine cancer presents unique challenges. Many neuroendocrine tumors grow slowly, which means patients may live with their cancer for many years. This creates a balance between feeling well and knowing cancer is present in the body.^[20]

Emotional and Psychological Support

Coping with neuroendocrine cancer can be difficult. You may have ongoing symptoms that are hard to control and treatments that other people don’t understand. You may experience a range of emotions including shock, fear, confusion, anger, guilt, and sadness.^[19] These feelings are normal, and everyone reacts in their own way.

Talking to your friends and relatives about your cancer can help provide support. Some people find it easier to talk to someone other than their own friends and family, such as a counselor or support group members.^[19] Dedicated medical professionals and support networks are available to provide guidance, care, and compassion throughout this process.^[1]

Managing Daily Life

With appropriate treatment and support, many patients continue to work, exercise, travel, and maintain relationships.^[20] Practical strategies that may help include:^[19]

• Making lists to help organize tasks
• Using a calendar to track all appointments
• Setting achievable goals
• Planning enjoyable activities
• Staying as active as your condition allows

Information and Decision-Making

You may be more able to cope and make decisions if you have information about your type of cancer and its treatment. However, taking in information can be difficult, especially when newly diagnosed. It’s okay to ask for information to be explained again or to wait until you feel ready to learn more.^[19] Make a list of questions before appointments and consider bringing someone with you to help remember the information discussed.

Ongoing Monitoring

Even with metastatic disease, many patients maintain good quality of life with regular monitoring and treatment adjustments as needed. Every patient’s experience is unique, and treatment plans are individualized based on each person’s specific situation.^[1]

With early detection, appropriate treatment, and a strong support system, individuals can navigate the challenges posed by metastatic neuroendocrine cancer. While the disease is chronic, many people live active, fulfilling lives for years after diagnosis.^[1]