Expert Guidelines for Monitoring Neuroendocrine Tumors: A Patient's Guide to Follow-Up Care

Table of Contents

• Introduction: Why Specialized Follow-Up Matters
• What Your Medical Records Should Include
• Understanding Tumor Classification Systems
• Detailed Follow-Up Schedule by Tumor Type
• When You Might Need More Frequent Monitoring
• Understanding Your Blood Tests and Tumor Markers
• Imaging Scans: What to Expect and When
• What This Means for Your Care
• Important Limitations to Consider
• Key Recommendations for Patients
• Source Information

Introduction: Why Specialized Follow-Up Matters

Neuroendocrine neoplasms (NENs), which include both neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs), require careful, lifelong monitoring by specialists. These rare tumors can develop in various organs throughout your body, including your digestive system, lungs, and thymus gland. Because they behave differently depending on their location and characteristics, your follow-up care needs to be tailored specifically to your individual situation.

This article translates expert consensus recommendations from the European Neuroendocrine Tumor Society (ENETS) regarding how often you should be monitored, what tests you need, and how your information should be documented. These guidelines were created by a international panel of specialists who gathered in Antibes, France in 2015 to establish standardized care recommendations.

The panel strongly recommends that follow-up occurs at specialized NEN centers or hospitals that work closely with such centers. What matters most isn't which type of doctor leads your care (oncologist, gastroenterologist, endocrinologist, pulmonologist, or surgeon) but that experienced NEN specialists are involved in your treatment decisions.

What Your Medical Records Should Include

Your medical documentation should comprehensively track your journey from diagnosis through all phases of treatment and monitoring. This creates a complete picture that helps your medical team make the best decisions for your care. According to the experts, your records should include:

• Basic identification and demographic information
• General health scores that measure your ability to perform daily activities
• Detailed medical history including:
  • Onset, extent, and severity of tumor-specific symptoms
  • Hormone-related syndromes if present
  • Family history and any inherited cancer syndromes
  • Other cancers you may have had
• Other health conditions including kidney and liver disease
• Blood test results for chromogranin A and relevant hormone levels
• Information about carcinoid heart disease if present
• Availability of tumor tissue samples and blood samples for future research

This thorough documentation helps your medical team understand your specific tumor characteristics and how they might change over time. It also enables better comparison of data between different treatment centers, which ultimately helps improve care for all patients with neuroendocrine tumors.

Understanding Tumor Classification Systems

Your medical team will classify your tumor using several systems that help determine the appropriate follow-up schedule. These classification systems include:

• WHO Classification (World Health Organization) - Based on tumor differentiation and grading
• TNM Staging - Measures tumor size (T), lymph node involvement (N), and metastases (M)
• ENETS Consensus Guidelines - Specific recommendations for neuroendocrine tumors

The panel notes that a revised WHO classification was expected to be published soon after these guidelines, which might further refine the distinction between G3 neuroendocrine carcinomas (NEC G3, poorly differentiated) and G3 neuroendocrine tumors (NET G3, well differentiated). This distinction could impact treatment decisions but likely won't change the general follow-up recommendations.

It's important to understand that the evidence supporting specific follow-up intervals is limited. These recommendations represent the consensus of experts based on their clinical experience rather than strong scientific studies specifically designed to determine optimal monitoring schedules.

Detailed Follow-Up Schedule by Tumor Type

The following recommendations provide specific guidance based on where your tumor originated and its characteristics. These schedules represent the minimum recommended monitoring - your medical team may recommend more frequent follow-up based on your individual situation.

Bronchopulmonary (Lung) NENs:

• Typical carcinoid, resected: Follow-up every 6-12 months for 5-10 years with chromogranin A testing, relevant hormone markers, bronchoscopy, and CT/MRI/US scans
• Typical carcinoid, with residual tumor or metastases: More intensive monitoring every 3-6 months
• Atypical carcinoid, resected: Follow-up every 3-6 months for 1-3 years
• Atypical carcinoid, with residual tumor or metastases: Monitoring every 3 months
• Large-cell neuroendocrine carcinoma (LCNEC): Most intensive monitoring every 2-3 months

Thymic NENs:

• Typical, any status: Follow-up every 6-12 months
• Atypical, any status: Follow-up every 3-6 months
• Poorly differentiated: Most intensive monitoring every 2-3 months

Pancreatic NENs:

• Insulinoma, resected: Single follow-up at 3-6 months with fasting blood sugar, insulin, C-peptide, and pro-insulin testing
• Insulinoma, not resected: Follow-up every 3-6 months with the above tests plus imaging
• Gastrinoma: Follow-up every 3-6 months with gastrin, B12, calcium, and PTH testing
• Functional pancreatic NETs: Follow-up every 3-6 months with relevant hormone tests
• Nonfunctional pancreatic NETs: Follow-up every 3-6 months
• G3 pancreatic NEC/NET: Most intensive monitoring every 3 months

Small Intestine NENs:

• G1-G2, curatively resected: Follow-up every 6-12 months with chromogranin A and 5-HIAA testing
• G1-G2, with residual tumor or metastases: Follow-up every 3-6 months with additional heart monitoring for carcinoid syndrome
• G3 NEC/NET: Most intensive monitoring every 3 months

The guidelines provide similarly detailed recommendations for NENs of the esophagus, stomach, duodenum, appendix, colon, rectum, and cancers of unknown primary origin. Each specific recommendation takes into account the tumor's grade, whether it was completely removed, and whether it produces hormones.

When You Might Need More Frequent Monitoring

Your medical team may recommend shorter intervals between follow-up visits if you have certain high-risk features. According to the guidelines, these include:

• High-grade tumors (more aggressive cellular appearance)
• Large tumor burden (such as liver involvement >30% or lung/bone metastases)
• Extensive disease throughout the body
• Aggressive behavior (documented progression within few months)
• Severe uncontrolled endocrine symptoms
• Significant weight loss and clinical deterioration
• Very high chromogranin A levels (>10 times upper normal limit)

If you experience any of these situations, your medical team will likely recommend more frequent testing and monitoring to ensure timely intervention if your disease changes or progresses.

Understanding Your Blood Tests and Tumor Markers

Several blood and urine tests help your medical team monitor your neuroendocrine tumor. Each provides different information about your disease status.

Chromogranin A (CgA): This is the most common and reliable tumor marker for patients with G1 and G2 neuroendocrine tumors. However, it's important to know that:

• CgA is often normal in certain tumor types (nonfunctioning duodenal NEN, appendiceal NEN, small rectal NEN, and insulinomas)
• CgA levels can reflect tumor mass and changes in tumor burden
• Some studies show CgA may be prognostic, especially for small intestinal NEN
• A more than 25% increase from previous levels should prompt repeat testing and possibly imaging
• Many factors can falsely elevate CgA, including proton pump inhibitors, chronic atrophic gastritis, and decreased kidney or liver function
• Different laboratories use different testing methods, making direct comparison between centers challenging

Chromogranin B (CgB): This marker may be useful for monitoring bronchopulmonary and rectal NEN, but availability is limited.

Neuron-Specific Enolase (NSE): This marker may be helpful additional marker for patients with G3 NEN and has shown prognostic value in gastroenteropancreatic NEN.

5-Hydroxyindoleacetic Acid (5-HIAA): This urine test (24-hour collection) is an established marker for serotonin-producing tumors of the small intestine, appendix, and bronchopulmonary system, particularly when carcinoid syndrome is present. New blood tests for 5-HIAA are also becoming available. Important considerations:

• Many foods can affect results (avocado, banana, tomato, etc.)
• Several medications can interfere with testing (coumarin, paracetamol, phenacetin, aspirin, etc.)
• Your medical team will provide specific instructions on diet and medication restrictions before testing

Gastrointestinal Hormones: For functioning tumors (insulinoma, gastrinoma, etc.), the specific hormones they produce serve as diagnostic markers, though their value for prognosis is less certain.

NT-pro-Brain Natriuretic Peptide (NT-pro-BNP): This important test helps monitor for carcinoid heart disease in patients with carcinoid syndrome. Experts recommend testing at least yearly, supplemented by echocardiography or cardiac MRI.

Imaging Scans: What to Expect and When

Imaging plays a crucial role in monitoring your neuroendocrine tumor. The type and frequency of imaging depends on your specific tumor characteristics.

For G1 and G2 neuroendocrine tumors, which typically grow slowly, follow-up imaging is usually performed every 6-12 months. However, some patients may require more frequent imaging based on their individual situation. The optimal timing for imaging continues to be studied.

Cross-Sectional Imaging: This includes CT scans, MRI, and abdominal ultrasound. These tests help your medical team visualize the size and location of your tumors and monitor changes over time.

Somatostatin Receptor Imaging (SRI): This specialized imaging includes 68Ga-DOTA PET scans and octreotide scintigraphy. These tests are particularly useful because many neuroendocrine tumors have receptors for somatostatin, allowing for highly sensitive detection. SRI is recommended when it was positive at diagnosis and should be repeated based on your specific follow-up schedule.

FDG-PET-CT: This type of scan has higher sensitivity than SRI for patients with G3 neuroendocrine carcinomas and should be used instead for follow-up in this group. FDG-PET-CT is also frequently positive in aggressive G2 tumors with high Ki-67 indexes and in rapidly growing NEN.

Your medical team will determine the most appropriate imaging schedule based on your tumor type, grade, and behavior. They may also recommend additional procedures like endobronchial ultrasound (EBUS) or endoscopic ultrasound (EUS) if there's concern about recurrence or progression.

What This Means for Your Care

These detailed guidelines have several important implications for your neuroendocrine tumor care:

First, they emphasize the importance of specialized care at centers with experience managing neuroendocrine tumors. The complexity of these tumors and their varied behavior requires expertise that may not be available at all treatment facilities.

Second, they highlight the need for individualized care plans. Your follow-up schedule should be tailored to your specific tumor type, location, grade, and behavior rather than following a one-size-fits-all approach.

Third, they acknowledge the lifelong nature of neuroendocrine tumor monitoring. Even after successful treatment, ongoing surveillance is typically recommended due to the possibility of late recurrence.

Fourth, they recognize the importance of multidisciplinary care. Your medical team should include specialists from various fields who collaborate regularly through tumor boards to review your case and make collective decisions about your care.

Finally, they provide a framework for standardized documentation that enables better communication between your healthcare providers and facilitates research that can improve future care for all neuroendocrine tumor patients.

Important Limitations to Consider

While these guidelines represent the best available expert consensus, patients should understand several important limitations:

The panel repeatedly emphasizes that "evidence-based studies for follow-up are largely missing." This means these recommendations are based primarily on clinical experience rather than rigorous scientific studies specifically designed to determine optimal follow-up schedules.

The guidelines note that comparison of data between different centers is often challenging due to lack of standardization in how information is collected and documented. This variability can make it difficult to draw firm conclusions about what approaches work best.

There are significant variations in how tumor markers like chromogranin A are measured between different laboratories and using different testing kits. This means results may not be directly comparable if you change treatment centers or if your center changes testing methods.

The resource implications and growing costs of healthcare systems throughout Europe were considered when making these recommendations. In some cases, practical considerations about healthcare costs may influence what monitoring is available to you.

These guidelines specifically exclude small-cell lung cancer, as this is addressed in other guidelines and was considered beyond the scope of these recommendations.

Key Recommendations for Patients

Based on these expert guidelines, here are the most important recommendations for patients with neuroendocrine tumors:

1. Seek care at specialized centers with experience managing neuroendocrine tumors, or ensure your local hospital collaborates closely with such centers
2. Ensure multidisciplinary review of your case, preferably through regular tumor boards with expert panels
3. Follow the recommended monitoring schedule for your specific tumor type, grade, and status
4. Understand your tumor markers and what they mean for your individual situation
5. Maintain complete medical records that document your journey from diagnosis through all phases of treatment
6. Communicate any new symptoms or changes in your condition to your medical team promptly
7. Ask about appropriate imaging studies and make sure you understand their purpose and timing
8. Be aware that follow-up is typically lifelong, even after successful treatment
9. Understand the limitations of current knowledge about optimal follow-up strategies
10. Participate in research when possible to help improve future care for neuroendocrine tumor patients

Source Information

Original Article Title: ENETS Consensus Recommendations for the Standards of Care in Neuroendocrine Neoplasms: Follow-Up and Documentation

Authors: U. Knigge, J. Capdevila, D.K. Bartsch, E. Baudin, J. Falkerby, R. Kianmanesh, B. Kos-Kudla, B. Niederle, E. Nieveen van Dijkum, D. O'Toole, A. Pascher, N. Reed, A. Sundin, M.-P. Vullierme, all other Antibes Consensus Conference participants

Publication: Neuroendocrinology 2017;105:310-319

Received: November 8, 2016

Accepted: January 24, 2017

Published online: February 17, 2017

DOI: 10.1159/000458155

This patient-friendly article is based on peer-reviewed research and consensus guidelines from the European Neuroendocrine Tumor Society (ENETS).