Gastrointestinal neuroendocrine tumors (GI NETs) are rare malignancies that originate from neuroendocrine cells located throughout the gastrointestinal tract. [1] These tumors are unique because they can produce hormones and have a wide spectrum of behaviors, ranging from indolent to highly aggressive forms. [1]
Over the past few decades, the incidence of gastrointestinal neuroendocrine tumors has steadily increased worldwide.[1] According to data from the Surveillance, Epidemiology, and End Results (SEER) Program, the overall incidence of neuroendocrine tumors has risen by over 500% since the 1970s, with gastrointestinal sites accounting for a significant proportion of new cases. [1]
This rise, combined with advances in diagnostic techniques, has brought greater attention to innovative treatment options. Many patients are now seeking advanced treatment abroad, with Germany becoming a preferred country due to its advanced healthcare infrastructure, internationally accredited hospitals, and expertise in treating complex cancers.
Modern therapies, such as peptide receptor radionuclide therapy (PRRT) with Lutetium-177 and dendritic cell-based immunotherapy, are changing outcomes for patients, even in advanced stages.[8-10] With early detection and personalized treatment plans, many individuals with gastrointestinal neuroendocrine tumors can achieve significant remission and long-term survival, proving that recovery is indeed possible.
What Are Gastrointestinal Neuroendocrine Tumors?
GI NETs are a heterogeneous group of rare neoplasms arising from neuroendocrine cells dispersed throughout the gastrointestinal tract. These specialized cells possess both nerve and endocrine features, allowing them to produce and secrete hormones in response to various stimuli. NETs can develop in different organs. However, a significant proportion originates in the digestive system, known as gastrointestinal neuroendocrine tumors. [2]
GI NETs are classified based on their anatomical location:
- Esophagus – rare but typically aggressive
- Stomach – type gastric neuroendocrine tumors (gastric NETs) that are classified according to histology and clinical behaviors
- Small bowel – the small bowel, including the jejunum and ileum, is a frequent site of midgut NETs
- Appendix – generally small and slow-growing, often discovered incidentally
- Colon – tend to be larger and more aggressive at diagnosis
- Rectum – often found early due to routine colonoscopy screening
- Pancreas – referred to as pancreatic neuroendocrine tumors (PanNETs), these can be either functioning (hormone-producing) or non-functioning
The development of GI NETs is linked to several risk factors. Genetic syndromes, such as multiple endocrine neoplasia type 1 (MEN1), Von Hippel-Lindau disease, and neurofibromatosis type 1, significantly increase the risk. Other contributors include age (most cases occur between 50-70 years), smoking, and chronic inflammatory conditions of the gastrointestinal tract. [2]
NETs are broadly divided into functional and non-functional types. Functional NETs actively secrete hormones like serotonin, leading to symptoms such as flushing and diarrhea (carcinoid syndrome). In turn, non-functional NETs do not produce active hormones and are often detected later when they grow large enough to cause mechanical symptoms. [2] This classification and understanding of tumor biology help develop personalized treatment strategies aimed at improving outcomes for patients with gastroenteropancreatic neuroendocrine tumors.
Symptoms and Diagnosis of GI NETs
GI NETs are often referred to as "silent tumors" because they tend to grow slowly and remain asymptomatic until they reach an advanced stage. When symptoms do occur, they largely depend on whether the tumor is functional or non-functional and its anatomical location. [1, 3]
Common clinical manifestations include flushing, diarrhea, and abdominal pain. Less common symptoms include wheezing and heart valve lesions, which are characteristic of carcinoid syndrome caused by hormone secretion. Patients with large tumors may experience obstruction, bleeding, or weight loss. [1, 3]
The diagnosis of gastrointestinal neuroendocrine tumors requires a combination of biochemical, endoscopic, and imaging modalities.
- Blood and urine tests: Markers, such as chromogranin A (CgA) and 5-Hydroxyindoleacetic acid (5-HIAA), can suggest the presence of NETs.
- Endoscopy and colonoscopy: Direct visualization and biopsy are critical, especially for tumors in the stomach, colon, appendix, and rectum.
- Imaging: Cross-sectional imaging techniques, such as CT and MRI, help assess the extent of the disease. More advanced imaging like PET/CT with somatostatin analogs (e.g., Ga-68 DOTATATE) allows for high sensitivity in detecting even small lesions (e.g., in the pancreas).
- Biopsy: Histological confirmation is essential, with immunohistochemistry for markers like synaptophysin and chromogranin A.
An early and accurate diagnosis greatly enhances treatment options and improves outcomes for patients with gastric NETs and other gastrointestinal NETs. [1, 3] However, it is important to note that treatment strategies often depend on the classification of NETs by grade and differentiation.
Standard Treatment Options in Europe
Surgery is the primary method of treatment for localized neuroendocrine tumors. When detected early, complete surgical resection offers the best chance for long-term survival and potential cure. The type of surgery depends on the tumor's location. For example, gastric NETs may require partial or total gastrectomy, while tumors in the small intestine or colon often necessitate segmental resection. Surgery also helps manage symptoms in functional NETs by reducing hormone production and tumor burden. [4, 5]
Chemotherapy is generally reserved for patients with high-grade, poorly differentiated neuroendocrine carcinomas. These tumors are more aggressive and tend to respond better to cytotoxic agents. Although chemotherapy is less effective in well-differentiated NETs, it is a key option when rapid disease control is necessary, especially in metastatic settings. [1, 4-6]
Medications like somatostatin analogs (SSAs) are widely used to control hormone-related symptoms and to slow tumor progression. SSAs bind to somatostatin receptors expressed on tumor cells, reducing hormone secretion and inhibiting tumor growth. They are effective in patients with gastric and midgut NETs, providing symptom relief and improving progression-free survival with minimal side effects. [5, 7]
Innovative and Targeted Therapies
Lutetium-177 PRRT: Peptide Receptor Radionuclide Therapy
Peptide receptor radionuclide therapy (PRRT) with Lutetium-177 (Lu-177) is a highly targeted treatment for patients with advanced GI NETs that overexpress somatostatin receptors. This therapy involves binding a radioactive isotope, Lu-177, to a somatostatin analog (such as DOTATATE), which attaches to tumor cells and delivers localized radiation while sparing surrounding healthy tissues. [8]
The effectiveness of PRRT was confirmed in the NETTER-1 trial, where patients with advanced midgut NETs treated with Lu-177-DOTATATE experienced a 79% reduction in the risk of disease progression or death compared to those receiving high-dose octreotide LAR alone. [8] The study also demonstrated a median progression-free survival (PFS) of ~30 months in the PRRT group versus 8.4 months in the control group. [8]
Supporting these results, a German multi-center real-world registry study found a median PFS of approximately 41 months and a median overall survival of about 59 months in patients treated with Lu-177-DOTATATE. [9]
Dendritic Cell Therapy
Dendritic cell therapy is an innovative form of cancer immunotherapy designed to stimulate the patient's own immune system to recognize and destroy tumor cells. Dendritic cells are the most potent antigen-presenting cells in the body, responsible for initiating immune responses. In dendritic cell therapy, a patient's dendritic cells are harvested, loaded with tumor-specific antigens, and reintroduced into the body to "train" the immune system to target cancer cells. [10]
This therapy is based on the work of Ralph Steinman, who discovered dendritic cells and was awarded the Nobel Prize in Physiology or Medicine in 2011 for this discovery. His research became the foundation for therapeutic vaccines aimed at treating cancer and other diseases by utilizing the body's natural defenses. [10]
Clinical data on dendritic cell therapy for NETs involving various solid tumors, including gastrointestinal cancers, have shown that disease stabilization was achieved in 30%-40% of patients receiving dendritic cell vaccines. [10]
Interventional Radiology
Transarterial Chemoembolization (TACE) is a minimally invasive procedure used to treat liver metastases from GI NETs. It involves delivering chemotherapy directly to the liver tumors via the hepatic artery, followed by embolization to block blood flow and trap the drug in the tumor. This approach starves the tumor of nutrients and maximizes local chemotherapy exposure. Studies report that TACE achieves objective response rates of more than 90% and disease control rates up to 80% in NET liver metastases. [11] TACE is particularly useful for patients who are not candidates for surgical resection.
Fiorentini G et al Anticancer Res 2012;32:1387
Aliberti C et al Ancancer Res 2011;31:4581
Richardson A et al J Vasc Interv Radiol 2013;24:1209
Arterial Embolization (AE) – embolization without chemotherapy – is another option for liver-dominant disease. It focuses on obstructing the tumor's blood supply to induce ischemia. This method is generally considered less effective than TACE. Nevertheless, AE can be used in patients who cannot tolerate chemotherapy. Reported disease control rates range from 60% to 70%, with lower toxicity compared to chemoembolization. [12]
Radiofrequency Ablation (RFA) uses high-frequency electrical currents to generate heat and destroy tumor tissue. It is most effective for small tumors (less than 3 cm) and is commonly used for liver metastases in NET patients. Studies show local tumor control rates of 80-90% with RFA for well-selected patients. RFA is often recommended when surgical options are limited.
Microwave Ablation (MWA) is a similar technique to RFA but uses microwave energy to achieve higher temperatures and larger ablation zones, making it more effective for bigger tumors. Data suggest that MWA offers comparable or slightly better local control rates than RFA, with reported success rates exceeding 90% for NET liver metastases.
Cryoablation involves freezing tumor tissue, causing ice crystals to form and destroy cancer cells. It is advantageous for tumors near critical structures where heat-based ablation risks collateral damage. Although data specific to GI NETs are limited, in general oncology applications, local control rates around 70%-80% have been reported for cryoablation of liver metastases.
Electrochemotherapy (ECT) combines chemotherapy with locally applied electrical pulses that increase cell membrane permeability, enhancing drug uptake. Although ECT is still under investigation for gastrointestinal neuroendocrine tumors, early data report disease control rates of 70-85%.
| Therapy type | 2-Year Survival Rate | Response Rate | Duration | Side Effects |
|---|---|---|---|---|
| Standard Treatment | ~25% for advanced cancer | Less than 10% | Several cycles | Severe (nausea, fatigue, hair loss, immunosuppression, skin irritation) |
| Innovative Methods | ~60% for advanced cancer | 45-65% | Up to 4 sessions | Mild (localized discomfort) |
* Booking Health data
Medical Procedures Costs Around the World for GI NETs
| Treatment Method | GERMANY* | GB | USA |
|---|---|---|---|
| Standard Treatment | €80,000 - €150,000 full course | €90,000 - €165,000 full course | €100,000 - €180,000 full course |
| Innovative Methods | €25,000 - €60,000 full course | €70,000 - €120,000 full course | €100,000 - €150,000 full course |
*Prices may vary depending on the course of treatment and tumor characteristics
Treatment Options Abroad
For many patients diagnosed with gastrointestinal neuroendocrine tumors, seeking treatment abroad can offer access to more advanced and personalized care compared to what is available domestically. In several countries, especially in parts of Europe, treatment protocols may be limited by slower approval processes for new therapies or by restricted access to advanced technologies.
In contrast, leading European centers, particularly in Germany, provide access to innovative treatments such as Lutetium-177 PRRT, advanced interventional radiology methods, and personalized immunotherapies like dendritic cell therapy. German hospitals are known for their integration of advanced diagnostics, including Ga-68 DOTATATE PET/CT imaging, and multidisciplinary teams that develop tailored treatment plans for each patient.
In addition to offering some of the most advanced treatments, German hospitals are also recognized for their high standards of patient care, shorter waiting times, and transparent cost structures, enhancing the overall health outcomes for international patients. For many, choosing Germany means not only access to the best therapies but also a chance to improve their prognosis and quality of life.
Treatment in Germany
As mentioned above, Germany has established itself as a global leader in the treatment of GI NETs. Patients benefit from highly specialized cancer centers dedicated to the management of neuroendocrine tumors (NETs), where care is coordinated by multidisciplinary teams of oncologists, surgeons, radiologists, nuclear medicine specialists, and pathologists.
Treatment options in Germany go beyond conventional approaches, which significantly improve progression-free survival and quality of life for patients with gastric neuroendocrine tumors and gastric nets. Moreover, Germany also offers faster access to new therapies and clinical trials. In addition, many German cancer centers are actively involved in research and innovation, giving patients early access to the latest developments in neuroendocrine cancer care. As a result, Germany continues to attract patients from all over the world seeking the best possible outcomes for these rare and complex tumors.
Costs and How to Start Treatment Abroad
The cost of treatment for gastrointestinal neuroendocrine tumors can vary significantly depending on the country and the treatment method selected. In Germany, standard treatments, such as surgery and chemotherapy, range from €80,000 to €150,000, while innovative methods like Lutetium-177 PRRT and dendritic cell therapy typically cost between €25,000 and €60,000 for a full course. Compared to other countries, such as the USA or Great Britain, Germany offers both advanced medical care and more competitive pricing.
With companies like Booking Health, starting your treatment journey abroad is straightforward:
- Medical evaluation: Initial assessment of your medical records by leading specialists to develop a preliminary treatment plan.
- Document collection: Assistance in gathering and translating necessary medical documents for the selected hospital.
- Selection of hospital: Personalized matching with top hospitals in Germany based on the specifics of your case.
- Assistance with visas and travel: Full support in organizing travel, accommodation, and visa applications, ensuring an efficient process.
With Booking Health, patients with complex conditions like neuroendocrine tumors can gain access to world-class medicine and improve their health outcomes while receiving guidance every step of the way.
Choose the Best Treatment for Your Case with Booking Health
Finding the best treatment strategy for neuroendocrine tumors can be overwhelming. Many patients with gastrointestinal neuroendocrine tumors face exhausting journeys through multiple consultations, standard protocols, and complex information. In such a situation, it is easy to settle for conventional options, even if they offer limited outcomes and carry significant side effects. Fortunately, modern medicine offers advanced, personalized therapies that can make a real difference. The first step to accessing these therapies is making an informed choice.
Germany offers the most advanced treatments of gastrointestinal neuroendocrine tumors, combining innovative technologies like Lutetium-177 PRRT, TACE, and dendritic cell therapy with world-class expertise. German clinics deliver precision diagnostics and innovative care, helping patients with gastroenteropancreatic neuroendocrine tumors worldwide.
Booking Health has been arranging personalized cancer care for over 12 years. As a trusted partner, we provide comprehensive support at every stage of your medical journey:
- Assessment and analysis of medical reports
- Development of an individualized medical care program
- Selection of the most suitable hospital in Germany
- Preparation and forwarding of medical documents
- Pre-treatment consultations with leading clinicians
- Full support during the hospital stay
- Assistance with visas, travel arrangements, and accommodation
- Personal coordinator and interpreter services
- Transparent budgeting with no hidden costs
At Booking Health, we believe that health is a priceless asset that deserves the expertise of the best professionals. Let us help you access the best specialists and the latest treatment options for neuroendocrine tumors of the gastrointestinal tract.
Contact our medical consultant today to learn more about how personalized care in Germany can help you pursue better outcomes and a higher quality of life.
Modern Cancer Treatment: Patient Journeys with Booking Health
Frequently Asked Questions of Our Patients About Gastrointestinal Neuroendocrine Tumors
Send request for treatmentGastrointestinal neuroendocrine tumors are rare cancers that arise from neuroendocrine cells found in the lining of the digestive system. These tumors can produce hormones and are commonly located in the stomach, small intestine, colon, and rectum.
NETs of the gastrointestinal tract are often associated with genetic factors like multiple endocrine neoplasia type 1 (MEN1), chronic inflammation, or sporadic mutations. However, the exact cause is still under investigation.
Symptoms vary based on tumor location and type but may include gastric discomfort, duodenal ulcers, rectal bleeding, diarrhea, flushing, and abdominal pain. Many NETs remain asymptomatic until advanced stages.
Gastrointestinal neuroendocrine tumors are diagnosed through blood tests, imaging studies like PET/CT, and endoscopic biopsies. Gastric NETs are often detected during routine endoscopies.
The best treatment for gastrointestinal neuroendocrine tumors depends on tumor size, location, and spread. Options include surgery, PRRT with Lutetium-177, and targeted therapies.
Yes, Germany offers innovative therapies for NETs. Leading hospitals provide advanced options like PRRT, TACE, and dendritic cell immunotherapy for gastrointestinal neuroendocrine tumors.
Lutetium-177 PRRT is a targeted therapy for neuroendocrine tumors, delivering radiation directly to tumor cells that express somatostatin receptors and sparing healthy tissues.
Yes, immunotherapy options for gastrointestinal NETs include dendritic cell vaccines and clinical trials investigating checkpoint inhibitors.
Gastrointestinal neuroendocrine cancer survival rates vary by tumor grade and stage. For localized disease, 5-year survival can exceed 80%, but it decreases significantly in advanced cases.
Treatment costs in Germany for NETs range from €25,000 to €60,000 for innovative therapies and €80,000 to €150,000 for full standard treatment courses, depending on complexity.
Top hospitals in Germany for NET treatment include University Hospitals in Heidelberg, Munich, and Berlin, known for their expertise in gastrointestinal neuroendocrine tumors.
To start treatment abroad, Booking Health helps with medical evaluations, document preparation, hospital selection, travel arrangements, and full support throughout your treatment journey.
Surgery is often the first-line approach for localized gastrointestinal NETs, but in cases with metastases or inoperable tumors, alternatives like PRRT or embolization are preferred.
Functional gastrointestinal NETs produce hormones causing clinical symptoms like flushing or diarrhea, while non-functional NETs do not, often remaining silent until advanced stages.
Choose treatment abroad and you will be sure to get the best results!
Authors:
This article was edited by medical experts, board-certified doctors Dr. Nadezhda Ivanisova, and Dr. Vadim Zhiliuk. For the treatment of the conditions referred to in the article, you must consult a doctor; the information in the article is not intended for self-medication!
Our editorial policy, which details our commitment to accuracy and transparency, is available here. Click this link to review our policies.
Sources:
[1] JAMA Oncology. Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States. https://jamanetwork.com/journals/jamaoncology/fullarticle/2621997
[2] ScienceDirect. Nothing But NET: A Review of Neuroendocrine Tumors and Carcinomas. https://www.sciencedirect.com/science/article/pii/S1476558617303470
[3] The Lancet Oncology. Gastroenteropancreatic neuroendocrine tumours. https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(07)70410-2/abstract
[4] National Comprehensive Cancer Network. Neuroendocrine and Adrenal Tumors. https://www.nccn.org/login?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf
[5] Journal of the National Comprehensive Cancer Network: JNCCN. Neuroendocrine and Adrenal Tumors, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. https://jnccn.org/view/journals/jnccn/19/7/article-p839.xml
[6] Journal of Neuroendocrinology. European Neuroendocrine Tumor Society 2023 guidance paper for functioning pancreatic neuroendocrine tumour syndromes. https://onlinelibrary.wiley.com/doi/10.1111/jne.13318
[7] Journal of Clinical Oncology. Placebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients With Metastatic Neuroendocrine Midgut Tumors: A Report From the PROMID Study Group. https://ascopubs.org/doi/10.1200/JCO.2009.22.8510
[8] New England Journal of Medicine. Phase 3 Trial of 177 Lu-Dotatate for Midgut Neuroendocrine Tumors. https://www.nejm.org/doi/10.1056/NEJMoa1607427
[9] European Journal of Cancer. Effectiveness and side-effects of peptide receptor radionuclide therapy for neuroendocrine neoplasms in Germany: A multi-institutional registry study with prospective follow-up. https://www.ejcancer.com/article/S0959-8049(16)00047-2/abstract
[10] Nature Reviews Cancer. Cancer immunotherapy via dendritic cells. https://www.nature.com/articles/nrc3258
[11] Springer Nature Link. Transarterial chemoembolization for liver metastases of a pancreatic neuroendocrine neoplasm: a single-center experience. https://link.springer.com/article/10.1007/s00595-023-02714-9
[12] American Cancer Society. Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumors. https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.21389
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