Pancreatic neuroendocrine tumors are rare growths that develop in hormone-producing cells of the pancreas, and while they share the same organ location as the more common pancreatic cancer, they behave very differently, often growing more slowly and responding to a variety of specialized treatments.

What Treatment Options Mean for Patients

When someone receives a diagnosis of a pancreatic neuroendocrine tumor, also called a PNET or islet cell tumor, the first question is often about what can be done. Unlike many cancers where treatment choices feel limited, pancreatic neuroendocrine tumors can be approached from multiple angles, depending on how far the disease has progressed and what symptoms the person is experiencing. The main goal of treatment is not always to eliminate the tumor completely, especially when it has spread, but rather to control its growth, manage symptoms caused by excess hormone production, and help people maintain their quality of life for as long as possible.^[1][2]

Treatment decisions depend heavily on whether the tumor is classified as functional or nonfunctional. Functional tumors produce extra amounts of hormones like insulin, gastrin, or glucagon, leading to specific symptoms such as dangerous drops in blood sugar, severe stomach ulcers, or unusual skin rashes. Nonfunctional tumors do not cause hormone-related symptoms, but they can still create problems as they grow and press on surrounding organs or spread to other parts of the body. The stage of the disease—whether the tumor is still confined to the pancreas or has spread to the liver, bones, or lungs—also plays a critical role in shaping the treatment plan.^[3][2]

There are established treatments that have been used successfully for years, and there are also newer therapies being tested in clinical trials around the world. Medical societies and expert groups have developed guidelines to help doctors decide which treatments to use and when. However, because every person’s tumor behaves a bit differently, treatment is often personalized, taking into account the tumor’s size, location, grade (how fast the cells are dividing), and the patient’s overall health.^[9]

Standard Treatment Approaches

Surgery remains the cornerstone of treatment for pancreatic neuroendocrine tumors, especially when the tumor is localized and has not spread extensively. The type of operation depends on where the tumor is located within the pancreas. If the tumor is in the head of the pancreas, surgeons may perform a Whipple procedure, which removes the head of the pancreas along with parts of the small intestine, bile duct, and stomach. If the tumor is in the body or tail of the pancreas, a distal pancreatectomy may be performed, removing the tail and sometimes the spleen. When tumors are small and localized, complete removal can be curative, meaning the person may be free of disease after surgery.^[8][10]

Even when the cancer has spread, surgery can still play an important role. Some patients benefit from debulking surgery, where surgeons remove as much of the tumor as possible, even if they cannot remove it all. This can reduce symptoms and improve the effectiveness of other treatments. In cases where tumors have spread to the liver—a common site for metastasis—doctors may use interventional radiology techniques such as radiofrequency ablation or embolization. These procedures destroy or cut off the blood supply to liver tumors without major surgery.^[9][10]

For functional tumors that produce too much hormone, controlling those symptoms is a priority even before or alongside other treatments. Somatostatin analogues, such as octreotide and lanreotide, are injectable medications that mimic a natural hormone in the body. They work by blocking the release of other hormones from the tumor, which can reduce symptoms like severe diarrhea, flushing, and dangerously low blood sugar. These drugs are typically given as monthly injections and can also slow tumor growth in some patients. They are considered a standard treatment for managing symptoms and are often used long-term.^[9][15]

Targeted therapy drugs have become an important part of standard treatment. Everolimus is a pill that works by blocking a protein called mTOR, which cancer cells need to grow and divide. It has been shown to slow the progression of advanced pancreatic neuroendocrine tumors. Sunitinib is another targeted drug that blocks signals cancer cells use to form new blood vessels, essentially starving the tumor. Both drugs are taken daily and can cause side effects such as fatigue, mouth sores, skin rashes, high blood pressure, and changes in blood counts. Regular monitoring by a healthcare team is necessary to manage these effects.^[9][10]

A newer treatment option called peptide receptor radionuclide therapy, or PRRT, has been approved for use in pancreatic neuroendocrine tumors. This therapy combines a molecule that attaches to specific receptors on tumor cells with a radioactive particle that delivers targeted radiation. The most commonly used version is lutetium Lu 177 dotatate. It is given through an intravenous infusion, usually in four doses spaced eight weeks apart. PRRT can shrink tumors or slow their growth and tends to have fewer side effects than traditional chemotherapy. Side effects may include nausea, fatigue, and changes in kidney or bone marrow function, so patients are monitored closely during and after treatment.^[9][10]

Chemotherapy, which uses drugs to kill rapidly dividing cells, is less commonly used for well-differentiated pancreatic neuroendocrine tumors because they tend to grow slowly. However, it may be recommended for more aggressive, poorly differentiated tumors, or when other treatments have not worked. Common chemotherapy drugs for these tumors include temozolomide, capecitabine, streptozocin, and 5-fluorouracil. Chemotherapy can cause side effects such as nausea, vomiting, hair loss, fatigue, increased risk of infection, and damage to the bone marrow. Supportive care, including anti-nausea medications and blood count monitoring, is essential during chemotherapy treatment.^[9][10]

The duration of therapy varies widely depending on the treatment type and the individual response. Surgery is a one-time event, though recovery takes weeks to months. Somatostatin analogues and targeted therapies like everolimus or sunitinib are often continued for as long as they are working and side effects remain manageable, which can be months or even years. PRRT is typically given in a fixed course of four doses, though in some cases additional cycles may be considered. Chemotherapy regimens are usually given in cycles over several months, with breaks in between to allow the body to recover.^[9]

Emerging Treatments in Clinical Trials

Clinical trials are research studies that test new treatments before they become widely available. For pancreatic neuroendocrine tumors, these trials are exploring innovative drugs and approaches that may work better than current options, or that may help people whose tumors have not responded to standard treatments. Participating in a clinical trial can give patients early access to cutting-edge therapies, though it is important to understand that these treatments are still being studied for safety and effectiveness.^[9]

One area of active research is immunotherapy, which uses the body’s own immune system to fight cancer. Unlike chemotherapy, which directly kills cancer cells, immunotherapy trains immune cells to recognize and attack tumor cells. Several types of immunotherapy are being tested in pancreatic neuroendocrine tumors. Checkpoint inhibitors, such as drugs targeting PD-1 or PD-L1 proteins, have shown promise in some cancers, but results in pancreatic neuroendocrine tumors have been mixed. Researchers are studying whether combining checkpoint inhibitors with other treatments might improve outcomes. Early-phase trials (Phase I and Phase II) are assessing safety and looking for signs that these drugs can shrink tumors or slow their growth.^[9]

Another promising approach involves novel targeted therapies that attack specific molecular pathways within tumor cells. Scientists have discovered that some pancreatic neuroendocrine tumors have mutations or changes in genes related to cell growth and DNA repair. Drugs targeting these pathways are being developed and tested. For example, drugs that inhibit VEGF receptors or tyrosine kinases are being studied in combination with other treatments. These trials are often in Phase II or Phase III, meaning researchers are testing whether the drugs work better than current standards and are safe enough for regular use.^[9]

Recently, a new drug called cabozantinib (brand name CABOMETYX) was approved by the U.S. Food and Drug Administration for adults with well-differentiated pancreatic neuroendocrine tumors who have already received other treatments and cannot have surgery. This is a targeted therapy that blocks proteins involved in tumor growth and blood vessel formation. In a Phase III clinical trial involving patients with pancreatic neuroendocrine tumors, those who received cabozantinib had their cancer remain stable for a median of 13.8 months, compared to 3.3 months for those who did not receive the drug. About 18% of patients saw their tumors shrink. Common side effects include tiredness, loss of appetite, and nausea. This approval gives patients and doctors another important option when earlier treatments stop working.^[13]

Trials are also exploring combinations of existing treatments. For instance, researchers are testing whether adding immunotherapy to PRRT or combining two targeted drugs might be more effective than using one treatment alone. These combination studies are in various phases, from early safety testing (Phase I) to larger comparisons against standard care (Phase III). The goal is to find combinations that work synergistically—where the drugs enhance each other’s effects—without causing unacceptable side effects.^[9]

Clinical trials for pancreatic neuroendocrine tumors are being conducted in many countries, including the United States, Canada, Europe, and other regions. Eligibility for a trial depends on factors such as the stage and grade of the tumor, previous treatments received, overall health, and specific characteristics of the tumor (such as whether it has certain genetic mutations or receptor types). Patients interested in clinical trials should discuss options with their oncology team, who can help identify suitable studies and explain the potential benefits and risks.^[9]

Most common treatment methods

• Surgery
  • Whipple procedure for tumors in the head of the pancreas
  • Distal pancreatectomy for tumors in the body or tail of the pancreas
  • Debulking surgery to remove as much tumor as possible even when cure is not possible
  • Interventional radiology techniques like radiofrequency ablation or embolization for liver metastases
• Hormone therapy
  • Somatostatin analogues (octreotide, lanreotide) given as monthly injections to control hormone symptoms and slow tumor growth
• Targeted therapy
  • Everolimus, a pill that blocks the mTOR protein to slow tumor progression
  • Sunitinib, which blocks signals for new blood vessel formation in tumors
  • Cabozantinib, recently approved for advanced well-differentiated tumors after prior treatment
• Peptide receptor radionuclide therapy (PRRT)
  • Lutetium Lu 177 dotatate, an intravenous infusion that delivers targeted radiation to tumor cells, typically given in four doses over several months
• Chemotherapy
  • Temozolomide, capecitabine, streptozocin, or 5-fluorouracil, used mainly for more aggressive or poorly differentiated tumors
• Immunotherapy (in clinical trials)
  • Checkpoint inhibitors targeting PD-1 or PD-L1 to activate the immune system against tumor cells