When pancreatic neuroendocrine tumors spread beyond the pancreas to other organs such as the liver or bones, treatment shifts from cure to control—focusing on slowing disease progression, managing symptoms, and maintaining quality of life for as long as possible.

Understanding Your Treatment Path

Treating metastatic pancreatic neuroendocrine tumors is a complex journey that requires careful planning and a team of specialists working together. Unlike the more common form of pancreatic cancer called adenocarcinoma, pancreatic neuroendocrine tumors often grow more slowly, which means patients may live for years even after the cancer has spread^[6]. The goal of treatment is not always to eliminate the cancer entirely, but rather to control its growth, reduce symptoms, and help you maintain the best possible quality of life^[9].

The approach to treating your cancer depends on several factors. Doctors consider the size and location of tumors, whether they produce excess hormones (called functional tumors), how quickly the cancer cells are dividing, and your overall health and preferences^[2]. Because these tumors are rare and complex, it’s essential to work with a team that includes surgeons, oncologists, radiologists, and other specialists who understand neuroendocrine cancers^[13].

Treatment decisions are highly personalized. What works well for one person may not be the best choice for another. Your medical team will look at whether the tumors are well-differentiated—meaning they look more like normal cells and tend to grow slowly—or poorly differentiated, which means they’re more aggressive^[3]. These characteristics help doctors predict how the disease might behave and which treatments are most likely to help.

Standard Treatment Approaches

Even when pancreatic neuroendocrine tumors have spread to other organs, surgery remains an important treatment option for carefully selected patients. Removing as much tumor as possible, a procedure called debulking, can help control symptoms and slow disease progression^[6]. In some cases, surgeons can remove parts of the liver that contain metastases, or perform procedures to reduce the tumor burden in other affected organs.

For functional tumors that produce excess hormones causing troublesome symptoms, medications called somatostatin analogues are commonly prescribed. The two main drugs in this category are octreotide (often given as Sandostatin LAR) and lanreotide^[3][6]. These medications work by blocking the hormones that the tumor produces, which can relieve symptoms like severe diarrhea, flushing, and low blood sugar. Beyond symptom control, somatostatin analogues can also slow tumor growth in some patients. These drugs are typically given as injections once every four weeks.

Chemotherapy plays a role in treating metastatic pancreatic neuroendocrine tumors, particularly when the disease is progressing despite other treatments. Common chemotherapy combinations include capecitabine with oxaliplatin, or capecitabine with temozolomide (often called CAPTEM)^[3][16]. These drugs work by interfering with cancer cells’ ability to grow and divide. While chemotherapy can cause side effects such as fatigue, nausea, and increased risk of infection, many people are able to continue their daily activities during treatment with proper support and symptom management.

Targeted therapies represent a newer class of medications that attack specific molecular pathways cancer cells need to survive and grow. Everolimus is a targeted therapy that blocks a protein called mTOR, which helps control cell growth and division^[6]. Another targeted drug, sunitinib, blocks proteins that help tumors form new blood vessels. Both medications are taken as daily pills and have been shown to slow disease progression in patients with advanced pancreatic neuroendocrine tumors.

In March 2025, the U.S. Food and Drug Administration approved cabozantinib (CABOMETYX) for treating adults with well-differentiated pancreatic neuroendocrine tumors who have received previous treatment and cannot undergo surgery^[12]. In a Phase III clinical trial, patients who received cabozantinib had a median progression-free survival of 13.8 months compared to 3.3 months for those who did not receive the drug. This means the drug helped control the cancer for more than a year on average. The most common side effects included tiredness, decreased appetite, and nausea.

When tumors have spread primarily to the liver, specialized procedures called liver-directed therapies can be very effective. These include techniques like radiofrequency ablation, which uses heat to destroy tumor tissue, and embolization procedures that block blood flow to tumors^[6][9]. Radioembolization involves injecting tiny radioactive beads into blood vessels that feed the liver tumors^[16]. These treatments can shrink tumors, relieve symptoms, and improve quality of life without requiring major surgery.

In highly selected cases, liver transplantation may be considered for patients whose cancer is confined to the liver and cannot be removed by conventional surgery^[6][9]. This option is unique to neuroendocrine tumors and is not offered for most other types of metastatic cancer. However, only patients who meet very strict criteria are eligible, and the decision requires careful evaluation by a specialized transplant team.

Innovative Treatments in Clinical Trials

Peptide receptor radionuclide therapy, known as PRRT, represents an exciting advancement for treating metastatic pancreatic neuroendocrine tumors. This treatment combines a targeting molecule that seeks out and binds to tumor cells with a radioactive particle that destroys those cells^[13][16][17]. The therapy is given through an IV infusion, typically in four doses spaced eight weeks apart. Because the radioactive material specifically targets tumor cells that have certain receptors on their surface, PRRT can be effective while causing fewer side effects than traditional chemotherapy.

PRRT has shown promising results in clinical studies. Patients often experience tumor shrinkage or stabilization of disease, along with improvement in symptoms related to hormone-producing tumors. The treatment is generally well-tolerated, though some patients may experience temporary nausea, fatigue, or effects on kidney function. Not all treatment centers offer PRRT, as it requires specialized equipment and expertise, but availability has been expanding in recent years.

Researchers are actively investigating new targeted therapies and immunotherapies in clinical trials for pancreatic neuroendocrine tumors. These studies are testing drugs that work through different mechanisms than current standard treatments. For example, some trials are exploring medications that target specific genetic mutations found in neuroendocrine tumor cells, while others are examining whether drugs that help the immune system recognize and attack cancer cells might be effective.

Clinical trials for metastatic pancreatic neuroendocrine tumors typically progress through three phases. Phase I trials focus primarily on determining the safety of a new treatment and finding the appropriate dose. Phase II trials expand testing to more patients to evaluate whether the treatment shows evidence of working against the cancer. Phase III trials compare the new treatment directly with current standard treatments to determine if it offers meaningful benefits^[2].

Some clinical trials are investigating combination approaches, testing whether using two or more treatments together might be more effective than using them sequentially. Others are studying whether analyzing specific molecular markers in tumor tissue can help predict which treatments are most likely to work for individual patients. This approach, called precision medicine, aims to match each person with the treatment most suited to their tumor’s unique characteristics.

Eligibility for clinical trials depends on many factors, including the specific characteristics of your tumor, what treatments you’ve already received, your overall health, and the location of the trial. Trials are conducted at major cancer centers and specialized institutions around the world, including sites in the United States, Europe, and other regions. Your oncologist can help you identify trials that might be appropriate for your situation.

Most common treatment methods

• Surgery
  • Debulking surgery to remove as much tumor tissue as possible from the pancreas and liver
  • Liver resection to remove portions of the liver containing metastases
  • Liver transplantation in highly selected cases when cancer is confined to the liver
• Hormone therapy (Somatostatin analogues)
  • Octreotide (Sandostatin LAR) given as monthly injections to control hormone-related symptoms and slow tumor growth
  • Lanreotide administered monthly to block excess hormone production from functional tumors
• Chemotherapy
  • Capecitabine combined with oxaliplatin to interfere with cancer cell division
  • Capecitabine with temozolomide (CAPTEM regimen) particularly for progressive disease
  • More aggressive chemotherapy regimens for poorly differentiated tumors
• Targeted therapy
  • Everolimus that blocks the mTOR protein pathway controlling cell growth
  • Sunitinib that prevents tumors from forming new blood vessels
  • Cabozantinib (CABOMETYX) approved in 2025 for well-differentiated tumors after prior treatment
• Liver-directed therapies
  • Radiofrequency ablation using heat to destroy liver tumor tissue
  • Embolization procedures that block blood supply to liver metastases
  • Radioembolization with radioactive beads injected into liver tumor blood vessels
• Peptide receptor radionuclide therapy (PRRT)
  • Targeted radiation therapy delivered via IV infusion in four doses over several months
  • Combines targeting molecules with radioactive particles to destroy tumor cells
  • Particularly effective for tumors with specific surface receptors