Can a patient with a resected pancreatic neuroendocrine tumor (PNET) and low tumor burden metastasis to the liver expect a normal life span?

From the Guidelines

Yes, it is possible to live a normal life span with metastatic pancreatic neuroendocrine tumors (NETs) that have spread to the liver, especially with a low tumor burden. According to the most recent and highest quality study available, which is the 2020 ESMO clinical practice guidelines for diagnosis, treatment, and follow-up of gastroenteropancreatic neuroendocrine neoplasms 1, a surgical approach can be considered in selected patients with stage IV GEP-NETs who have exclusive or predominant liver involvement. The guidelines suggest that a curative resection (R0, R1) of GEP-NETs with liver metastases is associated with a 5-year overall survival rate of around 85%.

Management typically includes a multidisciplinary approach with surgical resection of the primary tumor (which has already been done in this case), followed by targeted treatments for the liver metastases. These may include liver-directed therapies such as radiofrequency ablation, transarterial chemoembolization, or selective internal radiation therapy. Systemic treatments often include somatostatin analogs like octreotide LAR (20-30 mg every 4 weeks) or lanreotide (120 mg every 4 weeks), which can control hormone secretion and slow tumor growth. For progressive disease, targeted therapies such as everolimus (10 mg daily) or sunitinib (37.5 mg daily) may be used. Peptide receptor radionuclide therapy (PRRT) with lutetium-177 dotatate is another effective option for controlling metastatic disease.

Some key points to consider in the management of metastatic pancreatic NETs include:

• The role of palliative resection of primary tumors in advanced disease is controversial, but it may be beneficial in preventing complications related to bowel obstruction or intestinal ischemia 1.
• Debulking surgery may be recommended for alleviating symptoms of the carcinoid syndrome in patients with metastatic functioning SI-NETs 1.
• Liver transplantation may be a valid option in very selected patients with unresectable liver metastases who meet specific criteria, including absence of extrahepatic disease and stable disease in response to therapy for at least 6 months before transplant consideration 1.
• Regular monitoring with imaging (typically every 3-6 months initially) and biomarker testing is essential to track disease progression and adjust treatment accordingly.

Prognosis is influenced by factors including tumor grade, proliferation rate (Ki-67 index), and functional status, but with modern treatments, many patients with low-volume metastatic disease can maintain good quality of life and extended survival. As noted in the 2018 NCCN guidelines insights: neuroendocrine and adrenal tumors 1, a recent study of 172 patients who underwent hepatic resection of metastatic NETs showed that long-term survival can be achieved in selected cases, with a 10-year overall survival rate of 50.4%.

From the Research

Metastatic Pancreatic Net and Life Expectancy

• The provided studies do not directly address the question of living a normal life span with a metastatic pancreatic net where the main tumor was resected but later found to have spread to the liver with a low tumor burden 2, 3, 4, 5, 6.
• However, it is known that metastasis is a complex and systemic disease that develops as a result of interactions between tumor cells and their local and distant microenvironments 5.
• The process of metastasis involves several steps, including invasion of adjacent tissues, intravasation, transport of cancer cells through the circulatory system, arrest at a secondary site, extravasation, and growth in a secondary organ 4, 6.
• Understanding the molecular mechanisms underlying the metastatic process is crucial for developing novel therapeutic strategies aimed at contrasting the dissemination of cancer 4.
• Recent studies have highlighted the importance of immune-related changes in limiting or enabling the development of metastatic disease, and the success of immunotherapy in a subset of cancer patients is an example of how modulating the microenvironment and tumor-immune cell interactions can be exploited for the effective eradication of even advanced-stage tumors 5.

Treatment Options and Prognosis

• The use of somatostatin analogs, such as octreotide and lanreotide, has been approved for the control of clinical syndrome associated with functioning neuroendocrine tumors (NET) and for tumor growth control in advanced low/intermediate grade NET 2, 3.
• However, the level of evidence for the use of these agents in specific clinical contexts is not absolute, and clinical decisions should be made on a case-by-case basis, taking into account the individual patient's characteristics and the specific tumor type 3.
• The prognosis for patients with metastatic pancreatic net is generally poor, but it depends on various factors, including the extent of tumor spread, the presence of symptoms, and the response to treatment 6.