Treatment of Metastatic Gastrointestinal Neuroendocrine Tumors

Although the definitive role of surgery in patients with metastatic disease has not been established, conservative resections of the intestine, mesenteric tumors, and fibrotic areas may improve symptoms and quality of life substantially in patients with metastatic hepatic, mesenteric, and peritoneal neuroendocrine (carcinoid) tumors. If the condition of the patient is such that surgery is not a greater risk than the disease, the primary tumor should be resected to prevent an emergency presentation with obstruction, perforation, or bleeding.[1] Despite common acceptance that resection of at least 90% of the tumor burden is required to achieve palliation, approximately 60% of patients with surgery alone will experience symptom recurrence; the 5-year survival rate is between 35% and 80%, depending on the experience of the surgical center.[2,3] Because treatment with somatostatin analogues can achieve similar rates of symptom relief with fewer adverse effects, in each patient the benefits of surgical treatment of gastrointestinal neuroendocrine tumors should be weighed carefully against the potential risks of an open exploration. Tumor debulking, however, may potentiate pharmacological therapy by decreasing the secretion of bioactive substances.[4]

Management of hepatic metastases may include surgical resection; hepatic artery embolization; cryoablation and radiofrequency ablation; and orthotopic liver transplant. For more information, see the Treatment of Hepatic Metastases section. Cytoreductive surgery for hepatic metastases from gastrointestinal neuroendocrine tumors can be performed safely with minimal morbidity and mortality resulting in regression of symptoms and prolonged survival in most patients.[5] In one large review that included 120 patients with neuroendocrine tumors, a biochemical response rate of 96% and a 5-year survival rate of 61% were reported for patients whose hepatic metastases were resected surgically.[6][Level of evidence C2]

In the case of liver metastases, localization and resection of the primary tumor may be considered, even among patients in whom the primary neoplasm is asymptomatic. In a retrospective study involving 84 patients, 60 of whom had their primary neoplasm resected, the resected group had a greater median progression-free survival (PFS) of 56 months, compared with 25 months of PFS for the primary nonresected group (P < .001). Median survival time for the resected group was longer at 159 months when compared with 47 months for the nonresected group (P < .001).[7][Level of evidence C2]

Although the response of neuroendocrine tumors to external-beam radiation therapy is very limited, palliative radiation therapy has some efficacy for bone and brain metastases and in the management of spinal cord metastases.[4]

Treatment with single-agent chemotherapy or multiple-agent chemotherapy appears to be of little benefit in the management of gastrointestinal neuroendocrine tumors because no regimen has shown objective tumor response rates greater than 15%.[4]

Treatment with radionuclides such as iodine I 131-metaiodobenzylguanidine and lutetium Lu 177-octreotate may be of benefit. For more information, see the Radionuclides section.

Somatostatin analogues and interferon alfa are the primary agents used in the treatment of carcinoid syndrome. Management of the symptoms of carcinoid syndrome may also include dietary modification and the use of various antidiarrheal agents, antihistaminics for skin rashes, and theophylline or beta-2 adrenergic receptor agonists for bronchospasm. For more information, see the sections on Somatostatin Analogues, Interferons, and Symptomatic Therapy.

Information about ongoing clinical trials is available from the NCI website.