TABLE 3.

Therapeutic Methods for the Management of Unresectable and Metastatic Gastroenteropancreatic Neuroendocrine Tumors (NETs)

Condition	Therapeutic Method	Category of Evidencea		Considerations
		Pancreatic NET	Gastrointestinal NET
Complete resection possible	Complete resection of primary and metastatic lesions	2A	2A	Resection of small asymptomatic primary tumors in the presence of unresectable metastases is not indicated
Asymptomatic stable disease, and low tumor burden	Observation	2A	2A	According to PROMID trial results, octreotide treatment is recommended for gastrointestinal NETs, and observation strategy needs a critical reevaluation
	Octreotide	§	2A	Octreotide treatment of pancreatic neuroendocrine tumors is not included in NCCN 2012 guidelines
Clinically significant tumor burden, progressive disease	Octreotide	2B	2A	Pancreatic NET: MTT or cytotoxic chemotherapy first or consider other methods
	MTT	2A	3	Gastrointestinal NET: octreotide and consider other methods
	Cytotoxic chemotherapy	2A	3	Ablative therapy or cytoreductive surgery: only if nearly complete resection or removal can be achieved
	Liver-directed therapy (transarterial embolization, ablative therapy, cytoreductive surgery)	2B	2B

Note—PROMID = 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, LAR = long-acting repeatable, MTT = molecular targeted therapy.

^aNational Comprehensive Cancer Network (NCCN) categories of evidence and consensus [4]: 1, on the basis of high-level evidence, there is NCCN consensus that the intervention is appropriate; 2A, on the basis of lower-level evidence, there is NCCN consensus that the intervention is appropriate; 2B, on the basis of lower-level evidence, there is NCCN agreement but not consensus that the intervention is appropriate; 3, on the basis of any level of evidence, there is major disagreement that the intervention is appropriate.