Intestinal Carcinoid Tumor Treatment & Management

Updated: Dec 20, 2021
  • Author: Rachel E Lewis, MD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Treatment

Approach Considerations

Surgical resection is the standard therapeutic modality for intestinal carcinoid tumors; medical care is usually only for symptomatic relief. Chemotherapy response rates are variable but rarely exceed 30%. When response does occur, the results are usually short-lived, lasting less than 1 year. 5-Fluorouracil and streptozocin (Zanosar)–based regimens are commonly used in patients with metastatic carcinoid tumors. The value of using newer agents (eg, taxanes, gemcitabine [Gemzar], irinotecan [Camptosar]) remains unproven.

Chemotherapeutic regimens are best used only for palliative purposes. If eligible, patients should be entered into a clinical trial of investigational therapy. Similarly, radiation therapy has only a palliative role, particularly for painful bony metastasis.

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Medical Care

High doses of sodium iodine-131–labeled metaiodobenzylguanidine, low-dose interferon-alfa, and octreotide have all been used, with some reduction in symptoms; however, tumor reduction is rarely observed. When reductions occur, they are only transient. [49] The somatostatin analog octreotide may provide control of carcinoid symptoms if findings on OctreoScan are positive or if somatostatin receptors are found in tumor tissue.

A randomized, placebo-controlled phase 3 trial found that everolimus plus octreotide long-acting repeatable (LAR) improved progression-free survival in patients with advanced neuroendocrine tumors associated with intestinal carcinoid syndrome. [50]

The US Food and Drug Administration (FDA) has approved the radiolabeled somatostatin analog Lutathera (lutetium Lu 177 dotatate) for the treatment of adult patients with somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), which would include intestinal carcinoids. Approval was based on the results of two studies: the first showed longer progression-free survival for patients taking Lutathera with octreotide compared with patients who received octreotide alone; the second showed complete or partial tumor shrinkage in 16% of 360 patients with GEP-NETs treated with Lutathera. [51]

The North American Neuroendocrine Tumor Society (NANETS) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI) have published a practical consensus guideline for the administration of 177Lu-dotatate. The guideline covers patient screening, maintenance therapy requirements, treatment location and room preparation, drug administration, and patient release, along with radiation safety, toxicity monitoring, management of potential complications, and follow-up. To prevent interference with somatostatin receptor binding, the guideline recommends waiting at least 4 weeks after the last dose of long-acting somatostatin analog (SSA) therapy or at least 24 hours after the last dose of a short-acting SSA before administering 177Lu-dotatate. [52]  

Telostristat ethyl (Xermelo) is approved by the FDA for carcinoid syndrome diarrhea in combination with SSA therapy in adults inadequately controlled by an SSA. Telostristat ethyl is a prodrug that is metabolized to telotristat, which inhibits tryptophan hydroxylase, the rate-limiting step in serotonin biosynthesis.

The safety and efficacy of telotristat were established in a 12-week, double-blind, placebo-controlled trial in 135 patients who were experiencing 4 or more bowel movements per day despite the use of an SSA and were randomly assigned to add placebo or telotristat three times daily. Reduction in bowel movement frequency of ≥30% from baseline for ≥50% of the double-blind treatment period was observed in 44% of patients given telotristat ethyl 250 mg, 42% of those given telotristat ethyl 500 mg, and 20% of those receiving placebo. The FDA approved the 250 mg TID dosage regimen. [53]

Patients with problematic diarrhea usually benefit from antidiarrheal medication. Cyproheptadine and histamine-2 receptor blockers may work because they suppress the production of vasoactive amines or block their peripheral effects.

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Surgical Care

Surgical resection is the standard therapeutic modality. The operative approach varies with the location and extent of the tumor.

Appendiceal Carcinoids

For tumors smaller than 1.5 cm in greatest diameter that are confined to mucosa, appendectomy is adequate, with no need for follow-up care. Cure rates are 100%.

Tumors 2 cm or larger in diameter, those at the base of the appendix, or those with mesenteric lymphadenopathy are not common but are considered potentially malignant. Consider more aggressive surgery in the form of a right hemicolectomy and lymphadenectomy, similar to that performed for colonic adenocarcinoma.

Invasion of only the mesoappendix does not alter the long-term prognosis, but cecal involvement necessitates further surgery.

A study by Cashin et al investigated the use of cytoreductive surgery and intraperitoneal chemotherapy in patients with appendiceal adenocarcinoids. The study found that the completeness of cytoreduction score (CC) correlated with overall survival. Candidates for this treatment should be referred early in order to attain a better CC score. The study also confirmed that drugs used for colorectal cancer also seemed adequate for appendicial adenocarcinoid, although other drugs may be more active. [54]

Small Bowel Carcinoids

At laparotomy, perform a thorough examination of the small bowel because multiple lesions are fairly common.

Macroscopic tumor size is a fairly good indicator of malignant potential. For tumors smaller than 1 cm in diameter, local resection is usually adequate. Tumors larger than 1.5 cm have a risk of recurrence, hence the need for a segmental bowel resection with lymphadenectomy.

Rectal Carcinoids

Tumor size is of essence with regard to the extent of resection. A systematic review by McDermott et al concluded that carcinoids up to 1 cm in size that have no adverse features can be treated with endoscopic or local excision; management of tumors between 1 and 2 cm is controversial, but those up to 1.6 cm without adverse features are suitable for local or endoscopic excision, with careful histopathological assessment. [55]

In tumors of up to 1 cm in diameter, local excision or fulguration results in cure rates close to 100%. [56] Consider large tumors (≥2 cm) malignant, and manage them similarly to adenocarcinoma of the rectum, with extensive resection. Tumors of 1-2 cm can be treated either by limited or more aggressive resection, with each case is guided according to the size, invasive nature, and anatomic location.

All patients except for those with lesions smaller than 1 cm require conscientious follow-up care.

Metastatic Intestinal Carcinoids

Surgery is considered worthwhile in most cases because this is the best form of palliation, regardless of whether the tumor is of the secretory type. Tailor the procedure accordingly, and avoid attempts at major debulking procedures.

All patients with advanced-stage carcinoid tumors should be evaluated for possible multimodal surgical therapy. Primary tumors should be resected, even in the presence of distant metastases, to prevent future intestinal obstruction. The "wait and see" method of management of this slow-growing cancer no longer has merit. [57]

Obstructive small bowel lesions could be resected (if possible) or bypassed.

Multiple liver metastases in patients with carcinoid syndrome are resected, cauterized, or ablated with percutaneous alcohol injections, because this usually results in a dramatic relief of symptoms.

Hepatic artery ligation or embolization (eg, collagen fibers, gel foam, alcohol) can result in significant tumor necrosis and is of value in patients with bulky, inoperable, or symptomatic liver metastasis, with up to a 60% reduction of tumor bulk in some cases.

The videos below demonstrate bland embolization of the right hepatic artery in a patient with metastatic neuroendocrine tumors.

Bland embolization of the right hepatic artery in a patient with metastatic neuroendocrine tumors: Part 1. Courtesy of Memorial Sloan-Kettering Cancer Center.
Bland embolization of the right hepatic artery in a patient with metastatic neuroendocrine tumors: Part 2. Courtesy of Memorial Sloan-Kettering Cancer Center.
Postprocedure computed tomography scans after bland embolization of the right hepatic artery in a patient with metastatic neuroendocrine tumors. Courtesy of Memorial Sloan-Kettering Cancer Center.

Hepatic artery ligation or embolization can be combined with intrahepatic chemotherapeutic infusion. However, it can result in toxic effects, particularly fever, nausea, vomiting, and abdominal pain. Occasionally, the carcinoid symptoms may worsen. [58]

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Diet

As previously mentioned, patients may experience symptoms due to NETs or treatment with medications like somatostatin analogs; these may include diarrhea, abdominal pain, flatulence, bloating, skin changes, and fatigue. Key nutritional recommendations for symptoms are listed below [59] :

  • For prevention of flushing, avoidance of spicy foods and alcoholic beverages
  • For prevention of diarrhea, substitute raw, high-fiber fruits and vegetables
    • Introduce ripe bananas, pureed vegetables, cooked fruits, rice, pasta, and potatoes
    • Avoid cream cheese, butter, and white breads - use jams, jellies, and whole-grain breads instead
    • Replace cream-based soups with broth
    • Replace doughnuts and butter cookies with pretzels or crackers
    • Ingest high-electrolyte replacement drinks in place of sodas or juices
    • Ingest lactose-free beverages in place of milk
  • Niacin supplementation to replenish low stores due to high metabolism of tryptophan associated with NETs
  • Pancreatic enzyme supplementation for steatorrhea or other symptoms associated with fat malabsorption
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Long-Term Monitoring

Surveillance of treated carcinoid patients depends on the initial stage at presentation and the type of treatment that was offered, as follows:

  • For appendicular carcinoids that are less than 2 cm and localized to the appendix, no further follow-up is required after the patients have had an appendectomy
  • For those patients who have had a right hemicolectomy, blood markers (5-HIAA, chromogranin A) need to be monitored at 3 months after resection, along with imaging in the form of a CT scan or MRI
  • For rectal carcinoids 2 cm or less, which have been amenable to transanal excision, follow-up is required in the form of a proctoscopy at 6 and 12 months, and further investigations are warranted only if clinically indicated
  • For other patients with intestinal carcinoid tumors, long-term monitoring is required. This involves blood markers every 6 months for the first 3 years and then yearly thereafter; additional imaging is performed based on the results of the markers and clinical findings [60]

 

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