Treatment of Gastrointestinal Neuroendocrine Tumors, by Extent of Disease

Treatment of GI neuroendocrine tumors is based mostly on their size or how far they have grown into the wall of the organ where they started, as well as if they have spread.

Localized GI neuroendocrine tumors

If a tumor has not spread outside the organ where it started, it is localized.

Stomach

Neuroendocrine tumors of the stomach are generally grouped by:

• The level of a hormone called gastrin
• The amount of acid in the stomach measured before surgery

The levels of these substances determine the type of stomach neuroendocrine tumor(NET).

Type 1 NET: Patients with this type have high gastrin levels but low levels of stomach acid. These NETs tend to be small, but there may be many of them. The tumors don’t tend to grow into the deeper layers of the stomach or spread to other organs or tissues and are often treated by removing them completely using an endoscope. The other option is to watch the tumors closely (by endoscopy) and only remove them if they start growing.

Type 2 NET: Patients with this type have high gastrin and stomach acid levels. Like type 1 tumors, these are often small and there may be more than one at a time. Type 2 tumors also don’t tend to grow into deeper layers of the stomach or spread to other organs.

Small tumors can be watched closely without treatment, removed with endoscopy, or treated with octreotide or lanreotide to lower levels of gastrin and stomach acid. High doses of proton pump inhibitors, such as omeprazole or lansoprazole, may also be used to control  stomach acid.

For tumors larger than 2 cm (slightly less than an inch), watching the tumor closely isn’t usually an option. These tumors need to be removed, either by an endoscope or an incision in the abdomen that removes the tumor and some surrounding stomach tissue.

Type 3 NET: Patients with type 3 tumors have normal gastrin and stomach acid levels. There is usually only one tumor, and it tends to grow into deeper layers of the stomach or even spread to nearby lymph nodes or other organs (like the liver). If the tumor is small, endoscopic surgery may still be an option. More often, though, more extensive surgery is needed: removal of a piece of the stomach (partial gastrectomy ) and nearby lymph nodes.

Small intestine

Some small tumors in the duodenum, the first part of the small intestine, can often be removed through an endoscope (endoscopic resection). Depending on the size of the tumor and if it is growing into nearby tissues, other options include surgery to remove the tumor (local excision), removing all or part of the duodenum with nearby lymph nodes (duodenectomy), and removing the duodenum and part of the pancreas (a pancreatoduodenectomy).

For tumors in other parts of the small intestine, treatment is either local excision for small tumors or small bowel resection (removal of a piece of intestine). For larger tumors, some surrounding blood vessels and lymph nodes also will be removed.

Large intestine (other than appendix and rectum)

The usual treatment is removal of a section of colon along with nearby lymph nodes and blood vessels (hemicolectomy). Because many patients have more than one neuroendocrine tumor, the surgeon will often check the rest of the colon for other tumors during surgery. Sometimes, very small tumors can be removed using a colonoscope.

Appendix

Most often, removal of the appendix (appendectomy) is the only treatment needed for neuroendocrine tumors 2 cm across or smaller. Other factors, such as the way the tumor cells look, the patient's age, general health, and how much the patient is worried about the possibility of the cancer coming back, may also affect decision-making about more treatment.

Tumors larger than 2 cm are more likely to have already spread to nearby tissues and lymph nodes, so more extensive surgery is usually recommended. This means removing about a third of the colon next to the appendix (hemicolectomy), along with nearby blood vessels and lymph nodes. This procedure might not be recommended for people who are older or have other serious health problems because the benefits might not outweigh the risks.

Rectum

Most rectal neuroendocrine tumors that are smaller than 1 cm (slightly less than half an inch) can be removed by endoscope or local excision through the anus.

The best approach for a rectal neuroendocrine tumor between 1 and 2 cm depends on how deeply it has grown into the wall of the rectum, as well as if it has invaded nearby lymph nodes. Doctors can check for this before surgery by using a rectal endoscopic ultrasound. If the tumor has grown into the thick muscle layer of the rectum (the muscularis propria) or deeper or if local lymph nodes have cancer cells, it needs to be treated the same as a larger tumor. If not, it may still be able to be removed with an endoscope or local excision through the anus.

Tumors larger than 2 cm (and those that have grown deep into the wall of the rectum) have a higher risk of growing and spreading, so they are removed by the same operations used for adenocarcinomas (the usual type of rectal cancer). This operation is a low anterior resection (LAR) if the tumor is in the upper part of the rectum. If the lower part is involved, abdominoperineal resection (APR) and a colostomy are used.

Regional spread

Regional spread means that the cancer has either spread to nearby lymph nodes or has grown through the wall of the organ where it started and has invaded nearby tissues such as fat, ligaments, and muscle.

If possible, the primary (main) tumor and any areas of cancer spread should all be removed by surgery. Nearby lymph nodes should be removed and checked for signs of cancer spread. If this can't be done, surgery should remove as much cancer as possible without causing severe side effects. Surgery also should be done to relieve symptoms such as intestinal blockage caused by the local growth of the tumor.

If all of the cancer cannot be removed , treatment with somatostatin drugs, like octreotide or lanreotide, or targeted drugs, like everolimus, can be considered because they may control the remaining cancer.

Distant spread

At this stage, the cancer has spread to other organs such as the liver and a cure is not usually possible.  Treatment is not always needed right away, depending on how quickly the tumors are growing. The goal of surgery in this situation is usually to relieve symptoms and slow the course of the disease. For example, removing or bypassing areas blocked by cancer growth can relieve some symptoms. If distant metastases are not causing symptoms, treatment may not be needed.

If the cancer has spread to the liver, even when it isn’t causing symptoms, some doctors recommend treatment.  If metastatic tumors in the liver cannot be removed by surgery without causing severe side effects, ablation or embolization can be used to destroy as much of them as possible. 

If carcinoid syndrome is causing bothersome symptoms, treatment options include chemotherapy, targeted therapy, treatment with octreotide or lanreotide, or surgery to remove the metastatic tumors. Patients should also be advised to avoid alcoholic drinks, stress, strenuous exercise, spicy foods, and certain medicines that can make the symptoms of neuroendocrine syndrome worse.

Recurrent neuroendocrine tumors

When cancer comes back after treatment it is called a recurrence. A recurrence can be local (in or near the same place it started) or distant (spread to organs such as the lungs or bone). Sometimes patients with recurrent neuroendocrine tumors are treated with surgery. This provides the best chance for a good long-term outcome. If surgery is not possible, the treatments used for distant spread may be helpful. For more information, see Understanding Recurrence.

Neuroendocrine carcinomas

Gastrointestinal neuroendocrine carcinomas (NECs) are high-grade (grade 3) tumors that grow very quickly. There are also some low- (grade 1) and intermediate-grade (grade 2) neuroendocrine tumors that act like neuroendocrine carcinomas because they grow fast. These cancers are treated differently from most neuroendocrine tumors (grade 1 and 2) because they are treated with chemotherapy first.

Neuroendocrine heart disease

The substances released into the blood by some neuroendocrine tumors can damage the heart. Early symptoms are fatigue and shortness of breath. Eventually, patients get fluid in their legs and even their abdomen. The major cause is damage to the valves of the heart. Doctors can usually make the diagnosis by listening to the heart and by an ultrasound of the heart called an echocardiogram.

The main treatment is with a somatostatin analog like octreotide or lanreotide to block the effect of the tumor’s toxic substances. Drugs (diuretics) to get rid of extra fluid can also help. Sometimes, heart surgery may be needed to replace the damaged valves.