Pancreatic Neuroendocrine Tumor Stages

After someone is diagnosed with a pancreatic neuroendocrine tumor (NET), doctors will try to figure out if it has spread, and if so, how far. This process is called staging. The stage of a cancer describes how much cancer is in the body. It helps determine how serious the cancer is and how best to treat it. Doctors also use a cancer's stage when talking about survival statistics.

The stages of pancreatic NET range from I (1) through IV (4). As a rule, the lower the stage, the less the cancer has spread. A higher number, such as stage IV, means cancer has spread more. Although each person’s cancer experience is unique, cancers with similar stages tend to have a similar outlook and are often treated in much the same way.

How is the stage determined?

The staging system most often used for pancreatic NETs is the American Joint Committee on Cancer (AJCC) TNM system, which is based on 3 key pieces of information:

• The size and extent of the main tumor (T): How large is the tumor? Has it grown into nearby structures or organs?
• The spread to nearby lymph nodes (N): Has the cancer spread to nearby lymph nodes?
• The spread (metastasis) to distant sites (M): Has the cancer spread to distant organs? (The most common site of spread is the liver.)

Numbers or letters after T, N, and M provide more details about each of these factors. Higher numbers mean the cancer is more advanced. Once a person’s T, N, and M categories have been determined, this information is combined in a process called stage grouping to assign an overall stage. For more information, see Cancer Staging.

The system described below is the most recent version of the AJCC system, effective as of January 2018. It is used to stage well-differentiated pancreatic NETs, but not high-grade pancreatic NETs (known as neuroendocrine carcinomas) or other types of pancreatic cancer, which have their own staging system.

Pancreatic NETs are typically given a clinical stage based on the results of a physical exam, biopsy, and imaging tests (as described in Tests for Pancreatic Neuroendocrine Tumor). If surgery is done, the pathologic stage (also called the surgical stage) is determined by examining tissue removed during the operation. 

Staging for pancreatic NETs can be complex. If you have any questions about the stage of your cancer or what it means, please ask your doctor to explain it to you in a way you understand.

Stages of pancreatic neuroendocrine tumors

AJCC Stage	Stage grouping	Stage description*
I	T1 N0 M0	The tumor is less than 2 centimeters (cm) across and is still just in the pancreas (T1). The cancer has not spread to nearby lymph nodes (N0) or to distant parts of the body (M0).
II	T2 N0 M0	The tumor is at least 2 cm across but no more than 4 cm across, and it is still just in the pancreas (T2). The cancer has not spread to nearby lymph nodes (N0) or to distant parts of the body (M0).
	OR
	T3 N0 M0	The tumor is more than 4 cm across and is still just in the pancreas, OR the tumor has grown into the duodenum (the first part of the small intestine) or the common bile duct (T3). The cancer has not spread to nearby lymph nodes (N0) or to distant parts of the body (M0).
III	T4 N0 M0	The tumor has grown into nearby organs (such as the stomach, spleen, colon, or adrenal gland) or it has grown into nearby large blood vessels (T4). The cancer has not spread to nearby lymph nodes (N0) or to distant parts of the body (M0).
	OR
	Any T N1 M0	The tumor can be any size and might or might not have grown outside of the pancreas (any T). It has spread to nearby lymph nodes (N1), but not to distant parts of the body (M0).
IV	Any T Any N M1	The tumor can be any size and might or might not have grown outside of the pancreas (any T). It might or might not have spread to nearby lymph nodes (any N). The cancer has spread to distant parts of the body (M1).

* The following additional categories are not listed in the table above: 

• TX: The main tumor cannot be assessed due to lack of information. 
• T0: There is no evidence of a main tumor.
• NX: Nearby lymph nodes cannot be assessed due to lack of information. 

Other prognostic factors

Although not formally part of the TNM system, other factors can also be important in determining a person’s prognosis (outlook).

Tumor grade

The grade describes how quickly the cancer is likely to grow and spread. For pancreatic NETs, an important part of grading is measuring how many of the cells are in the process of dividing into new cells. This is determined by:

• The mitotic count, which is the number of cells seen under a microscope that are in the process of splitting into two new cells (mitosis). 
• The Ki-67 index, which is a measure of the portion of cells that are almost ready to start splitting.

Based on these tests, NETs are divided into 2 main groups:

• Well-differentiated tumors (which include low-grade [G1] and intermediate-grade [G2] tumors) have 20 or fewer mitoses and a Ki-67 index of 20% or lower.
• Poorly differentiated tumors (high-grade [G3] tumors) have more than 20 mitoses or a Ki-67 index of more than 20%. These are also called neuroendocrine carcinomas (NECs), and they often grow and spread quickly.

Tumor functionality

The outlook for pancreatic NETs can be affected by whether the tumor is functioning (making hormones) or non-functioning. For functioning tumors, the type of hormone can also be important. For example, insulinomas (NETs that make insulin) tend to have a lower risk of spreading than other types of NETs.