Gastrointestinal Stromal Tumor Stages and Other Prognostic Factors

After someone is diagnosed with cancer, doctors will try to figure out if it has spread, and if so, how far. This process, called staging, is based on the results of physical exams and other tests, which are described in Tests for Gastrointestinal Stromal Tumors.

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 for gastrointestinal stromal tumors (GIST) range from I (1) through IV (4). As a rule, the lower the number, the less the cancer has spread. A higher number, such as stage IV, means cancer has spread more. And within a stage, an earlier letter means a lower stage. 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.

The AJCC TNM staging system

The staging system most often used for GIST tumors is the American Joint Committee on Cancer (AJCC) TNM system; the most recent version is effective as of 2018. This staging system is based on 4 key pieces of information:

• The extent of the main (primary) tumor (T): How large is the cancer?
• The spread to nearby lymph nodes (N): Has the cancer spread to nearby lymph nodes? (This is uncommon in GISTs.)
• The spread (metastasis) to distant sites (M): Has the cancer spread to distant parts of the body? (The most common sites of spread are the liver, bones, lungs, and the tissue layers lining the inside of the abdomen.)
• The mitotic rate: This is a lab test measurement of how fast the cancer cells are growing and dividing. It is described as either low or high. A low mitotic rate predicts a better outcome.

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. Although the T, N, and M categories are the same for all GISTs, there are 2 different stage grouping schemes, depending on where the cancer starts:

• The stomach or the omentum (an apron-like layer of fatty tissue that hangs over the organs in the abdomen)
• The small intestine, esophagus, colon, rectum, or peritoneum (a layer of tissue that lines the organs and walls of the abdomen.)

This is because GISTs that start in the stomach or omentum are typically less likely to grow and spread to other parts of the body than GISTs starting in other locations.

Cancer staging can be complex, so ask your doctor to explain it to you in a way you understand.

GIST that starts in the stomach or the omentum

AJCC stage	TNM	Mitotic rate	Stage description* (2 cm = almost 1 inch; 5 cm = about 2 inches; 10 cm = about 4 inches)
IA	T1 or T2 N0 M0	Low	The tumor is: No more than 2 cm across (T1) OR Larger than 2 cm but not more than 5 cm across (T2). The cancer has not spread to nearby lymph nodes (N0) or to distant sites (M0). The mitotic rate is low.
IB	T3 N0 M0	Low	The tumor is larger than 5 cm but not more than 10 cm across (T3). The cancer has not spread to nearby lymph nodes (N0) or to distant sites (M0). The mitotic rate is low.
II	T1 N0 M0	High	The tumor is no more than 2 cm across (T1). The cancer has not spread to nearby lymph nodes (N0) or to distant sites (M0). The mitotic rate is high.
	OR
	T2 N0 M0	High	The tumor is larger than 2 cm, but not more than 5 cm across (T2). The cancer has not spread to nearby lymph nodes (N0) or to distant sites (M0). The mitotic rate is high.
	OR
	T4 N0 M0	Low	The tumor is larger than 10 cm across (T4). The cancer has not spread to nearby lymph nodes (N0) or to distant sites (M0). The mitotic rate is low.
IIIA	T3 N0 M0	High	The tumor is larger than 5 cm but not more than 10 cm across (T3). The cancer has not spread to nearby lymph nodes (N0) or to distant sites (M0). The mitotic rate is high.
IIIB	T4 N0 M0	High	The tumor is larger than 10 cm across (T4). The cancer has not spread to nearby lymph nodes (N0) or to distant sites (M0). The mitotic rate is high.
IV	Any T N1 M0	Any rate	The tumor is any size (Any T) AND it has spread to nearby lymph nodes (N1). The cancer has not spread to distant sites (M0). The mitotic rate can be low or high.
	OR
	Any T Any N M1	Any rate	The tumor is any size (Any T) AND 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 mitotic rate can be low or high.

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

• TX: Main (primary) tumor cannot be assessed due to lack of information.
• T0: No evidence of a main (primary) tumor.
• NX: Regional lymph nodes cannot be assessed due to lack of information.

GIST of the small intestine, esophagus, colon, rectum, or peritoneum

AJCC stage	TNM	Mitotic rate	Stage description* (2 cm = almost 1 inch; 5 cm = about 2 inches; 10 cm = about 4 inches)
I	T1 or T2 N0 M0	Low	The tumor is: No more than 2 cm across (T1) OR Larger than 2 cm but not more than 5 cm across (T2). The cancer has not spread to nearby lymph nodes (N0) or to distant sites (M0). The mitotic rate is low.
II	T3 N0 M0	Low	The tumor is larger than 5 cm but not more than 10 cm across (T3). The cancer has not spread to nearby lymph nodes (N0) or to distant sites (M0). The mitotic rate is low.
IIIA	T1 N0 M0	High	The tumor is no more than 2 cm across (T1). The cancer has not spread to nearby lymph nodes (N0) or to distant sites (M0). The mitotic rate is high.
	OR
	T4 N0 M0	Low	The tumor is larger than 10 cm across (T4). The cancer has not spread to nearby lymph nodes (N0) or to distant sites (M0). The mitotic rate is low.
IIIB	T2 N0 M0	High	The tumor is larger than 2 cm but not more than 5 cm across (T2). The cancer has not spread to nearby lymph nodes (N0) or to distant sites (M0). The mitotic rate is high.
	OR
	T3 N0 M0	High	The tumor is larger than 5 cm but not more than 10 cm across (T3). The cancer has not spread to nearby lymph nodes (N0) or to distant sites (M0). The mitotic rate is high.
	OR
	T4 N0 M0	High	The tumor is larger than 10 cm across (T4). The cancer has not spread to nearby lymph nodes (N0) or to distant sites (M0). The mitotic rate is high.
IV	Any T N1 M0	Any rate	The tumor is any size (Any T) AND it has spread to nearby lymph nodes (N1). The cancer has not spread to distant sites (M0). The mitotic rate can be low or high.
	OR
	Any T Any N M1	Any rate	The tumor is any size (Any T) AND 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 mitotic rate can be low or high.

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

• TX: Main (primary) tumor cannot be assessed due to lack of information.
• T0: No evidence of a main (primary) tumor.
• NX: Regional lymph nodes cannot be assessed due to lack of information.

The TNM staging system is not meant to be used for GISTs in children (pediatric GIST) or GISTS that are the result of inherited genetic syndromes. 

Resectable versus unresectable tumors

The AJCC staging system gives a detailed summary of how far a GIST has spread. But for treatment purposes, doctors are often more concerned about whether the tumor can be removed (resected) completely with surgery.

Whether or not a tumor is resectable depends on its size and location, if it has spread to other parts of the body, and if a person is healthy enough for surgery:

• Tumors that can clearly be removed without causing major health problems are defined as resectable.
• Tumors that can’t be removed completely (because they have spread or for other reasons) are described as unresectable.
• In some cases, doctors may describe a tumor as marginally resectable or borderline resectable if it’s not clear if it can be removed completely.

If a tumor is considered unresectable or marginally resectable when it is first found, treatments such as targeted therapy may be used first to try to shrink the tumor enough to make it resectable.

Other ways to determine treatment options and outlook

Along with the stage and resectability of the cancer, other factors can also affect treatment options and outlook (prognosis). 

For example, some GISTs are much more likely to grow and spread than others. Doctors are looking at ways to determine which tumors are potentially more dangerous (and therefore might need more aggressive treatment). Prediction tools have been developed to help with this. Doctors and patients can now get a reasonable idea of how likely a GIST is to grow and spread to other parts of the body, or to return (recur) after surgery, based on factors such as:

• Where the tumor starts
• The size of the tumor 
• The mitotic rate
• Whether or not the tumor has ruptured

Doctors are also looking at how mutations in the KIT or PDGFR2A genes, which often drive the growth of GIST cells, might affect how well the cancer responds to treatment with targeted therapy drugs. Testing for these mutations is now becoming more common.