Gallbladder Cancer Stages

After a person is diagnosed with gallbladder cancer, 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 earliest stage gallbladder cancers (called carcinoma in situ) are stage 0. Stages then range from stages 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.

Nearly all gallbladder cancers start in the epithelium (the inside wall of the gallbladder). Over time they grow through the various layers toward the outside of the gallbladder. They may also grow to fill up some or all the space inside the gallbladder at the same time.

How is the stage determined?

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

• The extent (size) of the tumor (T): How far has the cancer grown into the wall of the gallbladder? Has the cancer grown through the gallbladder wall into nearby organs such as the liver? 
  The gallbladder wall has several layers. From the inside out, these are:
  • The epithelium, a thin sheet of cells that line the inside wall of the gallbladder
  • The lamina propria, a thin layer of loose connective tissue (the epithelium plus the lamina propria form the mucosa)
  • The muscularis, a layer of muscular tissue that helps the gallbladder contract, squirting its bile into the bile duct
  • The perimuscular (around the muscle) fibrous tissue, another layer of connective tissue
  • The serosa, the outer covering of the gallbladder that comes from the peritoneum, which is the lining of the abdominal cavity

The depth that a tumor grows from the inside (epithelium layer) through the other outer layers (all the way through the serosa) is a key part of staging.

• The spread to nearby lymph nodes (N): Has the cancer spread to nearby lymph nodes and if so, how many?
• The spread (metastasis) to distant sites (M): Has the cancer spread to distant organs such as the liver, the peritoneum (the lining of the abdominal cavity), or the lungs?

The system described below is the most recent AJCC system, effective January 2018. This system is used to stage cancers of the gallbladder as well as cancers that start in the cystic duct (the tube that carries bile away from the gallbladder).

The gallbladder staging system uses the pathologic stage (also called the surgical stage) which is determined by examining the tissue removed during an operation. Sometimes, if surgery can't be done right away or at all, the cancer will be given a clinical stage instead. This is based on the results of a physical exam, biopsy, and imaging tests. The clinical stage will be used to help plan treatment. Sometimes, though, the cancer has spread further than the clinical stage estimates, and may not predict the patient’s outlook as accurately as a pathologic stage.

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 on this see Cancer Staging.

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

AJCC Stage	Stage grouping	Stage description*
0	Tis N0 M0	Cancer is only in the epithelium (the inner layer of the gallbladder) and has not grown into deeper layers of the gallbladder (Tis). It has not spread to nearby lymph nodes (N0) or to distant sites (M0).
I	T1 N0 M0	The tumor has grown into the lamina propria or the muscle layer (muscularis) (T1). It has not spread to nearby lymph nodes (N0) or to distant sites (M0).
IIA	T2a N0 M0	The cancer has grown through the muscle layer into the fibrous tissue on the side of the peritoneum (the lining of the abdominal cavity) (T2a). It has not spread to nearby lymph nodes (N0) or to distant sites (M0).
IIB	T2b N0 M0	The cancer has grown through the muscle layer into the fibrous tissue on the side of the liver, but has not invaded the liver (T2b). It has not spread to nearby lymph nodes (N0) or to distant sites (M0).
IIIA	T3 N0 M0	The cancer has grown through the serosa (the outermost covering of the gallbladder) and/or it has grown directly into the liver and/or one nearby structure like the stomach, duodenum (first part of the small intestine), colon, pancreas, or bile ducts outside the liver (T3). It has not spread to nearby lymph nodes (N0) or to distant sites (M0).
IIIB	T1-3 N1 M0	The cancer may or may not have grown outside of the gallbladder into the liver and/or one other nearby structure, but it has not grown into the main blood vessels leading into the liver (portal vein or hepatic artery) (T1 to T3). It has spread to no more than 3 nearby lymph nodes (N1). It has not spread to distant sites (M0).
IVA	T4 N0 or N1 M0	The tumor has grown into one of the main blood vessels leading into the liver (portal vein or hepatic artery) or it has grown into 2 or more structures outside of the liver (T4). It may or may not have spread to no more than 3 nearby lymph nodes (N0 or N1). It has not spread to distant sites (M0).
IVB	Any T N2 M0	The primary tumor may or may not have grown outside the gallbladder. The cancer has spread to 4 or more nearby lymph nodes (N2). It has not spread to distant sites (M0).
	OR
	Any T Any N M1	The primary tumor may or may not have grown outside the gallbladder. The cancer may or may not have spread to nearby lymph nodes. It has spread to distant sites such as the liver, peritoneum (the lining of the abdomen [belly]), or the lungs (M1).

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

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

Other prognostic factors

Besides your stage, there are other factors that can affect your prognosis (outlook).

Grade

The grade describes how closely the cancer cells look like normal gallbladder cells when seen with a microscope.

The scale used for grading gallbladder cancer is from 1 to 3.

• Grade 1 (G1) means the cancer cells look a lot like normal gallbladder cells.
• Grade 3 (G3) means the cancer cells looks very abnormal.
• Grade 2 (G2) falls somewhere in between.

Low-grade cancers (G1) tend to grow and spread more slowly than high-grade (G3) cancers. Most of the time, the outlook is better for Grade 1 and Grade 2 cancers than it is for Grade 3 cancers of the same stage for gallbladder cancer.

Subtype

The specific type of gallbladder cancer you have can influence your outlook. Rare cancer types such as squamous and adenosquamous carcinomas of the gallbladder tend to have a worse prognosis (outlook) than adenocarcinomas (the most common type) and papillary carcinomas.

Lymphovascular Invasion

If cancer cells are seen in small blood vessels (vascular) or lymph vessels (lymphatics) under the microscope, it's called lymphovascular invasion. When cancer is growing in these vessels, there's a greater chance that it has spread outside the gallbladder. Gallbladder cancers with lymphovascular invasion tend to have a poor prognosis.

Extent of Resection

If the entire gallbladder tumor can be removed with surgery, it can impact the overall outlook. Cancers that can be removed completely by surgery tend to have a better outlook than those that cannot. 

• Resectable cancers are those that doctors believe can be removed completely by surgery.
• Unresectable cancers have spread too far or are in too difficult a place to be removed entirely by surgery.

Only a small percentage of gallbladder cancers are resectable when they're first found.