Bladder Cancer

Understanding Staging and Grading

Bladder cancer is classified according to the tumor, node and metastasis (TNM) system developed by the American Joint Committee on Cancer (AJCC). Doctors categorize the tumor (T) according to its depth of invasion, whether cancer cells are found in nearby lymph nodes (N), and whether it has metastasized (M), or spread, to other parts of the body. Once the cancer is classified, an overall stage is assigned (see Tables 1 and 2).

Bladder tumors are given a clinical stage based on the results of a physical examination, evaluation of biopsy specimens and the results of imaging studies and CT scans. A pathologic stage is then based on more invasive testing, including surgery, to accurately establish how far the disease has spread. If cancer spreads beyond the bladder, your doctor may recommend biomarker testing to check for genetic mutations, which may also inform treatment.

Urothelial cancer is also described by grade (G) (see Table 3). The grade indicates how likely the cancer is to recur, grow or spread.

Identifying Mutations

Diagnosing bladder cancer and determining the best treatment for your type may include genomic testing, which is performed on a sample of tumor tissue. It is used to examine a cancer’s genes to identify mutations that could indicate the cancer’s behavior, aggressiveness and whether it will metastasize.

In bladder cancer, genomic testing is increasingly being used to determine whether the tumor has certain targetable characteristics that would indicate which type of treatment may be most effective. If a mutation is found, your doctor will select a drug therapy that may target that specific mutation. However, not all mutations have approved treatments available.

Multiple gene mutations that contribute to bladder cancer have been discovered, and research is ongoing to find additional mutations that may affect the treatment or prognosis (outlook) of bladder cancer. Some of the common gene mutations found in bladder cancer include the following: ATM/RB1 , ERCC2 , FGFR2 , FGFR3 , HER2 , HRAS , PIK3CA , TP53 and TSC1 , among others. If the testing does not identify a specialized treatment, standard of care and clinical trials will be the options to consider.

Research has also identified some chromosome abnormalities that may play a role in bladder cancer. These abnormalities include variations in the number and structure of certain chromosomes. Partial or complete loss of chromosome 9 has been found to be associated with recurrence of low-grade bladder cancer. In addition, abnormal numbers of chromosomes 3, 7, 13 and 17 have been found in some bladder cancers.

Illustrated Stages of Bladder Cancer

Table 1. AJCC system for bladder cancer

Category Definition
Tumor (T)
TX Primary tumor cannot be assessed 
T0 There is no evidence of primary tumor
Ta A papillary carcinoma is detected but is considered to be noninvasive
Tis There is evidence of a noninvasive flat carcinoma (flat carcinoma in situ, or CIS)
The tumor has grown from the inner lining of the bladder to the connective tissue, but hasn't yet spread to the muscle layer of the bladder
The tumor has invaded the muscle layer of the bladder
The tumor has grown into only the inner half of the muscle layer
The tumor has grown into the outer half of the muscle layer

The tumor has grown through the muscle into the fatty tissue (also known as the perivesicle fat or serosa)
Invasion of the tumor to the serosa can be seen only through a microscope
Invasion of the tumor to the serosa can be felt by the surgeon or seen on imaging tests
The tumor has spread beyond the bladder and may be growing into surrounding organs, seminal vesicles and the pelvic and abdominal wall
The tumor has spread to the prostate in me or to the uterus and/or vagina in women
The tumor has spread to the pelvic wall or abdominal wall
Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 Cancer has not spread to regional lymph nodes
N1 Cancer has spread to one pelvic lymph node
N2 Cancer has spread to two or more pelvic lymph nodes
N3 Cancer has spread to lymph nodes along the common iliac artery
Metastasis (M)
M0 Cancer has not spread to distant areas of the body
Cancer has spread to distant areas of the body (most commonly to distant lymph nodes, bones, the lungs and/or the liver)

Table 2. Stages of bladder cancer

Stage TNM Classifications
0a Ta N0 M0
0is Tis N0 M0
I T1 N0 M0
II T2a or T2b N0 M0
III T3a, T3b or T4a N0 M0
IV Tb4
Any T
Any T
N1, N2 or N3
Any N

Table 3. Grades of bladder cancer

Classification Definition
Urothelial Histologies
LG Low-grade.
HG High-grade.
Squamous Cell Carcinoma and Adenocarcinoma
GX Grade cannot be assessed.
G1 Well differentiated.
G2 Moderately differentiated.
G3 Poorly differentiated.