Bladder Cancer Staging and Grading

Once the physician has determined that a tumor exists, the next step is to clarify the tumor's status. Several questions will have to be answered: Is the tumor large or small? Does it lie within the lining of the bladder or has it extended into the surrounding tissue? Has the tumor spread to nearby lymph nodes? Has the tumor metastasized to distant sites within the body?

Fortunately, a number of systems have been developed to answer these questions. The most common of these — the TNM (tumor, node, metastasis) system — allows tumors to be classified, or "staged," according to their overall characteristics. A biopsy is removed and sent to a histopathologist for examination under a microscope. The pathologist then assigns a stage and a grade to the tissue sample.

The stage refers to the physical location of the tumor within the bladder or, more specifically, the tumor's depth of penetration. In general, tumor stage is confined to one of two categories: (1) superficial, surface tumors, or (2) invasive, deep-spreading tumors. Superficial tumors affect only the bladder lining. They grow up and out from the lining tissue and extend into the bladder's hollow cavity. Invasive tumors grow down into the deeper layers of bladder tissue, and they may involve surrounding muscle, fat, and/or nearby organs. Invasive tumors are more dangerous than superficial tumors, since they are more likely to metastasize.

The grade is an estimate of the speed of tumor growth as suggested by cell features seen under a microscope. Most systems are based upon the degree of tumor cell anaplasia—that is, the loss of cellular "differentiation," the distinguishing characteristics of a cell. The World Health Organization (WHO) grading system groups transitional cell carcinomas (TCCs) into three grades that correspond to well-, moderately, and poorly differentiated cells. The International Union Against Cancer (UICC) has devised a four-grade system that considers Grade 1 tumors to be well-differentiated, Grade 2 to be moderately differentiated, and Grades 3 or 4 to be poorly differentiated. Both systems are widely used and can be summarized as follows:

  • Grade 1 (well-differentiated)
  • Grade 2 (moderately differentiated)
  • Grade 3 or Grade 4 (poorly differentiated)

There is a continuing debate about the classification of benign bladder lesions known as papillomas. The WHO defines papilloma as a single papillary (wart-like) growth with 8 or less cell layers in normal-looking surface tissue. By contrast, many pathologists and urologists classify papilloma as a Grade 1 TCC because of its tendency to recur and not to invade muscle.

There is a strong correlation between tumor stage and tumor grade. Nearly all superficial tumors are low grade; that is, they are Grade 1 tumors, with cells that are distinctly specialized and well-differentiated, whereas nearly all muscle-invasive tumors are high grade; that is, they are Grade 3 or 4 tumors, with cells that are nonspecialized and poorly differentiated. More importantly, there is a strong correlation between tumor stage and prognosis (the probable outcome of a disease), with superficial tumors having the most chance of a favorable result.

This TNM system for staging bladder cancer was developed by the UICC in 1997 (see Table 2).

Table 2: TNM Classification of Urinary Bladder Cancer

T - Tumor N - Regional Lymph Nodes M - Distant Metastasis
TX - Primary tumor cannot be evaluated T0 - No primary tumor
Ta - Noninvasive papillary carcinoma
TIS - Carcinoma in situ ("flat tumor")
T1 - Tumor invades connective tissue under the epithelium (surface layer)
T2 - Tumor invades muscle
    T2a - Superficial muscle affected (inner half)
    T2b - Deep muscle affected (outer half)
T3 - Tumor invades perivesical (around the bladder) fatty tissue
    T3a - microscopically
    T3b - macroscopically (e.g., visible tumor mass on the outer bladder tissue)
T4 - Tumor invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall
NX - Regional lymph nodes cannot be evaluated
N0 - No regional lymph node metastasis
N1 - Metastasis in a single lymph node < 2 cm in size
N2 - Metastasis in a single lymph node > 2 cm, but < 5 cm in size, or Multiple lymph nodes < 5 cm in size
N3 - Metastasis in a lymph node > 5 cm in size
MX - Distant metastasis cannot be evaluated
M0 - No distant metastasis
M1 - Distant metastasis

Publication Review By: Richard Levin, M.D., F.A.C.S., Stanley J. Swierzewski, III, M.D.

Published: 15 Jun 1998

Last Modified: 17 May 2011