Bladder Cancer

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Staging

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.

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

According to recent consensus decisions of the American Joint Committee on Cancer (AJCC), the stage groupings of bladder cancers are as follows:

Individuals with Grade 1, Stage 0 tumors usually do not need any additional workup for staging, because there is little risk of metastasis. By contrast, individuals with more advanced tumors, for example, Grade 2, Stage 2 tumors, require a routine staging assessment. Such an assessment should include basic blood work, chest X-ray, lower body imaging by either computed tomography (CT scan) or magnetic resonance imaging, and a bone scan.

Ta (papillary, noninvasive carcinoma)

"Ta" tumors are papillary (wart-like) in nature. They often look like pink cabbages, and they may be present in groups. Ta tumors are confined to the inner surface of the bladder wall and are distinguished from T1 tumors because they have not broken through the basement (supporting) membrane.

TIS (carcinoma in situ; flat, pre-invasive tumor)

Carcinoma in situ (CIS) of the transitional epithelium — otherwise known as TIS — is very rare. In the past, TIS tumors were associated with high death rates because they often were undiagnosed. Unlike papillary tumors, TIS tumors are flat. The cancerous cells in TIS tumors are pre-invasive (confined to the basement membrane). When detected in the urine by Pap staining, TIS cells appear anaplastic (lacking cellular differentiation - the distinguishing characteristics of a cell). In middle-aged men, TIS may resemble cystitis without hematuria. Accurate diagnosis depends upon biopsy of the mucosa in any patients with unexplained cystitis or sterile pyuria (no microorganisms are present but there is "pus-like" matter in the urine).

T1 (tumor invasion of connective tissue)

During clinical inspection, T1 tumors often look like Ta tumors. These cancers may appear as an isolated mass, or they may be present in groups. But the distinctive feature of the T1 tumor is that—although it has broken through the basement membrane into the connective tissue of the bladder-lining mucous membrane (lamina propria)—the stalk of the tumor has not invaded the muscle below. Some physicians believe that T1 tumors should not be considered "superficial TCC," because they have the potential to be invasive and to progress. T1 tumors have a progression rate of roughly 30%. In T1 lesions of Grade 3 or Grade 4, nearly half of all tumors progress.

T2 (tumor invasion of muscle)

T2 tumors are characterized by the invasion of the muscle surrounding the bladder. If only the inner half of "superficial" muscle is affected (T2a tumor) and tumor cells are well-differentiated, the tumor may not have gained access to the lymphatic system. However, if the tumor has penetrated the outer half of "deep" muscle (T2b tumor) and cells are poorly differentiated, then the patient's prognosis usually is worse.

T3 (tumor invasion of perivesical tissue)

When a tumor has broken through the surrounding muscle and begins to invade the perivesical tissue (fatty tissue around the bladder) or peritoneum (membrane lining the abdominal cavity) outside of the bladder, it is classified as a T3 tumor. If the process of invasion has just begun and only can be seen by microscopy, then the tumor is classified as T3a. However, if the tumor is visibly massed on the outer bladder tissue, then it is classified as T3b.

T4 (tumor invasion of surrounding organs)

If a tumor has progressed to invade nearby organs—such as the prostate (a male gland that surrounds the bladder neck and urethra and adds a secretion to the semen), uterus (womb), vagina (female reproductive canal), or walls of the abdomen or pelvis (hip bone)—it is classified as T4. T4 tumors are, by and large, inoperable, meaning they can/should not be surgically removed. They may cause painful symptoms, hematuria, frequent urination, and sleeplessness. In addition, the necrotic (dead) tissue within the bladder often becomes infected. Surgery may be performed not as a cure, but as a method to reduce suffering in patients with T4 tumors.

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