Bladder Cancer Stages

Cancer staging refers to the measurement of the size of a cancer and how far it has spread. Physical examination, diagnostic imaging (e.g., ultrasound, x-ray, CT scan, MRI scan), and microscopic examination of tissue biopsies are commonly used to determine a cancer’s stage. Staging is important as it guides treatment selection and gives an indication of a patient’s likely clinical outcome (i.e., their prognosis).

As different classification systems may be used for staging, the terminology to describe a bladder cancer’s stage may vary. In this article we describe the approaches used for staging urothelial carcinoma, which constitutes approximately 90% of all bladder cancers,¹ and explain some of the terms that may be encountered by patients and their families during diagnosis and treatment.

The ‘TNM’ staging system

The TNM system is commonly used to stage bladder cancers. It is made up of three components:

• T (= tumor) describes the size of the primary tumor and where it is located. The term primary tumor is used to refer to the tumor that develops first.
• Assigned as category Ta, Tis, T1, T2, T3, or T4 – see below for an explanation of these tumor categories.
• N (= node) indicates whether the cancer has spread to nearby lymph nodes and, if so, the location and number of nodes it has reached. Lymph nodes are small, bean-like structures that are part of the immune system; nearby lymph nodes are also called ‘regional’ lymph nodes.
• Assigned as category N0 (no nearby lymph node involvement), N1, N2, or N3 (reflecting increasing amounts of spread to nearby lymph nodes)
• M (= metastasis) denotes spread to distant organs such as the lungs or liver and/or to lymph nodes outside the pelvis (called ‘distant’ lymph nodes).
• Assigned as category M0 (no metastasis) or M1 (metastasis)

Further details of TNM staging classifications for bladder cancer may be found at the website of the American Society of Clinical Oncology.

Location of bladder cancer tumors

The bladder wall is made up of several layers. From innermost to outermost these are:

1. The urothelium lining (i.e., the lining of the urinary tract);
2. The connective tissue underlying the urothelium (sometimes referred to as the ‘submucosa’);
3. The muscle layer; and
4. The fatty tissue surrounding the bladder within the pelvis.

Non-muscle invasive bladder cancer refers to tumors within the bladder wall that do not extend into the muscle layer. They may be in the urothelium only or may have spread into the connective tissue that underlies it.

• Non-muscle invasive cancers that have not spread beyond the urothelium are sometimes referred to as ‘superficial’ tumors. The two main types are:
• Non-invasive papillary carcinoma (category Ta): small, finger-like growths that project from the lining of the bladder towards the hollow center. Over time these tumors can grow into the bladder wall and spread to other parts of the body.
• Non-invasive carcinoma in situ (category Tis): a flat tumor that may appear as a red, velvet-like area on the bladder lining. This type of tumor has a high likelihood of progressing to invasive bladder cancer.
• Non-muscle invasive cancers that have spread into the connective tissue underlying the urothelium but have not penetrated the muscle layer are referred to as category T1 tumors.

Muscle invasive bladder cancer refers to tumors that have spread into or through the muscle layer of the bladder wall. Depending on the extent of their spread these tumors are assigned to one of the following categories:

• T2: a tumor that has spread into the muscle layer.
• T3: a tumor has spread through the muscle layer and into the fatty tissue surrounding the bladder.
• T4: a tumor that has spread to nearby pelvic organs (T4a) or the pelvic or abdominal wall (T4b).

Metastatic bladder cancer refers to tumors that have spread to distant organs or lymph nodes outside the pelvis. Metastatic bladder cancer may also be referred to as advanced bladder cancer. The TNM staging system assigns metastatic cancers as ‘M1’.

• Metastatic bladder cancers are usually preceded by muscle-invasive bladder tumors (i.e., T2, T3, and T4). This is because once cancer cells reach the muscle layer of the bladder wall it becomes easier for them to spread into other parts of the body.
• Although non-muscle invasive bladder cancers (i.e., Ta, Tis, and T1) can metastasize, this is relatively rare.
• Almost any organ can be involved in a bladder cancer metastasis, but the most common sites are distant lymph nodes, bones, lungs, and liver.

Bladder cancer stage groupings

TNM stages can be grouped to provide a simplified, standard description of the cancer that enables the medical team to clearly communicate and plan treatment. In general terms, these stage groupings are:

• Stage 0: Refers to tumors that have not spread beyond the bladder’s urothelium lining. These tumors are either papillary carcinoma (Ta) or carcinoma in situ (Tis), as described above. 
• Stage 1: Refers to tumors that have reached the connective tissue underlying the urothelium but not penetrated the muscle layer of the bladder wall (i.e., T1 tumors), or spread to lymph nodes or other organs. 
• Stage 2: Refers to tumors that have grown into the muscle layer of the bladder wall but not penetrated the fatty tissue surrounding the bladder (i.e., T2 tumors), or spread to lymph nodes or other organs. 
• Stage 3: Describes bladder cancers that have spread to the fatty layer surrounding the bladder and/or to organs and lymph nodes within the pelvic cavity (primary tumor may be T1–T4a), but have not spread to the pelvic or abdominal wall, distant organs, or lymph nodes outside the pelvis. 
• Stage 4: Describes bladder cancers that have spread to the wall of the pelvis or abdomen, or that have metastasized to distant organs or lymph nodes outside the pelvis (primary tumor may be any T category). 

What does the grade of a bladder cancer refer to?

Cancer grade refers to the appearance of the tumor cells when examined under a microscope.

• Low grade tumor cells are similar in appearance to normal cells and usually grow slowly. In general, bladder tumors made up of low grade cells tend to stay within the urothelium.
• High grade tumor cells have a very abnormal appearance and tend to grow quickly and spread to deeper layers of the bladder wall. Tumors made up of high grade cells often recur after treatment.
• Although considered superficial because they are located initially in the bladder lining, carcinoma in situ tumors are high grade. Compared to papillary carcinomas, they are more likely to lead to invasive bladder cancer and have a higher rate of recurrence.

Why is the staging and grading of bladder cancer important?

Accurate staging and grading of bladder cancer is important as it helps to determine a patient’s most appropriate treatment pathway and provides an indication of their prognosis.
For example, the treatment for non-muscle invasive tumors is usually different to that for muscle invasive tumors:

• Non-muscle invasive bladder cancers are usually treated with TURBT (‘transurethral resection of bladder tumor‘) surgery to remove the tumor(s), which may be combined with medicine delivered directly into the bladder (referred to as ‘intravesical‘ therapy).
• Muscle-invasive bladder cancers may require treatment that uses a combination of surgery, systemic therapy (administered by injection or taken orally), and radiation therapy. 
• Visit our Bladder Cancer Treatment page for further information regarding treatments for bladder cancer.

A patient’s prognosis refers to the predicted outcome of their bladder cancer. Several factors contribute to prognosis, including bladder cancer type, stage and grade, response to treatment, and the individual’s characteristics (e.g., age, medical history).

How successful is bladder cancer treatment?

Bladder cancer can usually be treated effectively, especially when tumors are diagnosed at an early stage. Bladder cancers detected at late stages are often more complex to treat and may have an uncertain prognosis. Subsequently, the statistical 5-year relative survival rate (i.e., the percentage of patients who would be expected to survive the effects of their bladder cancer for 5 years or more) is high for bladder cancers that are still within the surface layer of the bladder wall (96%) or have not spread beyond the bladder (69%), and progressively lower for cancers that have spread within the pelvis or to distant sites.² See Bladder Cancer Survival: The Importance of Early Detection for further information related to the factors affecting bladder cancer survival.

Bladder Cancer Detection

Several tests and procedures, including non-invasive genomic urine tests like Cxbladder, are available to determine whether an individual has bladder cancer or to establish an alternative diagnosis. Some of these clarify the presence of symptoms (such as haematuria) and others identify alternative causes of these symptoms (such as an infection). Importantly, these tests and procedures are used in combination to determine an overall diagnosis.
Learn more about bladder cancer detection

Last Updated: 22 Oct 2024 06:45 am

• References
  1. American Society of Clinical Oncology (ASCO). Bladder Cancer: Introduction. Accessed August 10, 2021.
  2. American Cancer Society. Survival Rates for Bladder Cancer. Accessed August 8, 2021.

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