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Bladder Cancer: Grading and Identifying each Stage

“Bladder cancer starts when cells that make up the urinary bladder start to grow out of control. As more cancer cells develop, they can form a tumor and, with time, spread to other parts of the body.

The bladder is a hollow organ in the lower pelvis. It has flexible, muscular walls that can stretch to hold urine and squeeze to send it out of the body. The bladder’s main job is to store urine. Urine is liquid waste made by the 2 kidneys and then carried to the bladder through 2 tubes called ureters. When you urinate, the muscles in the bladder contract, and urine is forced out of the bladder through a tube called the urethra.”1

“Cancer of the urinary bladder is the fourth most prevalent non-skin cancer in males in the USA, and ranks ninth in frequency among women. An estimated 61 420 new cases of bladder cancer were diagnosed in the USA in 2006. Tobacco smoking has been implicated in epidemiological studies as the cause of approximately 50% of bladder cancer cases in men and 30% in women. Various chemical and industrial exposures account for another 25% of these tumors in men and 11 % in women”2

Staging and grading cancer allows medical professionals to understand the different types, locations, and severity of bladder cancer. The “TNM” bladder staging system provides a framework and categorization for a disease (bladder cancer) that requires different strategies of treatment depending on its current state of progress by the way malignant cells look under a microscope. Staging describes where the cancer is located and whether it has spread (metastasized) to the surrounding tissues, organs or beyond. With this information, the doctor is in a good position to decide on the best treatment for the patient and the best possible outcome.

Bladder cancer staging is made after the examination of a biopsy removed through the urethra (a procedure called Trans-Urethral Resection of Bladder Tumor or TURBT). In addition to this, the patient is examined further to find out if the cancer has metastasized.

“Papillary tumors confined to the mucosa and invading the lamina propria are classified as stage Ta and T1, respectively, according to the Tumour, Node, Metastasis (TNM) classification system. Flat, high-grade tumors that are confined to the mucosa are classified as CIS (Tis). These tumors can be treated by transurethral resection of the bladder (TURB) and/or intravesical instillations and are therefore grouped under the heading of NMIBC for therapeutic purposes. However, molecular biology techniques and clinical experience have demonstrated the highly malignant potential of CIS and T1 lesions. The terms “NMIBC” and older one “superficial BC” are therefore suboptimal descriptions.”3

TNM bladder staging system

“A staging system is a standard way for the cancer care team to describe how far a cancer has spread. The staging system most often used for bladder cancer is the American Joint Committee on Cancer (AJCC) TNM system, which is based on 3 key pieces of information.”4

Doctors use various tests and radiological scans to come up with a comprehensive TNM staging which helps them answer the following questions:

  • (T) Tumor: what is the site of the primary tumor and how big is it?
  • (N) Node: which and how many lymph nodes are affected (if any)?
  • (M) Metastasis: to which parts of the body has the cancer spread to (if any) and to what extent?

The answers to these questions are considered together to come up with an individual’s staging results. Five stages of bladder cancer are recognized; they are:

  • Stage 0
  • Stages 1 to 4

“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, usually, after surgery, this information is combined in a process called stage grouping to assign an overall stage. The earliest stage cancers are called stage 0 (or carcinoma in situ), and then range from stages I (1) through IV (4).”5

TNM Classification of Urinary Bladder Cancer
TNM Classification of Urinary Bladder Cancer (6)

“While the TNM staging of bladder cancer guides both treatment and prognosis, there remains substantial heterogeneity among similarly staged patients, with respect to treatment response and overall outcomes. Therefore, there is a critical need for the identification of biomarkers to diagnose bladder cancer at an early stage, monitor recurrence, refine prognostic estimates, and predict response to treatment in patients with bladder cancer. Further, identification of such biomarkers is critical to refining our understanding of the pathogenesis of the disease, the biological basis for outcome disparities, and to informing more efficient treatment and surveillance strategies.”7

“Traditionally, bladder carcinomas have been graded according to the World Health Organization (WHO) 1973 grading of urothelial papilloma: well-differentiated (G1), moderately differentiated (G2), or poorly differentiated (G3). In 2004, the WHO and the International Society of Urological Pathology (ISUP) published a new grading system that employs specific cytologic and architectural criteria. The new WHO/ISUP classification differentiates between papillary urothelial neoplasms of low malignant potential (PUNLMP) and low-grade and high-grade urothelial carcinomas.”8

Types of Cancer Grading for Urothelial Papilloma (9)
Types of Cancer Grading for Urothelial Papilloma (9)

Grouping of Cancer Stages

Stage 0a

This occurs during the beginning of cancer, affecting the surface of the bladder’s inner lining. The underlying connective tissues and the muscles are not affected. This stage of bladder cancer is referred to as non-invasive papillary urothelial carcinoma. On the TNM staging system, it is Ta, N0, M0.

Stage 0is

Medically, this stage of bladder cancer is called flat/carcinoma in situ. The cancer is localized in the inner lining of the bladder without affecting bladder muscles, tissues or its hollow part. On the TNM staging system, it is Tis, N0, M0.

Stage 1

The bladder cancer has gone beyond the bladder lining into the lamina propria mucosae. The muscles of the bladder wall, lymph nodes or surrounding organs are not affected. The corresponding TNM staging system is T1, N0, M0.

Stage 2

Bladder cancer has invaded the bladder wall’s thick muscles. This stage is also known as invasive cancer or muscle-invasive cancer. The tumor, however, has not spread to the surrounding fat, lymph nodes or organs. The TNM staging system is T2, N0, M0.

Stage 3

The bladder cancer at this stage has metastasized beyond the bladder wall muscle to the fat layer and surrounding organs such as the prostate, the uterus or the vagina. The lymph nodes are, however, not affected. The TNM staging system for this is T4a, N0, M0.

Stage 4

This stage is determined by any of the following tumor states:

  • The tumor metastases have reached the pelvic or abdominal wall without invading the lymph nodes or other organs. This is T4b, N0, M0.
  • The tumor metastases have reached local lymph nodes but have not gone beyond that. This is T, N1-3, M0
  • The bladder cancer may or may not have metastasized to the lymph nodes but metastases have already reached various other organs. This is T, any N, M1.

“If cancer cells are found in the tissue sample from the bladder, a pathologist studies the sample under a microscope to learn the grade of the tumor. Tumors with higher grades tend to grow faster than those with lower grades. They are also more likely to spread. Your doctor uses this grade along with other factors to decide your treatment options.”10

“Grading describes how aggressive the cancer cells are:

  • Low grade – The cancer cells look fairly normal and behave similarly to healthy cells. The cells tend to grow slowly. Most bladder tumors are low grade.
  • High grade – The cancer cells look very abnormal and grow in a disorderly way. These cells tend to grow very quickly.

Bladder cancer can also be graded on a scale of 1–3. Grade 1 cancers are the slowest growing and grade 3 cancers are the most aggressive.”11

The staging and grading method help to categorize and define the different types of bladder cancers that manifest themselves in different stages. Armed with this ability to identify different cancers, physicians are better prepared to plan treatment and can attack the condition much more stealthily and adequately.

“Urothelial bladder cancer (UBC) is the fifth most common malignancy in Western nations. The typical diagnostic pathway relies on cystoscopy followed by transurethral resection to obtain histological confirmation of the tumor type, grade, and stage. Transurethral resection of bladder tumor (TURBT) is therefore both a diagnostic and staging procedure, as the specimen can be analyzed for depth of invasion.”12

“Historically, most of the data on the distribution of grade and stage of bladder cancer have been derived from retrospective studies on selected, often hospital- or clinic-based, patient populations. Such studies are likely to include a disproportionate number of patients with more aggressive or advanced-stage tumors. Only a small number of non-selected, population-based studies of bladder cancer have reported grade and stage data, primarily from Scandinavia”13



(1) About Bladder Cancer. The American Cancer Society medical. American Cancer Society. 2019.

(2, 13) Histological classification and stage of newly diagnosed bladder cancer in a population-based study from the Northeastern United States. Schned, A., Andrew, A., Marsit, C., Kelsey, K., Zens, M., & Karagas, M. Scandinavian Journal of Urology and Nephrology. 2008.

(3, 6, 9) Guidelines on Non-muscle-invasive Bladder Cancer (Ta, T1 and CIS). Babjuk, M., Böhle, A., Burger, M., Compérat, E., Kaasinen, E., Palou, J., Rouprêt, M., Van, Rhijn, B., Shariat, S., Sylvester, R., & Zigeuner, R. European Association of Urology. 2015.

(4, 5) Bladder Cancer Stages. The American Cancer Society medical. American Cancer Society. 2019.

(7) Biomarkers for bladder cancer management: present and future.Ye, F., Wang, L., Castillo- Martin, M., McBride, R., Galsky, M., Zhu, J., Boffetta, P., Zhang, D., & Cordon- Cardo, C. American Journal of Clinical and Experimental Urology. 2014.

(8) Epidemiology, Staging, Grading, and Risk Stratification of Bladder Cancer. Colombel, M., Soloway, M., Akaza, H., Böhle, A., Palou, J., Buckley, R., Lamm, D., Brausi, M., Witjes, A., & Persad, R. European Association Urology. 2008.

(10) Bladder Cancer Handbook. Cole, B., & Derossett, J. University of Michigan Rogel Cancer Center. 2014.

(11) Staging and prognosis of bladder cancer. Cancer Council. 2012.

(12) Prediction of histological stage based on cystoscopic appearances of newly diagnosed bladder tumours. During, V., Sole, G., Anderson, J., & Bryan, R. The annals of The Royal College of Surgeons of England. 2016.


María Laura Márquez
13 October, 2018

Written by

María Laura Márquez, general doctor graduated from The University of Oriente in 2018, Venezuela. My interests in the world of medicine and science, are focused on surgery and its breakthroughs. Nowadays I practice my more:

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