Bladder cancer is a relatively common malignancy that develops in the bladder, a hollow, muscular sac in the pelvis that stores urine. The bladder is one of the main organs of the urinary system. 

The bladder is composed of four main tissue layers: the urothelium, lamina propria, muscularis propria, and perivesical tissue. The urothelium is the innermost layer of the bladder, and is made up of urothelial cells that prevent urine from being absorbed into the body. The next innermost layer of the bladder is the lamina propria, which contains the blood vessels surrounding the urothelium. The third layer of the bladder is the muscularis propria, which is the thickest, muscular layer. This layer is responsible for the contraction and dilation of the bladder, which is how we either hold or empty the bladder. The outermost layer is the perivesical tissue layer, which is made up of fat to separate and cushion the bladder from surrounding organs. 

Bladder cancer is more common in males, and is generally diagnosed over the age of 60. However, anyone can develop this disease.

Types of Bladder Cancer

There are several different types of bladder cancer, which are categorised by the types of cells they develop from, and whether or not the cancer has spread to the muscle in the bladder.

Non-Muscle-Invasive Bladder Cancer

Non-muscle-invasive bladder cancer (NMIBC) is bladder cancer that has not spread to the muscle layer of the bladder. This type of cancer is only found in the lining of the bladder, and is generally early-stage cancer. Any type of bladder cancer can be a NMIBC, and if left untreated it could become invasive. 

Muscle Invasive Bladder Cancer

Muscle invasive bladder cancer (MIBC) is bladder cancer that has spread to the muscle layer of the bladder. This type of cancer is often found in both the lining of the bladder, the muscle layer, and possibly further in advanced cases. This type of cancer can be seen as a late-stage cancer, and can be any type of bladder cancer.

Urothelial Carcinoma

Urothelial carcinomas, also known as transitional cell carcinomas, are the most common type of bladder cancer. They often develop from urothelial cells in the innermost layer of the bladder, or urothelium. While urothelial carcinomas can be aggressive, they can have a good prognosis.

Squamous Cell Carcinoma

Squamous cell carcinomas (SCCs) are a rarer form of bladder cancer that begin in the squamous cells that line the bladder.  They are more likely to develop as a result of chronic irritation of the bladder, such as an infection from long-term use of a urinary catheter, or chronic urinary tract infections. SCCs of the bladder are often aggressive, and may not have as good of a prognosis as other types of bladder cancer.

Adenocarcinoma

Adenocarcinomas of the bladder are a very rare subtype of bladder cancer that develop from mucus-producing cells, or glandular cells, in the lining of the bladder. Adenocarcinomas of the bladder are often aggressive, and may not have as good of a prognosis as other types of bladder cancer.

Rare types of Bladder Cancer

These types of bladder cancer are very rare:

• Sarcomas.
• Small Cell Carcinomas.
• Plasmacytoid carcinomas.
• Micropapillary carcinomas.

Treatment 

If bladder cancer is detected, it will be staged and graded based on size, metastasis (whether the cancer has spread to other parts of the body) and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you.

Cancers can be staged using the TNM staging system: 

• T (tumour) indicates the size and depth of the tumour. 
• N (nodes) indicates whether the cancer has spread to nearby lymph nodes. 
• M (metastasis) indicates whether the cancer has spread to other parts of the body. 

This system can also be used in combination with a numerical value, from stage 0-IV: 

• Stage 0: this stage describes cancer cells in the place of origin (or ‘in situ’) that have not spread to nearby tissue. 
• Stage I: cancer cells have begun to spread to nearby tissue. It is not deeply embedded into nearby tissue and had not spread to lymph nodes. This stage is also known as early-stage cancer.
• Stage II: cancer cells have grown deeper into nearby tissue. Lymph nodes may or may not be affected. This is also known as localised cancer. 
• Stage III: the cancer has become larger and has grown deeper into nearby tissue. Lymph nodes are generally affected at this stage. This is also known as localised cancer. 
• Stage IV: the cancer has spread to other tissues and organs in the body. This is also known as advanced or metastatic cancer.

Cancers can also be graded based on the rate of growth and how likely they are to spread: 

• Grade I: cancer cells present as slightly abnormal and are usually slow growing. This is also known as a low-grade tumour. 
• Grade II: cancer cells present as abnormal and grow faster than grade-I tumours. This is also known as an intermediate-grade tumour.  
• Grade III: cancer cells present as very abnormal and grow quickly. This is also known as a high-grade tumour.  

Once your tumour has been staged and graded, your doctor may recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.  

Treatment is dependent on several factors, including location, age, stage of disease, if the muscle is affected, and overall health.

Treatment of NMIBC

Treatment for NMIBC may include:

• Surgery, most often a transurethral resection of bladder tumour (TURBT).
• Chemotherapy.
• Immunotherapy. 
• Clinical trials.
• Palliative care.

Treatment of MIBC

Treatment of MIBC may include:

• Surgery, potentially including:
  • Partial cystectomy (partial removal of the bladder).
  • Total cystectomy (complete removal of the bladder).
  • Urinary diversions, such as a urostomy, neobladder, or continent urinary diversion.
• Chemotherapy.
• Radiation therapy. 
• Immunotherapy.
• Trimodal therapy (an alternative to a cystectomy that involves TURBT surgery, followed by a combination of radiation therapy and chemotherapy).
• Clinical trials.
• Palliative care. 

For more information on the treatment options, please refer to the Rare Cancers Australia treatment options page. 

Risk factors 

While the cause of bladder cancer remains unknown, the following factors may increase the likelihood of developing the disease:

• Having a history of smoking.
• Being male.
• Being over 60 years old.
• Being exposed to certain chemicals, potentially including:
  • Aromatic amines.
  • Benzene products.
  • Aniline dyes.
  • Arylamines.
  • Arsenic.
• Chronic irritation of the bladder, such as an infection from long-term use of a urinary catheter, or chronic urinary tract infections (generally only a risk for SCCs).
• Previous cancer treatment with either chemotherapy or radiation therapy.
• Certain treatments for diabetes.
• Having a history of cancer.
• Having a family history of bladder cancer.

Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.

Early symptoms 

The symptoms of a bladder cancer are generally the same across all subtypes, and may include:

• Blood in your urine (haematuria). 
• Burning feeling when you urinate.
• Increased frequency of urination.
• Increased urgency of urination.
• Constipation.
• Pain when urinating (dysuria). 
• Persistent urinary tract infections (UTIs).
• Unexplainable weight loss.
• Fatigue.
• Incontinence (involuntary loss of urine). 
• Abdominal pain (rare).

Not everyone with the symptoms above will have cancer but see your general practitioner (GP) if you are concerned. 

Diagnosis/diagnosing 

If your doctor suspects you have a bladder cancer, they may order the following tests to confirm the diagnosis and refer you to a specialist for treatment.

Physical Examination

Your doctor will collect your overall medical history, as well as your current symptoms. Following this, they may examine your body to check for any abnormalities. This may include a rectal examination, or a pelvic examination in females.

Pelvic Examination (Women)

The doctor will inspect the abdomen for any swelling or masses, followed by your genitalia. The doctor will then insert two fingers into your vagina while simultaneously pressing on your abdomen with their other hand to feel your uterus and ovaries. Following this, the doctor may use a device called a speculum into your vagina, which will separate the vaginal walls and allow viewing of your vaginal canal and cervix for any visible abnormalities. You many request a family member, friend, or nurse to be present during this exam.

Digital Rectal Examination (Males and Females)

A digital rectal examination (DRE) is an exam conducted by a urologist (a doctor specialising in issues pertaining to the kidneys, bladder, prostate, and male reproductive system). In this exam, the doctor will insert a finger (or ‘digit’) into your rectum to feel the area. If it feels hard or is an odd shape, further testing may be required.

Urine & Blood tests

Urine and blood tests are used to assess overall health and detect any abnormalities. Some of these tests may include:

• General blood test to assess overall health.
• Full blood count, which measure the levels of red blood cells, white blood cells and platelets.
• Blood chemistry and/or blood hormone studies, which analyse the levels of certain hormones and other substances in the blood.
• Urinalysis, which analyses the colour of your urine and its contents (e.g., sugar, protein, red and/or white blood cells etc.). 
• Urine cytology (collection of urine samples over a three-day period for analysis).

Imaging tests

The doctor will take images of your body using magnetic resonance imaging (MRI), a computed tomography scan (CT scan), radioisotope bone scan, pelvic ultrasound (including abdominal and trans-vaginal ultrasounds) and/or positron emission tomography (PET scan), depending on where it is suspected the cancer is. The doctor may also look at other parts of the body and looks for signs of metastasis.

Cystoscopy & Biopsy

A cystoscopy is a procedure that examines the bladder and urethra. A long, thin tube, with a light and a camera attached (cystoscope) is inserted through the urethral opening and into the bladder to determine if there are any abnormalities. This can be done under a local or general anaesthetic, and is often performed as a day procedure.

Once the location(s) of the cancer has been identified, the doctor will perform a biopsy to remove a section of tissue using a needle. The tissue sample will then be analysed for cancer cells.

Prognosis (Certain factors affect the prognosis and treatment options) 

While it is not possible to predict the exact course of the disease, your doctor may be able to give you a general idea based on the rate and depth of tumour growth, susceptibility to treatment, age, overall fitness, and medical history. Generally, early-stage bladder cancers have a better prognosis and survival rates. However, if the cancer is advanced and has spread, the prognosis may not be as good and there may be a higher risk of cancer recurrence. It is very important to discuss your individual circumstances with your doctor to better understand your prognosis.

References 

• Cancer Australia
• Cancer Council

^{Some references are to overseas websites. There may be references to drugs and clinical trials that are not available here in Australia.}