Bladder cancer

The function of the bladder

The urinary bladder (referred to as ‘the bladder’) is the organ that collects and stores urine produced by the kidneys (Fig. 1a & 1b). It is a hollow stretchy bag made of muscle tissue that sits on the pelvic floor muscles. The bladder expands as urine from the kidneys collects before being passed out of the body through the urethra (Fig 2.).

What is bladder cancer?

Bladder cancer is the growth of abnormal tissue (tumour) in the bladder. There are several stages of bladder cancer. Your treatment and experience will depend on the specific characteristics of the tumour (referred to as “staging” the tumour) and the expertise of your medical team.

This section provides general information about bladder cancer, diagnosis, and various treatment options. Discuss with your doctor what is best in your individual situation.

What causes bladder cancer?

Several biological factors and harmful substances can increase the risk of developing bladder cancer. A higher risk does not necessarily mean that someone gets cancer. Sometimes bladder cancer develops without any known cause.

Stages of the disease

A tumour that grows towards the centre cavity of the bladder without growing into the muscle tissue of the bladder is called non–muscle invasive. These tumours are superficial and represent an early stage. This is the most common type of bladder cancer. In most cases, these tumours are not aggressive and rarely spread to other organs, so they are not usually lethal, they can however appear again (=recurrence) or develop aggressive features (=progression)

As the cancer grows into the muscle of the bladder and spreads into the surrounding muscles, it becomes muscle- invasive bladder cancer. This type of cancer has a higher chance of spreading to other parts of the body (metastatic disease) and is harder to treat. In some cases, it may be fatal.

If bladder cancer spreads to other parts of the body such as the lymph nodes or other organs, it is called locally advanced or metastatic bladder cancer. At this stage, cure is unlikely, and treatment is limited to controlling the spread of the disease and reducing the symptoms.

Risk factors for bladder cancer

Bladder cancer develops slowly and is more common in older people (age 60 and older). According to the European Association of Urology’s bladder cancer guidelines, tobacco smoking contains many harmful substances and is responsible for almost half of the bladder cancer cases.

Another well-known source of risk is occupational exposure to chemicals used in the production of paint, dye, metal and petroleum, although workplace safety guidelines have helped reduce this risk.

Infections from certain parasites and chronic urinary tract infections increase risk of developing bladder cancer.

Bladder cancer prevention

A higher risk does not necessarily mean that someone gets cancer. Sometimes bladder cancer develops without any known cause.

It is important to maintain a healthy lifestyle. If you smoke, try to stop. Follow workplace safety rules and avoid exposure to harmful chemicals. Some evidence suggests that drinking a lot of fluids, mainly water, might lower bladder cancer risk. Eating a balanced diet with lots of fruits and vegetables has health benefits and might protect against cancer. If you have questions or need support to maintain a healthy lifestyle, ask your healthcare team for assistance or referrals.

Fig. 1a: The male lower urinary tract.
Fig. 1a: The male lower urinary tract.
Fig. 1b: The female lower urinary tract.
Fig. 1b: The female lower urinary tract.
Fig. 2: A healthy bladder.
Fig. 2: A healthy bladder.

Signs and symptoms

Blood in the urine is the most common symptom when a bladder tumour is present. Tumours in the bladder lining (non–muscle-invasive) do not cause bladder pain and usually do not present with lower urinary tract symptoms (urge to urinate, irritation).

If you have urinary tract symptoms such as painful urination or need to urinate more often, a malignant tumour might be suspected, particularly if an infection is ruled out or treated and this does not reduce the symptoms. Muscle-invasive bladder cancer can cause symptoms as it grows into the muscle of the bladder and spreads into the surrounding muscles.

Symptoms like pelvic pain, pain in the flank, weight loss, or the feeling of a mass in the lower abdomen may be present in some cases when tumours are more advanced.

Diagnosis

Your doctor will take a detailed medical history and ask questions about your symptoms. You can help your doctor by preparing for the consultation.

  • Make a list of your previous surgical procedures.
  • Make a list of the medications that you take.
  • Mention other diseases and allergies that you have.
  • Describe your lifestyle, including exercise, smoking,
    alcohol, and diet.
  • Describe your current symptoms.
  • Note how long you have had the current symptoms.

Urine test

Because blood in the urine is the most common symptom when a bladder tumour is present, your doctor will test your urine to look for cancer cells and to exclude other possibilities like urinary tract infections. Your doctor may refer to this test as ‘urinary cytology’.

Physical examination does not reveal non–muscle-invasive bladder cancer, and seldom reveals a mass if cancer has advanced to the muscle-invasive stage. If muscle-invasive bladder cancer is suspected, your doctor should perform rectal and, for women, vaginal examinations by hand (bimanual palpation).

In addition, your doctor will do a series of tests to make the diagnosis.

Urine biomarker tests for bladder cancer

Early detection of bladder cancer can improve the chance of successful treatment. Therefore, doctors try to find urine biomarker tests, which will help to identify bladder cancer or recurrence of bladder cancer as early as possible.

Cystoscopy

Cystoscopy is the main test used to diagnose bladder cancer. It allows your doctor to look at the inside of your bladder and urethra using a thin, lighted tube called a cystoscope.

CT urography

Computed tomography (CT scan) urography gives your doctor information about possible tumours in the kidneys or ureters and information about the lymph nodes and abdominal organs.

CT urography cannot detect small or superficial tumours (CIS). If small or superficial tumours are suspected further tests are needed.

MRI

Like CT scans, MRI scans show detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. MRI images are particularly useful in showing if the cancer has spread outside of the bladder into nearby tissues or lymph nodes.

Intravenous urography

Intravenous urography (IVU) is another imaging technique for examining the urinary tract. IVU may be used for the assessment of the upper urinary tract when CT-urography is not available. It cannot detect small or superficial tumours (CIS), and it’s not recommended for detecting lymph nodes or invasion of neighbouring organs.

Transabdominal ultrasound

Ultrasound is a non-invasive diagnostic tool that can visualize masses larger than 5-10mm in a full bladder. It cannot detect very small or superficial tumours (CIS). This study does not require intravenous contrast; however, ultrasound cannot replace CT urography or cystoscopy.

Transurethral resection of bladder tumour

TURBT is the surgical removal (resection) of bladder tumours. This procedure is both diagnosti c and therapeutic. It is diagnostic because the surgeon removes the tumour and all additional tissue necessary for examination under a microscope (histological assessment). TURBT is also therapeutic because complete removal of all visible tumours is the treatment for this cancer. Complete and correct TURBT is essential for good prognosis. In some cases, a second TURBT is required after several weeks.

Narrow-band imaging

Narrow-band imaging (NBI) is the application of light t specific blue and green wavelengths on the inner lining of the bladder during normal cystoscopy. This enhances the visual contrast
between healthy tissue and cancer tissue and improves the detection of tumours in the bladder. This method does not require any bladder instillation.

Classification

Bladder tumours are classified by tumour stage and subtype and by grade of aggressiveness of the tumour cells. Staging is a standard way to describe the extent of cancer spread. The kind of treatment you receive will depend on these elements.

Muscle- and non-muscle invasive bladder cancer

Metastatic disease

Prognostic factors and treatment decisions

If your bladder cancer has spread to another body organ (Fig. 1), treatment is unlikely to cure you. Treatment options are limited to controlling the spread of disease (metastasis) and reducing symptoms.

Fig. 3: Metastatic disease.
Fig. 3: Metastatic disease.

Treatment options for metastatic disease

Chemotherapy

In 90-95% of bladder cancer cases the histological type is urothelial carcinoma. Chemotherapy that contains platinum is the most effective treatment against this type of cancer.

Chemotherapy combinations like MVAC (which uses the drugs methotrexate, vinblastine, Adriamycin [doxorubicin], and cisplatin) or gemcitabine and cisplatin are prescribed most often. These treatments have side-effects that must be considered carefully if you cannot recover from your illness and the goal is to optimise your quality of life. Limited ability to perform daily activities (low performance status), other illnesses, or decreased kidney function could make you ineligible for these chemotherapies.

If you have reduced kidney function and cannot take the drug cisplatin, combinations like gemcitabine and carboplatin or M-CAVI (which uses the drugs methotrexate, carboplatin, and vinblastine) are slightly less effective options for treating bladder cancer.

Should your disease recur or progress while taking these therapies, treatment can be changed to another type of chemotherapy, but since there is no standard in this case, the choice will depend on your treating physician. Additional surgery to remove a metastatic or recurrent tumour mass is used only to relieve pain or obstruction and will not cure the disease. Radiotherapy can also be used to treat symptoms like pain or recurrent bleeding (haematuria).

Some types of chemotherapy are quite intensive and can have a lot of side-effects. If you are not fit or if you feel unwell from the cancer, these side-effects can be quite severe. Older patients in particular may benefit from less intensive types of chemotherapy.

Treatment of bone metastases

When bladder cancer has spread to the bone, skeletal complications can occur, such as weakening of the bones or pathological fractures from minor incidents or everyday activity. This causes pain and can have a detrimental effect on your quality of life. Your doctor may suggest radiotherapy, or drug treatment to help strengthen your bones and control the pain.

Access to clinical trials

All patients with a diagnosis of recurrent or metastatic bladder cancer, and particularly those whose prior chemotherapy has been unsuccessful, should be considered for centres where clinical trials are available.

A limited but increasing number of studies are available in various settings for patients who have never
had chemotherapy as well as pre-treated patients. In addition, the recent experimental use of drugs called ‘immune checkpoint inhibitors’ in advanced bladder cancer appears effective in a subset of patients with this disease.

Deciding on treatment

If treatment is intended to slow down the cancer and control the symptoms, deciding what treatment is best for you—or whether to have treatment at all— can be very difficult.

You will need a clear understanding of what drug treatment can do for you at this stage and how it will
affect your quality of life.

Talk to family or friends and people who are close to you. It can help to discuss things with someone
outside your inner circle. Your doctor may be able to refer you to a counsellor or specialist nurse.

Efforts are being made to promote patient advocacy for bladder cancer. Ask your oncologist if a bladder cancer patient representative is available near you.

Treatment of recurrence

Local recurrence

Local recurrence takes place in the soft tissue where the bladder has been before removal or at the site of the lymph nodes that were removed. This is due to the fact that even after removal of the local pelvic lymph nodes, some nodes are left in place. Most local recurrences appear within the first 2 years. Local recurrence after complete removal of the urinary bladder is associated with poor overall prognosis but can occasionally be treated (surgery, chemotherapy, targeted radiation therapy).

Distant recurrence

If the cancer recurs outside the pelvis, it is a distant recurrence. This type of recurrence is fairly common after bladder removal in patients with high risk of recurrence (larger tumours, positive resection margins, involvement of the removed lymph nodes). Distant recurrence happens mostly within the first 2 years after bladder removal. Sites of distant recurrences are lymph nodes, lungs, liver, and bones. Distant recurrence can be treated only by chemotherapy. Single or very few metastases may be surgically removed in addition to systemic treatment (= chemotherapy).

Medical trials might be available for your situation. Ask your doctor about these options.

FAQ – What is a positive resection margin?

Rim of tissue – called the surgical margin or margin of resection

The surgeon’s goal during surgery is to remove the cancer along with a rim of normal tissue around it. This is to ensure that all of the cancer has been removed.

During or after surgery, a pathologist examines this rim of tissue – called the surgical margin or margin of resection — to be sure it’s clear of any cancer cells. If cancer cells are present, this will influence decisions about treatments such as additional surgery and radiation.

Recurrence in the urothelial tract (urethra and ureters)

After complete removal of the bladder, the cancer can recur in the urethra, ureters and pyelum (urothelial tract). Most recurrences of the urothelial tract happen within the first 3 years after the operation. This type of recurrence is relatively rare.

If possible, a local treatment should be chosen to eliminate the cancer, unless systemic disease is suspected. In that case, chemotherapy or palliation should be used.

In case of bladder preserving therapy and a superficial (non–muscle-invasive) recurrence, washing the bladder with drugs to prevent the growth or spread of cancer cells (instillation therapy) is advised.

Risk factors for recurrence in the urethra after removal of the bladder:

  • Prior superficial (non–muscle-invasive) bladder cancer
  • Multiple bladder tumours
  • Tumour involvement of the bladder neck (and/or the prostate in men)
  • An unused/residual urethra after incontinent urinary diversion
  • Local recurrence in the lower pelvis

Although routine removal of the urethra (urethrectomy) is considered overtreatment, monitoring of the urethra is indicated in men.

Risk factors for recurrence in the ureters after removal of the bladder:

  • Prior superficial (non–muscle-invasive) bladder cancer
  • Multiple bladder tumours
  • Tumour involvement at the opening (orifice) of the ureter
  • Local recurrence in the pelvis

For patients with risk factors for urothelial recurrences, stringent or adapted monitoring is indicated.

Follow-up

After any kind of cancer treatment follow-up is essential to minimise complications and to detect and treat recurrences early. After complete removal of the bladder or other treatments, you will be asked to see your general practitioner, urologist, oncologist, radiologist, or a nurse practitioner at specific, fixed time intervals for monitoring and evaluation.

A specialist should have the lead in coordinating and interpreting all of the results from the follow-up visits. That specialist—in most countries, the urologist— should also be the main contact for questions about your disease or related issues.

Symptoms of complications

After monitoring of cancer, the functional results must be observed and controlled. Functional complications after bladder removal include vitamin B12 deficiency, high acid levels in the blood (metabolic acidosis), worsening kidney function, urinary infections, urinary stone formation, tightening of stoma openings (stricture), other stoma complications in patients with ileal conduit diversions (leakage, inversion, skin irritation), neobladder continence problems, and emptying dysfunction. Ask your doctor for information about the major symptoms of these complications and their prevention.

This information was last updated in March 2017.

It contains general information about bladder cancer. If you have any specific questions about an individual medical situation you should consult your doctor or other professional health care provider.

This information was produced by the European Association of Urology (EAU) Patient Information Working Group.

The content of this leaflet is in line with the EAU Guidelines on Bladder Cancer 2016.

Contributors:

  • Dr. Mark Behrendt, Amsterdam (NL)
  • Dr. Juan Luís Vasquez, Herlev (DK)
  • Ms. Sharon Holroyd, Halifax (UK)
  • Dr. Andrea Necchi, Milan (IT)
  • Dr. Evanguelos Xylinas, Paris (FR)