Bladder cancer

Factsheet

Definition of bladder cancer

Cancer that starts in bladder cells. This guide focuses on cancer that emerges in the inner lining of the bladder, called transitional cell carcinoma. Other types of bladder cancer also exist but are not discussed here.

Diagnosis

  • Common symptoms of bladder cancer are urinary problems, blood in the urine, pain and urine blockage. However, these symptoms are not specific to bladder cancer and can also occur in many other conditions that are not related to cancer. To confirm the presence of bladder cancer, an examination called a cystoscopy is performed to inspect the interior of the bladder and the urethra for the presence of tumours.
  • There are specific tests that help with the diagnosis and evaluation of the dissemination of the disease. The diagnosis can only be confirmed through a histopathological examination in which samples of tissue from the tumour are examined in a laboratory. This reveals specific characteristics of the tumour and is used to determine the type of bladder cancer.

Treatment according to the extension of the disease (classified into stages)

  • Non-muscle invasive disease (stage 0a, stage 0is, stage I) involves a tumour confined to the mucosa (superficial layer of tissue in the lining of the bladder).
    • After cystoscopy all patients have the tumour removed by transurethral resection of bladder tumour (TURBT). This could eventually be curative if the complete tumour can be removed.
    • Sometimes adjuvant therapy can be administered, such as chemotherapy or immunotherapy instilled directly into the bladder, to avoid recurrence of the disease.
    • If these treatments fail, removal of the bladder (cystectomy) is an option.
  • Muscle invasive bladder cancer (stage II, stage III) involves a tumour that has invaded the muscle layer of the bladder or has extended through the bladder reaching the surrounding tissues.
    • The recommended treatment is radical removal of the bladder, including complete or partial removal of some surrounding organs. This process can be slightly modified to preserve organs as much as possible.
    • Chemotherapy or radiotherapy are recommended before surgery in order to improve the outcome. If a patient refuses surgery or if he/she is not fit enough to have it, radiotherapy alone, aggressive TURBT or TURBT combined with radiotherapy and/or chemotherapy are possibilities.
  • Advanced and metastatic disease (stage IV) involves a tumour that has grown through the bladder into the wall of the pelvis or the abdomen, or has spread to distant organs.
    • Chemotherapy is preferred as surgery, for this stage of disease, is unlikely to be curative. Surgery and radiotherapy after chemotherapy could be beneficial for selected patients.
    • Radiotherapy could also be useful to alleviate pain or bleeding.
  • Treatment of relapse:
    • Chemotherapy with the drug vinflunine plus best supportive care are indicated.
    • In case of failure, taxane- or platinum-based chemotherapy are proposed.
    • Patients are also encouraged to participate in clinical trials. 

Follow-up

Different tests may be performed during scheduled visits, depending on the staging and risk of recurrence. In non-muscle invasive cancer, these visits should take place every 3-6 months in the first 2 years and every 6 to 12 months thereafter (or as indicated by your medical team).

Introduction

Definition of bladder cancer

Bladder cancer is a cancer that forms in tissues of the bladder. The bladder is the organ that stores urine. The most frequent type of bladder cancer (90%) is transitional cell carcinoma. This type of cancer begins in cells that normally form the inner lining of the bladder, also called the transitional epithelium or urothelium. Other types of bladder cancer include squamous cell carcinoma, which begins in the thin, flat cells in the lining of the bladder, and adenocarcinoma, a cancer that begins in cells in the lining of the bladder that release mucus. Some other rare forms of bladder cancer also exist. This guide relates to transitional cell carcinoma.

 

Anatomy of the male (left) and female (right) urinary system showing the kidneys, ureters, bladder, and urethra. Urine is made in the renal tubules and collects in the renal pelvis. The urine flows from the kidneys through the ureters to the bladder. The urine is stored in the bladder until it leaves the body through the urethra.

 

GUIDE FOR PATIENTS BASED ON ESMO CLINICAL PRACTICE GUIDELINES
This guide for patients has been prepared by the Anticancer Fund as a service to patients, to help patients and their relatives better understand the nature of bladder cancer and appreciate the best treatment choices available according to the subtype of bladder cancer. We recommend that patients ask their doctors about what tests or types of treatments are needed for their type and stage of disease. The medical information described in this document is based on the clinical practice guidelines of the European Society for Medical Oncology (ESMO) for the management of bladder cancer. This guide for patients has been produced in collaboration with ESMO and is disseminated with the permission of ESMO. It has been written by a medical doctor and reviewed by two oncologists from ESMO including the lead author of the clinical practice guidelines for professionals. It has also been reviewed by patient representatives from ESMO’s Cancer Patient Working Group.

 

Frequency

Is bladder cancer frequent?

In 2012, it was estimated that approximately 151,297 patients were diagnosed with bladder cancer in Europe. Bladder cancer is the 5th most common cancer in Europe.

Bladder cancer is approximately five times more frequent in men than in women. It is estimated that 17.7 out of 100,000 men and 3.5 out of 100,000 women developed bladder cancer in 2012.  Of all cancers, bladder cancer is the 4th most common cancer in men, and the 13th most common cancer in women.

In the European Union, the likelihood for a man to develop bladder cancer at some point in his life lies between 1.5 and 2.5%. For men living in Flanders (Belgium), Malta, Spain and Italy this is somewhat higher: between 3.1 and 4.2%. For a woman in the European Union, the chances of developing bladder cancer at some point in her life are less than 1%.

The risk of developing bladder cancer increases with age: overall, 70% of patients who develop bladder cancer present symptoms after the age of 65.

 

Causes

What causes bladder cancer?

Currently, it is not entirely clear what causes bladder cancer. A number of risk factors have been identified, but in many cases none of these seem to be present. A risk factor increases the risk that a cancer may occur, but is neither necessary nor sufficient to cause cancer. A risk factor is not a cause in itself.
Some people with these risk factors will never develop bladder cancer and some people without any of these risk factors may nonetheless develop bladder cancer.

 

The main risk factors for bladder cancer are:

  • Aging: bladder cancer occurs most frequently in elderly people. Overall, 70% of patients developing bladder cancer are diagnosed after the age of 65.
  • Previous history of bladder cancer.
  • Cigarette smoking: cigarette smoking is the most important risk factor for bladder cancer. Stopping cigarette smoking for more than 4 years can lower the risk.
  • A number of chemicals have been identified that may cause bladder cancer:
    • Aniline dyes: chemicals that may be present in coloured fabrics.
    • Cyclophosphamide: a chemotherapeutic drug used for cancer treatment.
    • Aromatic amines: exposure to these chemicals can occur in various occupations such as those in the painting, leather, car, metal, paper and rubber industry, but also amongst truck drivers, dry cleaners, dental technicians and hairdressers. In these circumstances, bladder cancer does not occur until 30 to 50 years after exposure.
    • Arsenic: in a Taiwanese region where water contained high arsenic levels, an increased risk of bladder cancer has been found.
    • Aristolochia fangchi: this is a Chinese herb used in some dietary supplements and herbal remedies. An increased risk of bladder cancer was found in people that had used a dietary supplement in which this herb had been mistakenly added.
  • Irradiation: exposure to ionizing irradiation in the region of the bladder, for example during radiotherapy for prostate cancer, is thought to increase the risk of bladder cancer.
  • Some risk factors are particularly important for a specific type of bladder cancer, namely squamous cell carcinoma. This tumour is caused by chronic irritation or inflammation of the bladder. In Western countries, the main risk factors for squamous cell carcinoma include a badly-functioning bladder, prolonged presence of a catheter in the bladder, bladder stones and chronic bladder infection. In Africa and the Middle East, an important risk factor for squamous cell carcinoma is infection with Schistosoma hematobium, a microbe that is common in these regions. It can infect the bladder and lead to chronic inflammation.
  • Diabetes: individuals with type-2 diabetes have an increased risk of developing bladder cancer. 

Other factors have been suspected to be associated with an increased risk of bladder cancer, but the evidence is inconsistent:

  • Coffee, artificial sweeteners and alcohol: there is no clear evidence that consumption of these substances produces a risk for developing bladder cancer.
  • Tap water with high levels of trihalomethanes: these chemicals are the broken down products of the disinfectant chlorine. Some studies show that prolonged ingestion of this kind of tap water may increase the risk for bladder cancer, but the evidence is inconsistent.
  • Genes: overall, having a family member with bladder cancer conveys a slightly increased risk of developing the disease. Bladder cancer as a result of an inheritable faulty gene is very rare.
  • Body weight: one study has shown that being overweight is associated with a higher risk of bladder cancer, but other studies do not confirm this.

Some factors have been proposed to protect against the development of bladder cancer, but clear evidence for this is not available.

  • Fluid intake: it has been proposed that high fluid intake may reduce the risk of developing bladder cancer in men, but inconsistencies exist between studies.
  • Fruit and vegetables: consumption of fruit and vegetables is said to have a protective effect against bladder cancer.

 

Diagnosis

How is bladder cancer diagnosed?

Bladder cancer may be diagnosed during a routine physical check-up, or can be suspected on the basis of specific symptoms.

The main symptoms are:

  • Blood in the urine (called hematuria): this is usually painless and is experienced by 85% of bladder cancer patients.
  • Urinary problems: the need to urinate more frequently than usual (called frequency), the need to pass urine urgently (called urgency) or pain when passing urine (called dysuria).

However, these symptoms are not specific to bladder cancer and can also occur in many conditions that are not related to cancer, such as urinary infection, kidney stones or benign prostatic hyperplasia.
Bladder cancer may block the flow of urine from the kidney. Accumulation of urine within the kidney may lead to distension of the kidney (called hydronephrosis) and pain.

Besides asking about the symptoms mentioned above, the doctor will also perform a general physical examination and ask for laboratory blood tests to measure blood cell counts and kidney function.

The diagnosis of bladder cancer is based on the following examinations:

  1. Clinical examination

A physical examination provides information about signs of bladder cancer and other health problems. The doctor might examine the rectum and, in women, the vagina to determine the size of a bladder tumour and to see if and how far it has spread.

  1. Cystoscopy

A cystoscopy is a technical examination of the bladder: the doctor inserts a lighted tube with a camera at the end into the urethra to inspect the interior of the bladder and the urethra for the presence of tumours. Cystoscopy can be performed in the doctor’s office; with the use of a local anaesthetic gel, this procedure is usually well tolerated. However, cystoscopy may also be performed under general anaesthesia together with the clinical bimanual examination of the bladder.
The doctor can insert a fine surgical instrument into the cystoscope tube to remove – under direct vision - tissue samples from the tumour or from any other suspicious area. This specimen is called a biopsy. For certain bladder cancers, the doctor may immediately resect the entire tumour: this is called transurethral resection of the bladder tumour (TURBT). In this case, the cystoscopy also constitutes the first step in the treatment.
In specific circumstances, the doctor will also inspect the ureters, a procedure called ureteroscopy. In other circumstances, cystoscopy also includes biopsy sampling from the urethra.

  1. Urine cytology

This is a laboratory test performed to detect the presence of tumour cells in urine.

  1. Histopathological examination

This is the laboratory investigation of the tumour cells. It is performed on tissue removed from the tumour during cystoscopy. The histopathological information will confirm the diagnosis of bladder cancer and will reveal the specific characteristics of the tumour, allowing the doctor to determine the type of bladder cancer.
If surgery is indicated after the cystoscopy (usually a TURBT), a second histopathological examination will be performed on the tumour tissue obtained during surgery. This is very important to confirm the results of the first biopsy and to provide more accurate information on the cancer and the stage of the cancer.

  1. Radiological examination

If the histopathological examination shows that the tumour has grown into the deeper layers (the muscle layers) of the bladder, then radiological investigation is needed to determine if the tumour has also grown into the tissues and lymph nodes outside the bladder.
The radiological investigation is part of a diagnostic process called staging and can be performed using computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and pelvis. Since a synchronous upper tract urothelial tumour may exist in 2.5% of patients, upper urinary tract imaging with either CT urograms, or intravenous or retrograde pyelograms (special X-ray examination of the kidneys, bladder and ureters) should be undertaken. In patients with a high risk of metastases, additional tests may be performed, such as a CT of the chest, and also a bone scintigraphy if there are symptoms of tumour spread in the bones.

 

Treatment

What is it important to know to define the optimal treatment?

Doctors will need to consider many aspects of both the patient and the cancer in order to decide on the best treatment.

Relevant information about the patient
  • Gender
  • Personal medical history, previous illnesses and treatments
  • History of bladder cancer in relatives
  • General well-being and specific physical complaints
  • Results from the clinical examination
  • Results from laboratory tests on blood counts, kidney and liver function
Relevant information about the cancer
  • Staging

Doctors use staging to assess the extension of the cancer and the prognosis of the patient. The TNM staging system is commonly used. The combination of size of the tumour and invasion of nearby tissue (T), involvement of lymph nodes (N), and metastasis or spread of the cancer to other organs of the body (M) will classify the cancer as being at one of the stages described below.
The stage is fundamental in order to make the right decision about the treatment. The less advanced the stage, the better the prognosis. Staging is performed when the clinical and radiological investigations and the histopathological examination of the biopsy are completed. If surgery is indicated, a second staging will be performed on the basis of the laboratory examination of the surgical specimen.
The table below presents the different stages of bladder cancer. Since the definitions are somewhat technical, it is recommended to ask your doctor for a more detailed explanation.

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Layers of the bladder wall showing the mucosa (the bladder lining consisting of the epithelium and lamina propria) and the muscle layers.
 
  • Results of the biopsy

Tissue from the tumour biopsy is examined in a laboratory by a pathologist. This examination is called histopathology. If surgery is performed after cystoscopy, histopathological examination involves the examination of the tumour and the lymph nodes removed during surgery. This is very important to confirm the results of the initial findings and to provide more information on the stage of the cancer. The results of the examination of the biopsy include:

o Histological type

The histological type refers to the type of cells that compose the tumour. About 90% of bladder cancers are transitional cell carcinomas. This guide relates to transitional cell carcinoma, also called urothelial carcinoma, which is a tumour that arises from the transitional epithelium. The transitional epithelium consists of multiple layers of cells that can change shape as the bladder stretches and that line the innermost wall of the bladder.
The remaining 10% are predominantly squamous cell carcinomas and adenocarcinomas. Other histological types are very rare.

o Grade
The grade is determined on the basis of how different the tumour cells look from the cells normally found in a healthy bladder lining. The abnormal features indicate the rate at which the cells multiply and the degree to which they are invasive. There are four different grades of bladder cancer:

• Papilloma: a tumour composed of non-malignant cells.
• Papillary urothelial neoplasm of low malignant potential (PUNLMP): a tumour composed of non-malignant cells typically covered with a thickened layer of transitional epithelium.
• Urothelial carcinoma low grade: a malignant tumour that grows slowly and is unlikely to spread.
• Urothelial carcinoma high grade: a malignant tumour that grows faster and that is more likely to spread.


What are the treatment options?

Treatment planning involves a team of professionals from different medical disciplines. It usually involves a meeting of the different specialists, called a multidisciplinary meeting or tumour board review. In this meeting, the treatment planning will be discussed according to the relevant information mentioned above.

The treatment will usually combine therapies that:

The exact treatment will depend on the stage of the cancer, on the characteristics of the tumour and on the risks for the patient.

The treatments listed below have their benefits, their risks and their contraindications. It is recommended that patients ask their doctors about the expected benefits and risks of every treatment in order to be informed about the consequences of the treatment. For some treatments, several possibilities are available. The choice should be discussed according to the balance between benefits and risks.


Treatment plan for non-muscle invasive disease (stage 0a, stage 0is, stage I)

At these stages, the tumour is confined to the superficial layer of the bladder wall (mucosa) and does not invade the muscle of the bladder. The main goal of the treatment is to remove the local tumour by surgery during a TURBT. However, additional treatment delivered locally in the bladder (called adjuvant intravesical treatment) is recommended since it lowers the risk of the tumour recurring or progressing.
The type of adjuvant therapy used depends on the risk of progression and recurrence: for each patient with a stage 0a or stage I tumour, this is calculated using a scoring system based on several tumour-specific characteristics.

Cystoscopy and transurethral resection of the bladder tumor (TURB)

After an initial cystoscopy, all patients undergo a TURBT. Often, the complete tumour is resected, and, in this case, the TURBT is the definitive treatment. However, sometimes it is recommended to give additional treatment (called adjuvant treatment) with drugs that are applied directly into the bladder (called intravesical treatment). The type of additional treatment used depends on the individual risk of recurrence and progression, but also on the patient’s capability to tolerate the potential side effects associated with the treatment.
In selected patients with high risk tumours, a second TURBT is recommended either before or after intravesical therapy to detect any residual disease and to provide a more accurate staging.

Intravesical chemotherapy or immunotherapy

In order to reduce the risk of recurrence and progression, all patients that have had a TURBT are given one single intravesical instillation with a chemotherapeutic agent immediately after surgery. In most cases the drug used is Mitomycin C, but epirubicin or doxorubicin may also be used.
For patients with a tumour at low risk of recurrence and progression, one single instillation completes the treatment. For patients who are considered to have an intermediate or high risk of tumour recurrence or progression, the first instillation should be followed by further intravesical chemotherapy, or by intravesical immunotherapy with bacillus Calmette Guérin (BCG) (see below). Whether chemotherapy or immunotherapy is chosen depends on the individual risk profile. Chemotherapy is usually given for up to one year. Immunotherapy is given for a minimum of one year.

Intravesical immunotherapy with bacillus Calmette-Guérin (BCG)

For patients with certain risk profiles, it is recommended to give intravesical treatment with bacillus Calmette-Guérin (BCG), a vaccine used to protect against tuberculosis. The working mechanism of intravesical BCG therapy is not exactly understood. It is thought that BCG induces an immune reaction that kills cancer cells. Treatment with BCG is therefore considered as immunotherapy. Usually, an initial 6-week treatment regimen is given (called induction therapy), and this is followed by so-called maintenance therapy for a minimum of one year. Some maintenance regimens last two years.
Usually, an initial 6-week treatment regimen is given (called induction therapy), and this is followed by so-called maintenance therapy for a minimum of 1 year. Some maintenance regimens last two years.

Cystectomy

Cystectomy is recommended for patients with stage 0is and stage I tumours that do not respond to adjuvant intravesical treatment.


Treatment plan for muscle invasive bladder cancer (stage II, stage III)

At these stages, the tumour has invaded the muscle layer of the bladder or has extended through the bladder wall into the tissues surrounding the bladder. The treatment aims to surgically remove the entire bladder as well as the lymph nodes in the pelvis and the neighboring organs. Prior to surgery, chemotherapy is administered, with the aims of reducing tumour size, attacking tumour cells in metastases that are too small to be detected, and reducing the risk that tumour cells will spread to other parts of the body during surgery.


Radical cystectomy

The standard treatment for muscle invasive bladder cancer includes radical cystectomy. For male patients this involves the complete removal of the bladder, all visible tumour tissue, but also the urethra, prostate, seminal vesicles, the lower parts of the ureters and the lymph nodes in the pelvis. For female patients, radical cystectomy involves removal of the bladder, all visible and resectable tumours, the entire urethra, the lower part of the ureters, the adjacent vagina, the uterus and the lymph nodes in the pelvis.
In certain patients, this procedure may be slightly modified in order to preserve certain structures. Whether or not this is possible depends on the extent to which the tumour has spread and needs to be carefully evaluated in each individual patient.

Radical cystectomy leads to the loss of bladder function, that is, the storage of urine. The surgeon will therefore connect the ureters to a new outlet to allow evacuation of urine (called a urinary diversion). This new outlet may be either the urethra, the skin of the abdomen, or the very last part of the large bowel (called a rectosigmoid diversion). The choice of approach depends on many factors such as the tumour stage, the structures that can be preserved after radical cystectomy, the patient’s general medical condition and the patient’s preference. The different options are explained further in the text (see Side effects of therapies).
In addition, radical cystectomy may involve the removal of certain reproductive organs. This may lead to sexual dysfunction and/or the loss of reproductive function (see Side effects of Therapies).


Chemotherapy

It is recommended to give neo-adjuvant combination chemotherapy to patients with stage T2 or T3 disease. This means that a combination of chemotherapeutic drugs is given prior to cystectomy or definitive radiotherapy. The recommended combinations are gemcitabine and cisplatin (abbreviated GC), or methotrexate, vinblastine, doxorubicin and cisplatin (abbreviated MVAC). The purpose of neo-adjuvant therapy is to eradicate micrometastases, reduce tumour size and reduce the risk of tumour cells spreading during the surgical procedure.


Radiotherapy

Radiotherapy alone may be indicated for patients who are medically not fit enough to undergo the extensive surgery of radical cystectomy.
Radiotherapy may be given as part of a combination treatment in selected cases where the treatment aims to preserve the bladder (see: organ preservation therapy).


Organ preservation therapy

Organ preservation therapy refers to a treatment where the bladder is preserved. This is proposed to patients who do not wish to undergo radical cystectomy, or who are not medically fit enough to tolerate this kind of surgery. This treatment can be: aggressive TURBT, TURBT in combination with radiotherapy or chemotherapy, or TURBT in combination with radiotherapy and chemotherapy. The latter is called trimodality combination treatment and it is the preferred approach.
Organ preservation therapy may also be considered in selected patients with early stage bladder cancer, provided they meet a number of other stringent medical criteria.
Organ preservation therapy requires a stringent lifelong follow-up with cystoscopy and urine cytology to evaluate the response to treatment and to detect disease recurrence. If persistent or recurrent disease is observed, an immediate cystectomy is recommended, if possible.


Treatment plan for advanced and metastatic disease (stage IV)

At this stage, the tumour has grown through the bladder wall into the wall of the pelvis or the abdomen, or beyond the abdomen to distant organs. Since it is difficult or not medically indicated to remove the complete tumour by surgery, the primary goal of the treatment is to target tumour cells using chemotherapy that is given through a vein and that therefore acts systemically.

Chemotherapy

The standard combination regimen consists of the drugs cisplatin with gemcitabine (abbreviated as GC) or methotrexate, vinblastine, doxorubicin and cisplatin (abbreviated as MVAC). The MVAC regimen causes more toxic side effects than GC. Patients with limited advanced disease (lymph node involvement and no visceral metastasis in organs) and those who are medically fit may be able to receive high-dose MVAC in combination with granulocyte-colony stimulating factor (G-CSF), a growth factor that can increase tolerability of the chemotherapy.
Approximately half of patients are medically not fit enough to tolerate cisplatin due to poor general health, poor kidney function or the presence of other diseases. These patients are treated with carboplatin and gemcitabine (abbreviated CarboGem), with methotrexate, carboplatin and vinblastine (abbreviated M-CAVI) or with taxane or gemcitabine only. CarboGem is the reference treatment in this case. M-CAVI causes slightly more toxic effects than CarboGem.
The doctor evaluates the tolerability after each cycle of chemotherapy and evaluation of response to treatment is done after 2 to 3 cycles of chemotherapy by the same radiographic methods used to detect tumour lesions.

Surgery and radiotherapy after systemic chemotherapy

Systemic chemotherapy followed by cystectomy and lymphadenectomy or radiotherapy may be considered for selected patients with locally advanced disease.

Radiotherapy

Radiotherapy can be useful to alleviate pain or bleeding.

 

Treatment of relapse

So far, vinflunine plus best supportive care is recommended when the disease reappears after treatment with platinum-based chemotherapy for metastatic disease. Vinflunine as second-line chemotherapy is proposed when progression occurs less than 12 months after first-line treatment. In this case, taxane-based chemotherapy or participation in a clinical trial may also be proposed. If progression occurs later than 12 months after first-line treatment, platinum-based chemotherapy rechallenge may be considered.

 

Treatment of complications caused by disease

Blockade of urinary flow

Bladder cancer may block the flow of urine and cause urine to accumulate in the kidney. This may cause pain and disturbance of kidney function. If cystectomy is not possible because of advanced disease or because the patient is medically not fit enough to undergo this procedure, it may be necessary to divert urine flow away from the bladder to the exterior. This can be done by surgically connecting the kidney or the ureter to the skin of the abdomen. This is called nephrostomy and ureterostomy, respectively. The urine is collected in a plastic bag attached to the skin.

 

What are the possible side effects of the treatments?

 

Surgery

General risks and side effects

Some risks are common for every surgical intervention performed under general anesthesia. These complications are unusual and include formation of a blood clot in the veins, heart or breathing problems, bleeding, infection, or reactions to the anesthesia. These are largely prevented by thorough medical evaluation before surgery.

The bladder is located in the pelvis together with the local lymph nodes, parts of the bowel, major blood vessels, and the female reproductive organs. Depending on the extent of surgical resections needed to obtain the best results, some of these structures may become damaged. Accurate preoperative staging and imaging will help to minimize this risk.

When lymph nodes in the pelvis and the abdomen are removed, it can damage or block the lymph system resulting in lymphedema, a condition where lymph fluid accumulates in the legs and makes them swell. This may occur soon after the intervention, but also later.

Loss of bladder function after cystectomy

The consequence of cystectomy is that the function of the bladder is lost. Several surgical options exist to divert and collect the urine, either within or at the exterior of the body. The best choice needs to be carefully evaluated and will depend on the tumour stage, the surgical treatment given, the patient’s general condition, and the patient’s preference. The different possibilities are discussed briefly below. It is recommended to ask your doctor for more information.

Orthotopic neobladder. A new bladder organ (called a neobladder) is constructed: tissue from the bowel is used to form a pouch that is placed between the ureters and the urethra. Orthotopic means that the new bladder is in the same place as the original bladder. This pouch will store urine, and urine will be passed through the urethra.

Abdominal diversion. The surgeon connects the ureters to an artificial opening in the abdominal wall, called a stoma. This may be a direct connection or the surgeon may use tissue from the small intestine to guide the urine to the stoma. The urine is collected in a small plastic bag attached to the skin. The surgeon may also form a pouch on the inner side of the abdomen and a stoma that does not allow spontaneous passage of urine to the exterior: in this case the pouch can be emptied from the exterior using a catheter. This is called a continent urinary diversion.

Rectosigmoid diversion. The surgeon connects the ureters to the very last part of the large bowel, called the rectosigmoid. The rectosigmoid normally holds the stool and will now have the same function for urine. The surgeon may place a segment of intestine between the ureters and the rectosigmoid.

The nature and frequency of the side effects of these diversion procedures will depend on the type of procedure. The most frequent problems are narrowing of the ureter at the stoma and infection of the kidneys.
 

Sexual dysfunction and/or loss of reproductive function

Radical cystectomy in men includes the resection of the urethra, seminal vesicles and prostate. In women it includes the resection of the uterus and part of the vagina. The loss of these reproductive organs may lead to sexual dysfunction, the loss of the ability to conceive children, and in women it will lead to the loss of the ability to bear children. The doctor will refer such patients to specialized support providers.

Radiotherapy

Side effects of radiotherapy may occur in organs that are directly targeted, but also in healthy organs that lie close to the bladder and that cannot be avoided by the X-rays. For bladder cancer, modern radiation techniques are very safe and major complications occur in less than 5% of patients.
Effects on the urinary system include pain while passing urine, an urgent need to urinate, blood in the urine, blockage of urinary flow, and ulceration of the inner lining of the bladder.
Effects of radiation on the lower intestines include discomfort, diarrhea, mucus and blood discharge, and, rarely, perforation of the intestines.
In women, vaginal narrowing is a possible late effect of radiotherapy in the pelvic region.
The oncologist will advise on strategies to maximally prevent and relieve these reactions.

Intravesical instillation therapy

The main side effect of intravesical BCG instillation is inflammation of the bladder, called cystitis. The most severe side effect is a generalized infection, which may result when the bacilli are taken up through the bladder wall into the blood. Therefore, this therapy is not indicated in patients with reduced function of the immune system. In general, side-effects of intravesical BCG therapy can be managed.
Intravesical instillation of chemotherapy such as Mitomycin C may have several side effects, such as cystitis, allergy and skin reactions.

Chemotherapy

Side effects of chemotherapy are frequent but nowadays can be well controlled using adequate supportive measures. Side effects will depend on the drug(s) administered, on the dose and on factors specific to individual patients. If a patient has suffered from other medical problems in the past, some precautions should be taken and/or changes of the treatment should be made. Side effects are more severe when chemotherapy is given systemically (usually through a vein), than when it is given locally, directly into the bladder (see: intravesical drug therapy).

Listed below are the side effects that are known to occur with one or several of the chemotherapy drugs currently used for bladder cancer. The nature, frequency and severity of the side-effects vary for every combination used.

The most frequent side effects are:

  • Hair loss or hair thinning
  • Decreased blood cell counts, which may lead to anemia, bleeding and bruising, and infections
  • Tiredness
  • Feeling sick or being sick

Other side effects that may occur frequently with one or more of the chemotherapy drugs used for bladder cancer include:

  • Mouth sores or ulcers
  • Taste changes
  • Diarrhea
  • Gritty or watery eyes
  • Sensitivity to sunlight
  • Kidney damage
  • Hearing loss
  • Damage to the fetus in the womb of a cancer patient receiving chemotherapy
  • Loss of fertility
  • Interruption of periods in women (amenorrhea), which may be temporary

Occasional side effects include:

  • Changes in liver function
  • Damage to the heart muscle
  • Numbness or tingling in fingers and toes (peripheral neuropathy)
  • Constipation
  • Blurred vision
  • Skin rash or reddening of skin
  • Cough or shortness of breath
  • Liver changes
  • Changes in color of skin and/or nails
  • Allergic reaction
  • Inflammation around the drip/injection site
  • Fever and chills

Rare side effects are:

  • Depression
  • Sore eyes
  • Headaches
  • Increased heart rate
  • Dizziness
  • High blood pressure

Finally, it should be noted that some chemotherapy drugs can enter breast milk and may be harmful if passed to the baby.

 

What happens after treatment?

It is not unusual for cancer patients to experience treatment-related symptoms after the treatment has been completed.

  • Patients may experience anxiety, difficulty sleeping or depression, and may need psychological support.
  • During and after treatment, nutrition may become problematic due to reduced appetite, nausea and general malaise.
  • Difficulties in concentration and memory problems are not uncommon side effects of systemic chemotherapy, i.e. when administered in a vein or orally.
Follow-up with doctors

After completion of treatment the doctor will propose a follow-up aiming to:

  • Detect and prevent adverse effects of the treatment.
  • Detect possible recurrence as soon as possible and direct appropriate treatment.
  • Provide medical information, psychological support and referral to specialized support providers to optimize the return to normal daily life.

The follow-up protocol will include regularly timed office visits and investigations. The protocol depends on the grade and staging of the bladder tumour that was treated, and on the type of treatment given. In general, follow-up visits may include a combination of the following investigations:

  • History of general physical health and bladder cancer-related symptoms since the last visit
  • Cystoscopy to detect recurrence and to perform a biopsy of new lesions
  • Imaging of the upper urinary system
  • Urinary cytology: laboratory examination of the urine for the presence of tumour cells that are shed by a potentially recurring bladder tumour.
  • Laboratory investigations: blood chemistry and kidney function
  • Repeated radiological investigations in case initial examinations showed abnormal findings

There are no generally accepted follow-up protocols. The following are recommended possible regimens:

In non-muscle invasive bladder cancer, regular cystoscopy and urine cytology every 3–6 months during the first 2 years, based on the risk of recurrence, and every 6–12 months thereafter.
After definitive treatment of muscle invasive bladder cancer with radical cystectomy, urine cytology, liver function and renal function tests should be carried out every 3–6 months for 2 years, and subsequently as clinically indicated. Imaging of the chest, upper urinary tract, abdomen and pelvis should also be undertaken every 3–6 months for 2 years based on the risk of recurrence, and subsequently as clinically indicated.

For muscle invasive bladder cancer patients in whom an organ preservation strategy has been adopted, there is a need to evaluate response to treatment after induction chemoradiation. After completion, the same follow-up regimen as for patients with radical cystectomy is recommended. However, cystoscopy and urine cytology plus random biopsies every 3–6 months for 2 years are needed. During follow-up, monitoring of long-term treatment toxicities and potential recurrences of secondary tumours should be performed.

Returning to normal life

Returning to normal daily life may be difficult knowing that the cancer may come back. It is advised to eliminate any of the known risk factors for bladder cancer.
Follow-up visits with the doctor provide an opportunity for the patient to obtain medical information, psychological support and referral to specialized support providers. Additional expert psychological advice may be valuable, and some patients may find support in patient groups or patient-targeted information media. Dieticians may provide advice on adequate nutrition. Social workers may help in finding resources to ensure successful rehabilitation.


What if the cancer comes back?

If the cancer returns, it is called recurrence. The extent of the recurrence will direct the treatment decision, and this should be carefully determined for each individual patient.
In patients treated with organ preservation therapy, residual tumour can be detected in 20% of cases during restaging. An additional 20-30% of patients with initial complete responses will develop new or recurrent disease in the preserved bladder. Up to 70% of patients are free of tumours after the first cystoscopy control. A quarter of them develop a new lesion at a later time that requires additional treatment (cystectomy when possible).
For patients with metastatic disease who experience progression after completing a first-line platinum-containing regimen, a second-line chemotherapy regimen with vinflunine is recommended.

Synonyms

Bladder cancer

Bladder tumour

Bladder tumor

Cancer of the bladder

Tumour of the bladder

Tumor of the bladder

Cancer of the urinary bladder

Tumour of the urinary bladder

Tumor of the urinary bladder

Urinary bladder cancer

Urinary bladder tumour

Urinary bladder tumor

Transitional cell carcinoma of the bladder

Therapies by type

The following list of treatments is based on what we have found in scientific studies about cancer. More information about the listed therapies can be found under the tab THERAPIES. For registered drugs, radiotherapy and surgical interventions, approval by the authorities is given.

Surgical interventions

Procedures involving instrumental means to investigate or treat a cancer, or to improve the body’s functions or appearance. Generally, a surgical intervention involves an incision. More

Radiotherapy

Medical use of high-energy radiation to kill cancer cells and reduce tumor size. More

Registered drugs

Anti-cancer drugs with market authorization in the USA or in countries of the European Union. More

Synthetic products (excluding registered drugs)

Synthetically produced substances or modified natural products that are not registered as anti-cancer drugs.

Natural products (excluding registered drugs)

Substances found in nature that usually have a pharmacological or biological activity. More

Energy based therapies

Use of electromagnetic energy including electricity, magnetic fields, radio waves, microwaves, infrared rays and light to diagnose or treat disease.

Clinical trials

A clinical trial is a research study conducted with patients to evaluate whether a new treatment is safe (safety) and whether it works (efficacy). trials are performed to test the efficacy of drugs but also non-drug treatments such as radiotherapy or surgery and combinations of different treatments. Clinical trials take place in all kinds of hospitals and clinics, but mostly in academic hospitals. They are organized by researchers and doctors.

The Anticancer Fund provides a tool to search for phase III clinical trials by type of cancer and by country. For Belgium, the Netherlands, Switzerland, Luxembourg, France and the UK, the Anticancer Fund provides contacts to get more information about the phase III clinical trials currently ongoing. Discuss the possibilities of participating in one of these clinical trials with your doctor.

The list of the phase III clinical trials for bladder cancer is available here.