Bladder cancer (bladder or urinary bladder carcinoma) is a malignant tumor of the urinary bladder. Why bladder cancer develops is not yet exactly clear. One of the most important risk factors is smoking. In the early stages, it hardly causes any symptoms. The earlier bladder cancer is diagnosed, the better the chance of recovery. Read more about bladder cancer and bladder cancer BCG treatment here.
ICD codes for this disease: C68 | C67 | D09
• Symptoms: No specific symptoms, usually none at all for a long time, discoloration of the urine due to blood, disturbances in emptying the bladder such as frequent urination, pain when urinating.
• Course of the disease and prognosis: the earlier the diagnosis, the better the prognosis; if the bladder cancer is not in the muscle tissue, the chances of recovery are better, and depending on the stage, it can usually be treated with therapy.
• Causes and risk factors: The main risk factor is smoking, as well as contact with hazardous substances (eg at work), chronic cystitis, and certain medications.
• Diagnostics: Medical consultation, physical examination, urine examinations, cystoscopy, biopsy, imaging procedures such as computed tomography (CT), magnetic resonance imaging (MRT), X-rays.
• Treatment: Depending on the type of tumor and the stage: tumor removal via cystoscopy, open surgery, bladder instillations, chemotherapy and/or radiotherapy, immunotherapy possible and bladder cancer BCG treatment.
• Prevention: Refrain from smoking, no contact with hazardous substances (observe safety measures), consult a doctor early if you have bladder problems.
What is bladder cancer?
Bladder cancer (bladder carcinoma) is a malignant tumor of the wall of the urinary bladder. In the vast majority of cases, it originates from the mucous membrane of the bladder (urothelium). Doctors then speak of urothelial tumors.
Bladder cancer develops altered cells that divide faster than normal, healthy cells. If these altered cells spread to other organs and tissues, they may form secondary tumors (metastases) there.
Bladder cancer is the seventh most common type of cancer worldwide. Up to the age of 25, bladder cancer is very rare in both sexes and occurs with equal frequency. The risk of bladder cancer increases with age and more so in men. On average, men are 75 years old and women around 76 years old when the diagnosis is made.
The main risk factor for developing bladder cancer is smoking – it increases the risk of bladder cancer by two to six times compared to a non-smoker. Passive smoking is also dangerous. Tobacco use is believed to be responsible for about 50 percent of all bladder cancer cases.
How is bladder cancer manifested?
As with most malignant tumors, bladder cancer has no specific symptoms. For this reason, it is possible that behind the symptoms there is bladder cancer as well as many other diseases of the urinary tract.
Nevertheless, if you notice these bladder cancer symptoms, it is definitely advisable to consult a doctor.
The following symptoms sometimes indicate bladder cancer:
• Blood in the urine: The most common warning sign of a tumor in the bladder is a reddish to brown discoloration of the urine, not necessarily permanent and usually painless. This is caused by a small amount of blood in the urine. If this can be seen with the naked eye, the bladder cancer is usually at a more advanced stage than when the blood has not yet discolored the urine.
These blood admixtures are not a characteristic bladder cancer symptom, but occur in many urinary tract and kidney diseases. Often, most of those affected only seek medical attention when the urine is clearly bloody. Bladder cancer is usually well advanced by this point. For this reason, it is advisable to have this symptom clarified at an early stage.
• Frequent urge to urinate: Symptoms when urinating such as an increased urge to urinate with frequent emptying of only small amounts of urine (pollakiuria) require clarification. In some cases, they are an indication of a tumor in the bladder.
• Disorders of bladder emptying: Doctors call it dysuria. Urinating is difficult and often only works in small drops. Sometimes this is associated with pain. Many misinterpret these symptoms as cystitis.
• Pain: If there is pain in the flanks for no apparent reason, caution should be exercised, here it is necessary to consult a doctor. Because pain often only occurs in the advanced stages of bladder cancer. Then the bladder tumor already narrows the ureter or urethra.
• Inflammation: Chronic cystitis may indicate bladder cancer, especially if treatment with antibiotics is unsuccessful.
There are also general but rarer indications of bladder cancer, such as exhaustion or weight loss. Bladder cancer cannot be detected in the urine with the human sense of smell.
Is Bladder Cancer Curable?
The chance of recovery from bladder cancer depends on various factors. Also includes:
• How far has the tumor progressed? Is it superficial or does it emanate from deeper tissue structures? Has it spread to other structures or organs?
• Is it an aggressively growing bladder cancer?
• Are lymph nodes affected or are there already metastases?
Most bladder cancer patients are in an early stage at the time of diagnosis. The prospects of a cure are then favorable because the tumors at this stage relatively rarely form secondary tumors (metastases) and the cancer can usually be completely surgically removed.
As soon as bladder cancer penetrates into the muscle layer of the bladder (muscle-invasive tumors), the risk of metastasis increases. Because the muscle tissue is well supplied with blood and tumor cells reach other organs via the bloodstream. If bladder cancer has spread in this way, the prognosis is worse.
If the tumor cells have already grown beyond the urinary bladder or if there are distant metastases in the lungs, liver or skeleton, the chances of survival from bladder cancer decrease further. That’s why it’s important to get bladder cancer diagnosed and treated by a doctor as early as possible.
Because bladder cancer sometimes recurs after removal, regular follow-up appointments are necessary. In this way, possible recurrences (recurrences) can be recognized and treated in good time.
If left untreated, nothing will stop bladder cancer from spreading. Because of this, the malignant tumor, as it progresses, leads to metastases in the body and sooner or later to death.
What Causes Bladder Cancer?
In 90 percent of cases, bladder cancer originates in the urothelium. These are specific layers of tissue in the mucous membrane that line the bladder and other urinary tracts such as the ureter or tube. However, there are some factors that increase the risk of bladder cancer – often external influences.
Smoking: Main factor in bladder cancer
As with lung cancer, smoking is a significant risk factor for bladder cancer. The pollutants from cigarette smoke get into the blood, and the kidneys filter them out of the blood. They get into the bladder with the urine and develop their harmful effects there until the body excretes them again.
Doctors estimate that around 50 percent of all bladder cancers are caused by smoking. The risk of bladder cancer in smokers is two to six times higher than in non-smokers, depending on how long and how much you smoke. So if you stop smoking, you reduce the risk of bladder cancer.
Exposure to certain chemicals also increases the risk of bladder cancer. Aromatic amines, which are considered carcinogenic, are particularly dangerous. In the past, they were mainly used in the chemical industry, the rubber, textile and leather industries and in the painting trade.
In many cases, the disease is recognized as an occupational disease for people who handle these substances as part of their work and who develop bladder cancer.
This connection between chemicals and bladder cancer has been known for a long time. At the workplace, such chemicals are therefore only used under strict safety precautions. Sometimes they are even banned altogether. However, this is not the case in all countries.
Bladder cancer also develops very slowly—up to 40 years (latency period) can pass between exposure to the chemicals and the development of bladder cancer.
Therefore, it is possible for bladder cancer to occur in people who have worked with such chemicals a long time ago. In addition to the aromatic amines, there are other chemicals that may play a role in the development of bladder cancer.
Chronic bladder infections are also believed to be a risk factor for bladder cancer. Common bladder infections occur, for example, in people with a bladder catheter.
Drugs that increase bladder cancer risk
Cyclophosphamide, chlornaphazine, phenacetin and aristolochic acid are substances that have been shown to increase the risk of bladder cancer. Cyclophosphamide is a drug used in chemotherapy and is used, among other things, to treat leukemia, breast cancer and ovarian cancer.
Other infectious diseases
Some long-standing infectious diseases are associated with bladder cancer. An example is infection with schistosomes (pair flukes), which occur in the tropics and subtropics. They cause the disease schistosomiasis, which sometimes affects the bladder and urethra (urogenital schistosomiasis).
How is bladder cancer diagnosed?
Bladder cancer usually causes little or no symptoms. The bladder cancer symptoms are also so unspecific at the beginning that other diseases can also be considered.
However, if there is blood in the urine or persistent symptoms of bladder irritation, it is advisable to consult a doctor – preferably a family doctor or urologist. After all, the earlier bladder cancer is diagnosed, the better it can be treated.
The doctor will first ask you about your observations and symptoms (anamnesis). This includes, for example, information on the following aspects:
• Discoloration of the urine
• Problems urinating
• Increased urination
• Occupational exposure to chemicals
• Other existing diseases
After that, the doctor performs a physical exam . Only very large bladder tumors can be felt through the abdominal wall, rectum or vagina. He also examines a urine sample, which usually shows blood in the urine. In addition, a more precise laboratory examination of the urine for malignant cells (urine cytology) is carried out.
There are certain markers in the urine. Based on the determination of these markers, the doctor assesses whether bladder cancer is present or not. However, the results of these tests, which are also available as quick tests, have not yet been sufficiently accurate. For this reason, many doctors use them neither for diagnosis nor for early detection, since the result is not meaningful enough.
An abdominal ultrasound (sonography) can be used to assess the condition of the kidneys, renal pelvis, ureters and bladder and to identify whether there may be other causes of blood in the urine, such as urinary stones.
If the suspicion of bladder cancer is confirmed, the doctor usually suggests oneIf the suspicion of bladder cystoscopy. The patient is given a local anaesthetic, if necessary something to calm them down or a general anaesthetic.
During cystoscopy, the doctor inserts a special instrument (cystoscope) through the urethra, which allows the inside of the bladder to be examined. This examination enables the doctor to assess how deep the tumor has penetrated the mucous membrane of the bladder.
Bladder cancer can be diagnosed using a tissue sample (biopsy) from the suspected tissue. As part of a cystoscopy, the doctor removes the tissue sample using an electrosnare (transurethral electroresection of the bladder, TUR-B). Small, superficially growing tumors can sometimes be completely removed in this way. A pathologist then examines the cells under a microscope.
There are no tumor markers in the blood that are specific to bladder cancer. If the diagnosis of bladder cancer is confirmed, further examinations, primarily imaging, follow to determine the risk of the tumor spreading, how far the cancer has progressed and whether it has already spread to other organs.
• Ultrasound of the liver
• X-ray of the chest
• Computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen
• Bone scintigraphy in suspected bone metastases
How is bladder cancer treated?
As a rule, specialists from different disciplines work closely together in cancer therapy, for example surgeons, urologists, oncologists and psychologists. It is important that you are well informed about the cancer and the treatment options so that you can make the right decisions for you. Be sure to ask if you don’t understand something.
Bladder cancer therapy depends primarily on the stage of the disease. The tumor size, the location of the bladder tumor, how far it has spread, how malignant the tumor cells are and how fast the bladder cancer is growing are important. Doctors use these results to determine the exact stage of the disease (staging, staging). In this context, you create a kind of profile of the tumor (TNM classification), so to speak.
The treatment of bladder cancer usually depends on whether the tumor is in the muscle tissue or only superficial.
Endoscopic surgery (TUR) – removing the tumor
About 75 percent of those affected have a superficial tumor. This means that the bladder cancer is only in the bladder mucosa and has not yet reached the bladder muscles. Then it can be removed during the cystoscopy using the cystoscope. The surgeon removes the tumor in layers with an electric loop. An abdominal incision is not necessary here.
After the operation, a histological examination of the removed tissue is carried out. This makes it possible to determine whether it was possible to remove the tumor “when healthy”, i.e. completely.
Risk-dependent instillation treatment
In order to prevent bladder cancer from reoccurring in superficial tumors, patients with a medium and high risk in particular receive what is known as intravesical instillation treatment after the operation.
Doctors introduce a solution directly into the bladder via a bladder catheter. This solution usually stays there for a certain amount of time (usually two hours) and is then excreted when you empty your bladder. Depending on the risk, different solutions are used:
• Local chemotherapy after TUR: Immediately after the operation, patients receive preventive medicines against the cancer, so-called chemotherapeutic agents. The doctor flushes them directly into the bladder as part of the cystoscopy (intravesical chemotherapy).
• Local immunotherapy after TUR: In addition, doctors often use the tuberculosis vaccine Bacillus Calmette-Guérin (BCG) and also inject it directly into the bladder. The vaccine triggers an intense immune response in the body, which sometimes fights the tumor cells.
The medical follow-up treatment for bladder cancer usually lasts about six weeks on a weekly basis (induction phase). The treatment is on an outpatient basis and takes about two hours. The patients then go home.
In some cases, this induction phase is followed by a so-called maintenance phase, which lasts from several months to years.
Bladder Removal (Cystectomy)
In some patients, the bladder cancer has grown deeper into the wall and has already grown into the muscle. This requires a major surgical procedure in which the surgeons remove part or all of the bladder (cystectomy). This operation is performed either openly, with a laparoscope (abdominal endoscopy) or robot-assisted.
In addition, doctors remove the surrounding lymph nodes . This reduces the risk of the disease spreading again via possibly affected lymph nodes.
In men, the surgeons remove the prostate and seminal vesicles at the same time, and if there is a tumor in the urethra, these too. In women with advanced bladder cancer, the uterus, ovaries, part of the vaginal wall, and usually the urethra are removed.
If a complete removal of the urinary bladder is necessary, the doctor then creates an artificial urinary outlet through which the urine drains to the outside.
The simplest form is the implantation of the two ureters in a removed piece of small or large intestine about 15 centimeters long. Doctors guide the open end of this piece of intestine through the abdominal skin (ileum conduit). Since some urine always runs out of the abdominal opening with this form of urinary diversion, the person concerned always wears a urine bag.
Another option is to create a “new” bubble (Neobladder). Doctors form a collecting bag from a removed part of the intestine and connect it to the urethra. The prerequisite for this is that the transition from the bladder to the urethra was free of malignant cells in the histological examination. Otherwise it is necessary to remove the urethra as well.
The advantage of this variant is that urination is possible in the normal way. However, the patients do not have an urge to urinate. It is therefore necessary to empty the bladder at regular intervals by squeezing. Depending on fluid intake every three to four hours or at slightly longer intervals.
There is also the option of connecting both ureters from the renal pelvis to the last part of the colon (ureterosigmoidostomy). The urine then drains out during bowel movements.
Chemotherapy and immunotherapy
In addition to partial or complete removal of the bladder for bladder cancer that has already spread to deeper tissue (muscle), many of these patients receive chemotherapy before and after surgery. The aim of this is to improve survival time.
Sometimes it is not possible to remove the bladder or the patient refuses the procedure – chemotherapy, which affects the entire body and is intended to switch off tumor cells (systemic therapy), is also an option here.
Chemotherapy also helps with bladder cancer if the tumor is already very advanced (e.g. if it has spread to the lymph nodes in the abdominal cavity or to other organs). The therapy relieves the symptoms and has a life-prolonging effect.
For some patients who are not suitable for chemotherapy, doctors recommend the relatively new option of immunotherapy with so-called checkpoint inhibitors.
Bladder carcinoma is sensitive to radiation – the tumor cells can often be completely destroyed by radiation. Radiation treatment is an alternative to blister removal – this sometimes saves the blister.
Usually there is a combination of radiation and chemotherapy. The drugs used (cytostatics) make the tumor even more sensitive to radioactive rays. Doctors speak of radiochemotherapy. The irradiation often lasts several weeks and usually takes place daily for a few minutes.
Rehabilitation and aftercare
Follow-up treatment is necessary in many cases, especially for bladder cancer patients after a cystectomy and an alternative urinary diversion or with a neobladder. Here, those affected receive support in relation to urination, for example in the form of physiotherapy and training courses on artificial urinary outlets.
In addition, other topics are included in the advice and offers of help, such as lymphatic drainage and active movement therapy due to removed lymph nodes, psychological care and, especially for men, the addressing of possible sexual disorders after treatment.
It is also important that those affected attend regular follow-up appointments. This makes it possible for doctors to recognize early on whether the bladder cancer is coming back. But also to see whether there are any complications, how well the patient is doing with the therapy and whether there are any side effects. The frequency of the check-up appointments depends on the risk.
Intravesical therapy for bladder cancer
With intravesical therapy, your doctor puts liquid medicine directly into your bladder instead of giving it by mouth or injecting it into your blood. The medicine is given through a soft catheter that is placed into the bladder through the urethra. The medicine stays in the bladder for up to 2 hours. In this way, the drug can affect the cells lining the inside of your bladder without having major effects on other parts of the body.
When is intravesical therapy used?
After the TURB
Intravesical therapy is commonly used after transurethral resection of bladder tumor (TURBT). It is often done within 24 hours of the TURBT procedure. Some experts believe that it should be done within 6 hours. The goal is to destroy any cancer cells that may remain in the bladder.
To treat non-invasive bladder cancer
These cancers are only found in the lining of the bladder. They may be called noninvasive (stage 0) or minimally invasive (stage I) bladder cancers. These cancers have not spread deeper into the muscles of the bladder wall or to other parts of the body. Intravesical chemotherapy is used for these early-stage cancers, because drugs given this way mainly affect cells lining the inside of the bladder with little or no effect on cells elsewhere. This means that any cancer cells that are outside the bladder lining, including any that have grown deep into the bladder wall, are not treated with intravesical therapy.
One dose of intravesical chemotherapy may be the only treatment needed for noninvasive cancers.
Low-risk, noninvasive (low-grade) bladder cancers grow slowly. They can be treated with one dose of intravesical chemotherapy after TURBT. It is used to help keep the cancer from coming back.
Intravesical chemotherapy or immunotherapy may be used for intermediate noninvasive bladder cancers. Some studies suggest that immunotherapy is more effective. It is given once a week for 6 weeks, and can be repeated for another 6 weeks if needed. This is called induction therapy. After a break of 4 to 6 weeks, maintenance treatments are carried out for at least 1 year.
High-risk noninvasive bladder cancers may be fast-growing (high-grade), large, or there may be more than one tumor. These cancers are treated with intravesical induction immunotherapy. If there is a good response to induction therapy, maintenance intravesical immunotherapy is continued for 3 years.
Maintenance intravesical immunotherapy treatment schedules vary. For example, treatment can be done for 3 to 6 weeks every month, every 3 months, or twice a year. This treatment can be administered from 1 to 3 years. Your doctor will discuss with you the best plan based on the details of your bladder cancer and how it responds to treatment.
To treat more advanced invasive bladder cancers
One dose of intravesical chemotherapy is given within 24 hours of TURBT. However, other types of treatment are usually as follows for stage II to IV (2 to 4) bladder cancers, as these have spread outside the lining layer of the bladder wall.
Induction and maintenance intravesical immunotherapy is sometimes used after radiation therapy and systemic (blood) chemotherapy for stage II cancers if surgery cannot be done. It is rarely used for stage III. When used, it is used along with other treatments in cases where surgery cannot be done. Stage IV bladder cancers are rarely treated with intravesical therapy.
Types of intravesical therapy
There are two types of intravesical therapy:
Immunotherapy causes the body’s immune system to attack cancer cells.
Bladder cancer BCG treatment
Bladder cancer BCG treatment: Bacillus Calmette-Guérin (BCG) therapy is the most common intravesical immunotherapy for the treatment of early-stage bladder cancer. It is used to help keep the cancer from growing and to help keep it from coming back.
BCG is a germ that is related to the germ that causes tuberculosis (TB), but does not usually cause serious illness. It is administered directly into the bladder through a catheter. It reaches cancer cells and “activates” the immune system. Immune system cells are attracted to the bladder to attack cancer cells. BCG must come into contact with cancer cells to be effective. This is the reason it is used for intravesical therapy.
BCG treatment can cause a wide range of symptoms. Influenza (flu)-like symptoms such as fever, aches, chills, and fatigue are common and may last 2-3 days after treatment. It is also common to cause a burning sensation in the bladder, the need to urinate often, and even blood in the urine. Rarely, BCG can spread into the blood and throughout the body, causing a serious infection. This can happen even years after treatment. One sign of this may be a high fever that is not relieved by Tylenol or similar medications. If this happens, call your doctor right away. You may want to call your doctor’s office to ask about other serious side effects to watch for.
For this treatment, chemotherapy drugs (chemo) are put directly into the bladder through a catheter. These drugs actively kill growing cancer cells. Many of these same drugs can also be given systemically (usually through a vein) to treat more advanced stages of bladder cancer. Intravesical chemotherapy is most often used when intravesical immunotherapy is not working. It is rarely used for more than a year.
The chemotherapy solution may be heated before it is delivered into the bladder. Some experts think this makes the drug work better and helps it reach cancer cells. When the chemo is heated, it may be called hyperthermic intravesical therapy.
Mitomycin is the most commonly used drug for intravesical chemotherapy. Giving mitomycin into the bladder by heating the inside of the bladder, a treatment called mitomycin electromotive therapy , may work even better than giving mitomycin intravesically in the usual way.
Gemcitabine may cause fewer side effects than mitomycin and is less likely to be absorbed into the blood.
If BCG therapy stops working, valrubicin can be used, but not all experts agree with this treatment.
The main side effects of intravesical chemotherapy are irritation, a burning sensation in the bladder, and blood in the urine.
A main advantage of giving chemotherapy directly into the bladder instead of injecting it into the bloodstream is that the drugs usually don’t reach and affect other parts of the body. This helps people avoid many of the side effects associated with chemotherapy.
Can bladder cancer be prevented?
In order to prevent bladder cancer, it is particularly important to minimize both active and passive tobacco consumption. Ideally, you should give up smoking completely, as this reduces your risk of disease.
If you work in a profession that involves contact with hazardous substances, it is important that you observe safety regulations. Be aware that the time from exposure to hazardous substances to the onset of cancer may be very long (up to 40 years).
Don’t forget that there are no clear symptoms of bladder cancer and the disease usually does not cause any symptoms for a long time. If you suffer from chronic bladder infections, notice discoloration in the urine or suffer from bladder emptying disorders or pain, it is advisable to have this clarified by a doctor as soon as possible.