Bladder Cancer

Bladder cancer is a disease in which the cells lining the inner surface of the bladder, the flexible muscular sac responsible for storing the urine filtered by the kidneys, lose their genetic structure, multiply uncontrollably, and transform into malignant masses (tumors). This cellular deterioration, which begins when healthy epithelial cells lose their ability to undergo programmed death and divide rapidly, is initially confined only to the inner lining of the organ. However, the natural tendency of these malignant structures is to grow over time and infiltrate deeply into the protective muscular walls of the bladder and the surrounding connective tissues. This tumoral development, which directly targets our urinary storage system, is a critical cellular abnormality that must be stopped before it exceeds the anatomical boundaries of the organ.

What causes bladder cancer and in whom is it more common?

There is an extraordinary genetic control mechanism that enables the cells in our body to divide and multiply in a healthy manner. This mechanism ensures that damaged or aged cells are destroyed and replaced by new ones. However, when damage occurs in the DNA structure of the cells lining the inner surface of the bladder due to certain environmental or genetic factors, this control mechanism becomes disabled. The cells refuse to die and multiply rapidly, forming masses called tumors.

The most significant and proven environmental factor in the development of the disease is tobacco use. The moment a cigarette is smoked, thousands of carcinogenic substances in the smoke enter the bloodstream through the lungs. The kidneys, which are the body’s filtration system, filter these toxic chemicals from the blood and transfer them into the urine. By its nature, the bladder is a reservoir that holds urine for hours. During this waiting period, carcinogenic substances remain in prolonged contact with the inner lining of the bladder and begin to damage the genetic structure of the cells. Therefore, individuals who smoke have a many times higher risk of developing this disease compared with people who have never smoked in their lives. Moreover, even after smoking is stopped, it may take many years for the bladder cells to return to their former healthy state and for the risk to be completely eliminated.

Occupational exposure also has a major role that should not be overlooked in the development of the disease. Heavy chemicals used in certain branches of industry enter the body through respiration or the skin, reach the bladder through the kidneys, and cause damage there. This disease is much more common in individuals who have worked for many years without protective equipment in the dye, textile, tire, rubber, and petroleum industries. In addition, large stones that remain unnoticed in the bladder for years or untreated chronic infections may create continuous cellular irritation in the bladder wall and trigger the cancerous process over time. Radiotherapy treatments applied to the pelvic region in previous years or the use of certain powerful chemotherapy drugs may also disrupt the structure of the cells and create a basis for the formation of a new tumor years later. It is known that the disease is more common in advanced age and especially in men.

The main factors that increase the risk of the disease are as follows:

• Smoking
• Pipe
• Cigar
• Dye chemicals
• Petroleum products
• Textile dyes
• Rubber derivatives
• Pesticides
• Chronic bladder infections
• Bladder stones
• Pelvic radiotherapy
• Advanced age
• Male sex

What are the symptoms of bladder cancer and when should patients become suspicious?

The best-known and generally first symptom that directs patients to a physician is blood in the urine. However, this bleeding generally has a different character from bleeding caused by kidney stones or severe infections. Most of the time, it appears completely silently, without any pain, aching, or cramping. The color of the urine may suddenly turn pink, rust-colored, or dark red; sometimes clots may even be seen in the urine.

The greatest danger here is that this painless bleeding is not continuous. A person who passes bloody urine one day may produce completely normal and clear urine the next day. This creates the misconception in the patient that the problem has resolved on its own or was only related to temporary exposure to cold. However, the tumor continues to grow inside the bladder. Painless bleeding is the most important warning sign that must be taken seriously and requires detailed examination until proven otherwise. In some cases, the bleeding is too slight to be seen with the naked eye and is noticed only in microscopic urine tests performed during a routine health check-up.

Because the tumor occupies physical space on the inner surface of the bladder and irritates the tissue, certain changes also occur in patients’ daily urination habits. These symptoms, which exactly mimic a urinary tract infection, may cause patients to use antibiotics unnecessarily for a long time. The person may feel burning during urination and may experience a constant and urgent need to go to the toilet even though the bladder is not completely full. If no bacteria grow in urine culture tests and the complaints do not resolve despite antibiotic treatments, it should be considered that the underlying cause may be a flat tumor spread over the bladder surface.

When the disease reaches more advanced stages and crosses the boundaries of the bladder, spreading into the muscle tissue or surrounding organs, more systemic symptoms are added to the clinical picture. Obstruction of the urinary tract by the tumor may cause swelling in the kidneys and severe side pain. In addition, general health problems such as unexplained weakness and reduced body resistance begin to appear.

The clinical symptoms commonly encountered in this disease are as follows:

• Blood in the urine
• Clots in the urine
• Burning during urination
• Frequent urination
• Sudden urinary urgency
• Interrupted urination
• Side pain
• Back pain
• Pain in the pelvic region
• Unintentional weight loss
• Loss of appetite
• Chronic weakness

How is bladder cancer diagnosed and which tests are performed for diagnosis?

The diagnostic process of the disease progresses by listening to the patient’s complaints and then gradually applying a series of imaging and laboratory tests. The first step is generally ultrasonography, which does not tire the patient, does not involve radiation, and provides rapid results. The ultrasound device uses sound waves to display the inner wall of the urine-filled bladder on the screen. Polyp-like structures growing into the bladder or large masses can be easily detected by ultrasound. However, ultrasound may be insufficient in showing very small lesions, flat tumors, or how far the disease has progressed into the muscle layer.

At this point, contrast-enhanced computed tomography is used to see the condition of the kidneys, the urinary channels called ureters, and the lymph nodes in much greater detail. Thanks to the contrast agent administered intravenously, a complete map of the urinary tract is created. Tomography is an extremely critical imaging method for understanding whether the disease has extended beyond the bladder or caused any obstruction in the kidneys.

In addition to imaging methods, the laboratory test called urine cytology is also an important part of diagnosis. Cells shed from tumorous tissues into the urine are examined under a microscope in the pathology laboratory. This test is of great importance, especially in detecting flat tumor types called carcinoma in situ, which are difficult to see with the naked eye but are highly aggressive.

However, cystoscopy is the heart of diagnosis and the only indispensable method for establishing a definitive diagnosis. Cystoscopy is a direct observation procedure that cannot be replaced by any imaging device. During the procedure, a thin, flexible instrument with a small high-resolution camera and light source at its tip is inserted through the urinary tract, and the inside of the bladder is viewed on a screen as if examining a room. During this examination, the location, size, and shape of the tumor are seen clearly. Today, special blue-light filters are even added to cystoscopes to detect tumors so small that they might otherwise be overlooked. Thanks to these filters, tumor cells that are normally the same color as the bladder lining and remain hidden take on a glowing color in the dark and reveal themselves.

The main methods used during the diagnostic stage are as follows:

• Ultrasonography
• Computed tomography
• Magnetic resonance imaging
• Cystoscopy
• Blue-light cystoscopy
• Urinalysis
• Urine cytology
• Tissue biopsy

How is the surgical treatment of superficial (non-muscle-invasive) bladder cancer performed?

If a tumor is detected in the bladder as a result of the examination and imaging, the next step must be the surgical removal of this tissue. Cases in which the disease has not yet reached the main muscle layer of the bladder and remains limited only to the innermost surface lining or the soft tissue immediately beneath it are called superficial disease. The basic treatment at this stage is bladder tumor surgery performed with a minimally invasive method.

The procedure generally begins with numbing the patient from the waist down or putting the patient completely to sleep. The surgeon enters the bladder through the urinary tract with a special instrument. In the classical method, the tumor is scraped from its base and removed in small pieces with the help of an electrified wire loop at the tip of this instrument, and bleeding areas are sealed with heat energy. However, because this scraping and fragmentation process disrupts the integrity of the tumor, it may sometimes make it difficult for the pathologist to evaluate the depth of the disease fully and completely.

To overcome these difficulties and achieve much more flawless oncological clearance, a modern technique called en-bloc resection has been developed today. In this technique, the tumor is not scraped out piece by piece. Just as a plant in a garden is uprooted and removed in one piece together with the soil around its roots, the tumor is also separated from the bladder wall in one piece together with part of the healthy muscle tissue underneath it. Advanced laser systems or special cutting instruments are generally used for this procedure. The greatest advantage of this method is that it prevents tumor cells from dispersing into the bladder and provides the pathologist with an intact tissue specimen with which the stage of the disease can be determined without error.

In some cases, the patient may need to be taken back to the operating room a few weeks after the first surgery. If the removed tumor has a highly aggressive cellular structure, has extended into the layer beneath the surface, or no muscle tissue was seen among the specimens taken during the first operation, performing a second minimally invasive operation to remove diseased cells that may have remained at the microscopic level and to ensure the true depth of the disease is a standard and protective medical approach.

What intravesical treatments are applied after superficial bladder cancer surgery?

Even if the tumor has been completely removed through minimally invasive surgery, this disease naturally has a very strong tendency to recur and begin again from new foci. The inner surface of the bladder may have become genetically predisposed to tumor formation, or some cells released during surgery may attach to another corner of the bladder and begin to grow again. To minimize this risk, surgery alone is not considered sufficient, and liquid medications are administered directly into the bladder.

If the patient’s pathology result shows a low-risk tumor, a single dose of chemotherapy fluid is administered into the bladder through the urinary catheter on the day the surgery is completed. This fluid is kept inside the bladder for a certain period and then drained. This single-dose procedure significantly reduces the likelihood of recurrence by preventing free-floating cells from attaching to the tissue.

However, if the tumor is large, has appeared in multiple foci, or has an aggressive cell type, it is classified as intermediate or high risk. At this point, BCG, one of the most interesting and effective immunotherapies in medicine, is used instead of chemotherapy. BCG is actually the tuberculosis vaccine that has been known for years. Attenuated tuberculosis bacteria are converted into a liquid form in a laboratory and administered into the bladder with the help of a urinary catheter.

The purpose of this treatment is not for the bacteria to infect the patient; the aim is to deceive the immune system and draw it into the bladder. When the bacteria come into contact with the bladder wall, the body’s defense system believes that there is a serious infection there and gathers all its soldier cells in the bladder. An artificial, controlled, and very intense inflammatory battle begins inside the bladder. While the immune cells that flock to the area fight the bacteria, they simultaneously recognize and destroy microscopic cancer cells trying to hide in the bladder wall. This treatment generally begins a few weeks after surgery, when the tissues have healed. It is applied once a week for six weeks. Depending on the risk level of the disease, this treatment may be extended at monthly intervals for one year or even up to three years. Due to stimulation of the immune system, patients may experience temporary side effects such as frequent urination, burning in the urine, or mild fever on treatment days.

Which systemic and surgical treatments are applied in muscle-invasive bladder cancer?

When the abnormality in the cells begins at the surface and progresses over time to the main muscle wall of the bladder, the character of the disease changes completely. Cancer cells that reach the muscle layer gain access to the dense network of blood vessels and lymphatic channels located there. This significantly increases the likelihood of the tumor spreading outside the bladder to the lymph nodes, lungs, liver, or bones. At this point, scraping with a minimally invasive method or administering medication into the bladder is no longer sufficient to stop the disease.

The most effective and internationally accepted gold-standard treatment for disease that has progressed into the muscle layer is radical cystectomy, meaning the complete surgical removal of the bladder from the body. In this major operation, not only is the bladder removed. To completely block the pathways of disease spread, the prostate and seminal vesicles in men, and the uterus, ovaries, and part of the vagina in women, are removed together with the bladder as a single block. In addition, all lymph nodes in the region are meticulously cleared.

However, before entering the operating room, if the patient’s general health condition permits, applying systemic chemotherapy as a protective measure is one of the strongest recommendations of modern medicine. These powerful drugs, administered intravenously and circulating throughout the entire body, aim to eliminate microscopic spread that is too small to be detected even on radiological imaging. At the same time, they shrink the main tumor in the bladder, making the surgeon’s work easier and increasing the success rate of the operation. Because the drug Cisplatin, which is the cornerstone of this systemic treatment, may have exhausting effects on the body, whether the patient can tolerate this treatment is analyzed very carefully with various organ function tests.

The conditions the patient must have for this intensive treatment to be applied are as follows:

• Healthy kidney functions
• Adequate urine filtration capacity
• Intact hearing ability
• Normal cardiac contraction strength
• Undamaged nervous system
• Good liver values
• Strong bone marrow
• Adequate blood values

How is artificial bladder (Neobladder) surgery performed after advanced-stage bladder cancer surgery and who is it suitable for?

When the bladder is removed from the body, a new drainage system must be created so that the urine continuously produced by the kidneys can be safely expelled from the body. For this purpose, two different surgical approaches are generally followed. In the first option, a short segment of the small intestine is taken, the urinary tracts are connected to this bowel segment, and the other end of the bowel is brought to the abdominal wall. For the rest of the patient’s life, urine is removed from the body with the help of a special bag attached to the skin of the abdomen.

The second option is artificial bladder (neobladder) surgery, which is anatomically and psychologically the closest to the patient’s natural life. In this advanced operation, approximately half a meter of the patient’s own small intestine is cut and removed. The integrity of the digestive system is restored by suturing the remaining bowel ends together. This removed bowel segment is cut lengthwise and flattened to disrupt its natural tubular structure and reduce pressure. The bowel tissue is then folded again into a spherical shape using special suturing techniques and transformed into a new urine reservoir. The urinary channels coming from the kidneys are connected to this new reservoir, and the lower part of the reservoir is sutured to the patient’s natural urinary tract. In this way, the patient has the chance to urinate through the normal route by using the abdominal muscles without wearing any bag on the abdomen.

Unfortunately, this complex surgery cannot be performed in every patient. For the procedure to be successful, the characteristics of the tumor and the patient’s physiological condition must be examined very carefully.

The conditions in which artificial bladder surgery cannot be performed are as follows:

• Urethral tumor involvement
• Positive surgical margin
• Advanced age
• Cognitive impairment
• Learning difficulty
• Spinal cord damage
• Multiple sclerosis
• Severe pelvic nerve damage
• Inflammatory bowel diseases
• Crohn’s disease
• Ulcerative colitis
• Advanced heart failure
• Serious lung diseases
• Advanced kidney failure
• Liver failure

What are the possible risks of artificial bladder surgery and what is daily life like after bladder cancer surgery?

Adapting to the period after artificial bladder surgery is both a physical and psychological learning process for the patient. This is because the newly created reservoir is no longer made of a flexible bladder muscle but of bowel tissue capable of absorption. By its nature, the bowel tends to reabsorb certain minerals and acids from the urine into the blood. This may lead to an increased acid load in the blood and metabolic imbalances. To prevent this, patients may need to use alkaline medications at regular intervals.

In addition, bowel tissue is naturally programmed to produce a slimy fluid called mucus to help stool pass. This mucus production continues in the newly created bladder as well. Mucus accumulating in the urine may slow urinary flow or create sediment, laying the groundwork for stone formation. It is vitally important for patients to drink plenty of water every day to dilute mucus accumulation and overcome this problem.

The urinary continence mechanism is also one of the conditions that change after surgery. While holding urine is generally not a problem during the day thanks to control of the abdominal muscles, urinary leakage may occur at night because the muscles relax during sleep. Sometimes the opposite situation develops, and the patient cannot empty the urine completely because of narrowing at the urinary outlet. In this case, patients may need to empty their urine several times a day by themselves with the help of a clean catheter.

The possible problems that may accompany this complex surgery are as follows:

• Bleeding
• Urinary leakage
• Intestinal obstruction
• Metabolic acidosis
• Electrolyte imbalance
• Bladder stones
• Urinary tract infection
• Daytime urinary incontinence
• Nighttime urinary incontinence
• Inability to urinate
• Urinary tract narrowing
• Erectile dysfunction
• Vaginal dryness
• Deterioration in kidney functions
• Deep vein thrombosis

What should be considered to achieve complete success in bladder cancer treatment and to protect against the disease?

The fight against this disease does not end with successful surgery performed in the operating room; it requires lifelong discipline and follow-up. The complete and permanent cessation of tobacco and tobacco product use, one of the root causes of the disease, is the first and most important step of treatment. As long as carcinogenic substances continue to enter the body, no surgical or medication treatment can provide permanent long-term protection.

One of the most critical components of the treatment process is timing. Consulting a physician at the first moment a change in urine color or painless bleeding is noticed makes it possible to detect the disease while it is still on the bladder surface. The earlier the disease is detected, the higher the chance of preserving the bladder. The use of advanced imaging and light systems during the diagnostic stage allows even the smallest cellular abnormalities that might otherwise be overlooked to be detected and removed.

Full compliance with the intravesical immunotherapies planned by the physician after surgery is the strongest way to prevent the disease from silently recurring. When a decision is made to remove the bladder completely in people with advanced-stage disease, beginning preparations without losing time and not delaying surgery are of vital importance. Individuals continuing life with an artificial bladder or bag system must regulate their dietary habits, increase their daily fluid intake, and not neglect regular check-ups.

Frequently Asked Questions