All About Bladder Cancer

Everything You Need To Know About Bladder Cancer

The urinary bladder is a hollow muscular sac in the pelvis just above and behind the pelvic bone. It has flexible and muscular walls that stretch to contain urine and squeeze it to send it out of the body. Urine is liquid waste made by the pair of kidneys, which is then carried to the bladder by channels called ureters. Urination happens when the muscles in the bladder contract. Urine passes out of the bladder through a tube called the urethra. This article focuses on the types of and treatment options available for bladder cancer.

What is bladder cancer

Bladder cancer occurs when the cells of the bladder begin to grow uncontrollably. As the number of cells increases, they form a tumor and eventually spread to other parts of the body. 

The causes are not definite, but genetic history, genetic mutations due to the use of tobacco or exposure to chemicals are important risk factors. Moreover, smokers are more likely to develop bladder cancer than nonsmokers. Other risk factors are:

  • Bladder defects at birth
  • Side-effects of chemotherapy and radiation therapy
  • Chronic bladder infections and irritations
  • Exposure to chemicals, including aromatic amines and arsenic in water
  • Low fluid consumption
  • Family genetic history of bladder cancer
  • Being male and white
bladder cancer

Signs and Symptoms of Bladder Cancer

What are Urinary Bladder Cancer Signs And Symptoms?

The most common symptoms that bladder cancer manifests are urinary issues. Blood in the urine is one of the first. It may be orange, pink or dark red.The following symptoms may imply that one needs an immediate check up:

  • When the urine changes color / mixed with blood
  • Urge to urinate more frequently than usual, but not being able to urinate
  • Urinating more frequently than usual
  • When it hurts or burns while urinating

While these symptoms are likely to be caused by urinary tract infection (UTI), bladder stones, an overactive bladder, or an inflammation in the prostate. Either way, it is important to get symptoms checked.

Once bladder cancer starts to spread:

  • Pain in the lower back
  • Unexplained weight loss
  • Pain in the bones
  • Extreme fatigue or exhaustion
  • The urge to urinate even when you do not have to
  • Swollen feet
  • Not feeling hungry
  • Reduced urine output

While these conditions may be a result of a condition other than bladder cancer, it is better to stay safe than be sorry.

Risk Factors and Causes of Bladder Cancer

Causes of bladder cancer

Bladder cancer is one of the most common cancers among other cancers. It affects men more than it affects women and it usually affects older adults though it can occur at any age. Bladder cancer occurs when cells in the bladder begin to grow and divide abnormally. When cells develop mutations to grow and divide uncontrollably and not die, these abnormal cells form a tumor.

Causes of bladder cancer include:

  • Smoking and other tobacco use
  • Exposure to chemicals
  • Past radiation exposure
  • Chronic irritation of the lining of the bladder
  • Parasitic infections
  • Congenital bladder abnormalities

It is not always clear what the definite causes of bladder cancer are but some patients show no obvious risk factors.

Risk factors of bladder cancer

Factors that may increase bladder cancer risk factors are:

  1. Smoking: Smoking cigarettes, cigars or pipes may cause harmful chemicals to accumulate in the urine. These toxic substances may damage the lining of the bladder which can increase the risk of cancer.
  2. Age: Bladder cancer risks increase with age. Although it is rarely found in people younger than 40 years of ae, it can occur at any age.
  3. Being white: White people have been proved to be more susceptible to bladder cancer than non-whites.
  4. Being a male: Men are more likely to develop bladder cancer than women are.
  5. Exposure to certain chemicals: Chemicals associated with bladder cancer are arsenic, those used in the manufacture of dyes, rubber, leather, textiles and paint products. The kidneys play a vital role in filtering harmful chemicals from the bloodstream and transporting them to the bladder.
  6. Former cancer treatment: Treatment with anti-cancer drug cyclophosphamide increases the risk of bladder cancer and people who have been treated with radiation aimed at the pelvis for treatment of a previous case of cancer is at an elevated risk of developing bladder cancer.
  7. Chronic bladder inflammation: Repeated urinary infection as a result of the continual use of the urinary catheter may increase the risk of developing squamous cell bladder cancer. This is also linked to a parasitic urinary infection called schistosomiasis.
  8. Family genetic history: If one has had bladder cancer once, it is very likely they get it again. If one of the first-degree relatives- a parent, sibling or child has a history of bladder cancer, one has an increased risk of developing bladder cancer. A family history of lynch syndrome (or non-polyposis colorectal cancer) can increase the risk of cancer in the urinary system, the colon, the ovaries, the uterus and other pelvic organs.

Bladder cancer diagnosis and Urine cytology

Bladder Cancer Diagnosis

Anyone who manifests signs and symptoms of bladder cancer should be evaluated. Specific pelvic regions that need evaluation are kidneys, bladder, and urethra, especially if the individual is over 40 years of age. This examination includes one or more urine tests, cystourethroscopy and an imaging test of the kidneys and ureters.

The following are important urine tests to take if cancer in the bladder is suspected:

  • Urinalysis is a test that employs a chemical indicator that changes color in the presence of certain features in the urine like white blood cells, red blood cells and glucose (sugar). The urine is also examined with a microscope.
  • Urine cytology is conducted by a pathologist who examines the sample of the urine under a microscope to check for abnormal-appearing cells that shed from the lining of the bladder.
  • Urine culture is when a sample is placed in a growth medium and monitored for signs of bacterial growth. The bacteria can be identified and the diagnosis may show an infection rather than cancer.

Imaging tests help detect any lumps or abnormalities in the kidneys, ureters, bladder or the urethra. The optimal imaging assessment (with computed tomography [CT] scan, magnetic resonance imaging [MRI], intravenous pyelogram [IVP], or kidney ultrasound) is necessary to stage the disease and formulate subsequent treatment plan.

  • CT Scan: A CT scan is an imaging test that examines the structure of the kidneys, ureters and the bladder. This helps determine if there is a blockage in the urinary tract, and determine if the cancer has spread to regions of the body outside the bladder. CT scans are conducted with the help of a contrast dye.
  • Pyelogram: This is a contrast dye injected into the bladder either by a vein or by a direct catheter. The dye outlines the bladder and associated organs, making any tumors visible on the X-rays.
  • Ultrasound and sonography: There determine the size and the spread of the tumor. They particularly use sound waves to image abnormalities.
  • MRI: A magnetic resonance imaging of the kidneys, ureters, and bladder is employed to evaluate the urinary tract. This imaging may provide useful information in staging of the bladder cancer.
  • IVP: Here a radiopaque dye (one that is visible on X-ray) is injected into the vein. The dye collects in and is excreted by the kidneys. As the dye passes through the urinary drainage system any abnormal lumps may be detected on X-ray images. It might be useful to note that there is a small risk of having an allergic reaction to the dye. People who are allergic to contrast dye, iodine or shellfish should let the radiologist know.
  • Cystoscopy: A cystoscopy is a procedure that is done to directly visualise the lining of the urethra and bladder. It can be conducted by a urologist/oncologist in an operating room. Also known as the cystourethroscopy, an anesthetic gel is applied to the urethra to avoid discomfort and a small tube with a camera (cystoscope) is then inserted into the bladder through the urethra.

Biopsy

Apart from these imaging tests, a biopsy exclusively for the examining of abnormal tissue can be taken. This may be examined in a laboratory or an operating room. Biopsy is usually done as an office procedure by cystoscopy.

Transurethral resection of bladder tumor(TURBT)

Upon diagnosis of bladder cancer, imaging tests are performed. This is followed by resection of bladder mass by cystoscopy under anesthesia to confirm the extent of tumor, a procedure called TURBT. Further the tumor can be classified as invading the muscle or not which has a bearing on further treatment planning.

Different Stages of Bladder Cancer

Bladder cancer staging

The treatment and prognosis of bladder cancer depend upon its stage, its grade, and the risk that the cancer will recur. After diagnosis of bladder cancer, the doctor sets out to determine if it has spread and how far it has spread. This process is called staging of cancer. Staging is important to determine what treatment plan needs to be drawn out and if it will be successful.
Bladder cancer staging is based upon how far the cancer has penetrated into the tissues of the bladder, whether the cancer involves lymph nodes near the bladder, and if the cancer has reached nearby organs and distant sites. Staging is dependent on the physical examinations, imaging tests, and biopsies that have been listed out at length above.

Understanding the stages of bladder cancer

The American Joint Committee on Cancer (AJJCC) has developed a system of staging called the TNM staging which is based on three important elements of the cancer.

T determines the extent to which the (primary) tumor has grown through the bladder wall and whether it has grown into nearby tissues.

N indicates if the cancer has spread to lymph nodes near the bladder. Lymph nodes are bean-sized collections of immune system cells, to which cancers often spread first.

M indicates if the cancer has spread (metastasized) to other organs in distant sites like the lungs or liver, or lymph nodes that are not near the bladder.

Number stages also aid in determining the spread of the cancer.

Stage 0

The cancer is in the origin of its site in the inner layer of the bladder lining (stage 0a) or R there are very early, high grade cancer cells only in the inner layer of the bladder lining (stage 0is).

Stage 1

The cancer has started to invade the connective tissue beneath the bladder lining.

Stage 2

The cancer has metastasized through the connective tissue layer into the muscle of the bladder wall.

Stage 3

The cancer has spread beyond the muscle into the fat layer and may have spread to the prostate, womb or vagina or lymphnodes.

Stage 4

The cancer has spread to the wall of the tummy (abdomen) or between the hips (pelvis), to other distant parts of the body like the bones, lungs or liver.

Chemotherapy Treatment for Bladder Cancer

Chemotherapy is the use of drugs to treat cancer by killing the tumor cells. It normally follows protocols of specific cycles or regimens. Moreover, after each period of treatment there is a period of rest that allows the body time to recover. During the treatment of bladder cancer, chemotherapy administration may happen in the following ways:

  • Intravesical chemotherapy

Here the chemo drug is put right into the bladder. This type of chemo is used for bladder cancer that is only in the lining of the bladder.

  • Systemic chemotherapy

Here, the administration of chemotherapy drugs happens in pills or injected into the vein (IV) or muscle (IM). In systemic chemotherapy, the drugs enter the bloodstream and are course throughout the body. This is an effective method as the drugs can access cancer cells anywhere in the body. Generally, there are two modes of administration:

a. Neoadjuvant therapy: Precedes surgery to shrink the tumor so that it is easier to remove and help lower the chances of cancer relapse.
b. Adjuvant therapy: Generally, follows surgery and sometimes follows radiation therapy. The goal of adjuvant therapy is to kill any cancer that may remain after other treatments. Besides, this lowers that chance of cancer recurrence.

Systemic chemotherapy helps radiation work better. Moreover, it is the primary treatment treatment of for metastatic bladder cancers.

Chemotherapy drugs in the treatment of bladder cancer

Chemotherapy can be solitary or in combination with other treatment modalities depending on the general health of the patient.

Chemo in combination with radiation commonly includes drugs such as:

  • Cisplatin
  • Cisplatin plus fluorouracil (5-FU)
  • Mitomycin with 5-FU

Furthermore, most common combinations of chemo without radiation include:

  • Gemcitabine and cisplatin
  • Dose-dense methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin (DDMVAC)
  • Cisplatin, methotrexate, and vinblastine (CMV)
  • Gemcitabine and paclitaxel

Furthermore, read about the side-effects of chemotherapy here.

Radiation Therapy Treatment For Bladder Cancer

Radiation therapy or radiotherapy uses high-energy rays to kill cancer cells by preventing their growth and rapid division. It consists of local treatment that delivers waves within the radiation field either externally or internally. External radiation delivers high-energy rays directly to the cancer from a machine outside the body. Internal radiation, or brachytherapy, involves the implantation of a small amount of radioactive material in or near the cancer.

Before treatment of bladder cancer with radiotherapy, simulation, a planning process helps make careful measurements to find exact angles for administration and the right dosage. It may include imaging tests like CT or MRI scans.

During simulation, patients lay on a table somewhat similar to the one in a CT scan. Adjustments of height and rotation around a central axis is possible. The ‘simulator’ machine is a machine whose dimensions and movements closely match that of an actual linear accelerator. The simulator lets the radiation oncologist and technologists treat the tumor by projecting an image of it.

The simulator room is periodically darkened while the treatment fields are being set and temporary marks may be made on the patient’s skin with the help of markers. The radiation oncologist is aided by one or more radiation technologists and often a dosimetrist, who performs calculations necessary in the treatment planning. The simulation may last anywhere from 15 minutes to an hour or more, depending on the complexity of the plan.

Furthermore, read about the side effects of radiotherapy in the treatment of bladder cancer.

Palliative Radiation

Palliative therapy helps reduce the symptoms of cancer and ultimately improve the patient’s quality of life. For some patients with advanced bladder cancer, radiation therapy may help shrink cancer lumps and relieve cancer symptoms.

Administration of radiation therapy today for bladder cancer happens through linear accelerators. These accelerators produce high energy external radiation beams that penetrate the tissues and deliver the radiation dose into deeper areas. These modern machines and other state-of-the-art techniques significantly reduce side effects. Moreover, they help improve the ability to deliver a curative radiation dose to cancer-containing areas and minimizing the radiation dose to normal tissue.

X-rays representing the treatment fields  follow the positioning of the treatment fields. In most centers, the oncologist marks the patient multiple places which punctate the radiation field. These marks look like pin pricks and they are subject to renewal each day.

The administration of radiation treatment happens in a room separate from the simulation room. The treatment plans and treatment fields that result from the simulation session are transferred over to the treatment room. The latter contains a linear accelerator that focusses on a patient table similar to the one in the simulation room. However, treatment starts only when the field and calculations are accurate.

Doctors may prescribe radiation therapy in combination with chemotherapy for treatment of patients with stage II-III disease or recurrent cancer. However, radical cystectomy remains the primary modality for the treatment of stages II bladder cancer and treatment of stage III bladder cancer

Other Treatment Options for Bladder Cancer

Biological therapy or Immunotherapy

Oncologists treat low grade and early stage cancers by inducing the immune system to fight the cancer cells and kill them. This is called biological therapy or immunotherapy. The most common form of biological therapy is Bacillus Calmette-Guerin therapy (BCG). Moreover, this bacterium causes tuberculosis (TB). In BCG therapy, a catheter helps kill this this bacterium by insertion into the bladder.

What is intravesical BCG

The BCG bacteria activate the immune system cells, which can fight any bladder cancer cells that are present. Moreover, this can be put into the bladder as a liquid (intravesical BCG). This treatment is for once a week for 6 weeks. It often begins shortly carrying out a TUR. A TUR (or transurethral resection) is a surgical procedure for the diagnosis of bladder cancer and removal of tumor lumps from the bladder.

Another immunotherapy option is interferons. IFNs are a group of signalling proteins that fight infection. A virus-infected cell releases interferons causes surrounding cells improve to their antiviral defences. Furthermore, synthetic versions of interferons help fight bladder cancer, sometimes in combination with BCG.

Possible side effects of immunotherapy

Common side effects of these drugs include:

  • Tiredness
  • Nausea and vomiting
  • Loss of appetite
  • Fever
  • Urinary tract infections (UTIs)
  • Rash and skin allergies
  • Diarrhea
  • Constipation

Besides, more serious side effects can occur. These drugs work by basically taking the brakes off the body’s immune system. Sometimes the immune system starts attacking other parts of the body. Consequently, this causes life-threatening problems in the lungs, intestines, liver, hormone-making glands, or other organs.

It is very important to report any new side effects to your health care team right away. However, if serious side effects do occur, oncologists stop treatment  and administer high doses of steroids to suppress your immune system.

Bladder Cancer Surgery

Surgery is an important treatment modality for most bladder cancers. The type of surgery depends on the extent or the stage of the cancer, and other factors like the age of the patient, preference and long-term side-effects that surgery can cause.

Transurethral resection of bladder tumor (TURBT)

A transurethral resection of bladder tumor (TURBT) or a transurethral resection (TUR) helps detect bladder cancer. It also provides information on whether the cancer has metastasized into the muscle layer of the bladder wall. TURBT is a common treatment for early-stage non-muscle invasive bladder cancers. In some cases, a second, more extensive TURBT makes sure there is no relapse.

TURBT involves insertion of a tube in through the patient’s urethra so there is cutting open the abdomen. General anesthesia by drugs or by local anesthesia where the lower portion of the body goes numb. Then inserting of thin, rigid cystoscope (a resectoscope) into the patient’s bladder helps access tumor cells. The resectoscope has a wire loop at one end. This is used to remove any abnormal tissues or tumors. This tissue goes for testing in the lab through a biopsy.

After removal of the tumor via surgery, fulguration ensures that no tumor cells are remain. This method basically involves high-laser treatment of of any remaining cells through the resectoscope.

Cystectomy

When bladder cancer is invasive, oncologists advise a cystectomy. In most cases, chemotherapy goes before cystectomy. General anesthesia preceded for both types of cystectomy, partial or complete.

Partial cystectomy

If cancer is still small but is invasive (into the muscle layer of the bladder wall), surgery removes it along with part of the bladder wall. The punctures in the bladder wall are then stitched up. Then, there is a removal of nearby lymph nodes for testing of cancer metastasis. An advantage that partial cystectomy has over other surgeries are that bladder conservation is possible and there is no requirement of reconstructive surgery. Disadvantages of this surgery are that the bladder may be incapable functioning at normalcy or that the cancer may relapse.

Radical cystectomy

If the cancer is not large or is prevalent in a greater part of the bladder, a radical cystectomy is the first option. This operation involves removing the entire bladder and nearby lymph nodes. In men, there is removal of the prostate and seminal vesicles. In women, the ovaries, fallopian tubes, the uterus , cervix, and a small part of the vagina are removed.

Most of the time, a surgeon carries out a cystectomy with an incision in the abdomen. A week at the hospital and a few more weeks of rest at home should suffice before the patient gets back to normal activities.

In a laparoscopic, or ‘keyhole’ surgery, the surgeon may operate through many smaller incisions using special long, thin instruments, one of which has a tiny video camera on one end to see inside the patient’s body. The surgeon may either hold the instruments directly or may sit at a control panel in the operating room and use robotic arms to do the surgery (a robotic cystectomy). This type of surgery may result in less pain and quicker recovery because of the smaller cuts. Research is still underway for improvisations and to make it more efficient.

It is important that a surgeon with experience in treating bladder cancer conduct the cystectomy. If the surgery does not go well, the cancer is likely to come back.

Reconstructive surgery after radical cystectomy

If removal of the bladder is a must, an alternative is made to store urine which is voided intermittently. The following are a few options:

1. Incontinent diversion

One of the options is to remove and clean a short piece of the intestine and then connect it to the ureters the tubes that carry urine out of the kidneys. The creation of an ileal conduit allows for urine to pass from the kidneys to the outside of the body. The urine then flows directly from the kidneys through the ureters into the ileal conduit. One end of the conduit connects the skin on the front of the abdomen by an opening called a stoma (a urostomy).

After this procedure, a small bag sticks to the skin of the patient’s belly around the stoma to collect the urine. Urine slowly drains out non-stop which means the uro-bag must be on all the time. It empties whenever it is full. This procedure is known known as incontinent diversion, because the patient cannot control the flow of urine out of the body.

2. Continent diversion

Another option for urine to drain is a continent diversion. Here, a pouch made from a piece of intestine is attached to the ureters. One end of the pouch is connects to an opening or the stoma in your skin on the front of your belly. Surgery creates a one-way valve at this opening. This allows the storage of urine in the pouch. The patient then empties it several times a day by inserting a catheter into the stoma through the valve. This method is preferable because of the absence of the uro-bag.

3. Neobladder

This method routes the urine back into the urethra where there is no hindrance to passing urine regularly. This surgery creates a new bladder or a neobladder from a piece of intestine. The ureters are sewn to the neobladder letting the patient urinate normally on a schedule. There is no urge to urinate which demand for a schedule. Over time, most patients regain the ability to urinate normally during the day, but incontinence may persist at night.

If cancer has spread, surgery cannot remove it. A diversion may be made without taking out the bladder. In this case, the purpose of the surgery is to prevent or relieve blockage of urine flow, rather than try to cure the cancer.

Drugs Used In The Treatment Of Bladder Cancer

Drugs Approved for Bladder Cancer

  • Atezolizumab
  • Avelumab
  • Bavencio (Avelumab)
  • Cisplatin
  • Doxorubicin Hydrochloride
  • Durvalumab
  • Imfinzi (Durvalumab)
  • Keytruda (Pembrolizumab)
  • Nivolumab
  • Opdivo (Nivolumab)
  • Pembrolizumab
  • Tecentriq (Atezolizumab)
  • Thiotepa
  • Valrubicin
  • Valstar (Valrubicin)

Furthermore, drugs used in combination for treatment of bladder cancer are:

  • GEMCITABINE-CISPLATIN
  • MVAC

Prevention Of Bladder Cancer

How to prevent Bladder Cancer?

There is no guaranteed way to prevent bladder cancer as is the case for any cancer. But there are guidelines to follow through considering the risk factors of bladder cancer:

  • Don’t use tobacco: Smoking or chewing tobacco increases exposure to carcinogenic substances. Deaddiction treatment, support groups, medications and other methods can help one quit smoking. Read more on 10 Tips On How to Quit Smoking 
  • Take caution around chemicals: It is important to follow instructions when handling chemical substances.
  • Choose a variety of fruits and vegetables: A diet with a variety of fruits and vegetables may help reduce the risk of bladder cancer.
Book an expert blood cancer specialist from Onco
Newsletter

Enter your email address below to subscribe to our newsletter