Bladder Cancer

Bladder cancer, although not a very common cancer in Malaysia, can be a very aggressive tumor in the later stages of the disease and may lead to psychosocial distress due to the need for surgical intervention.

It occurs more frequently in males than in females, and is, in fact, the sixth most common cancer among males in Malaysia.

Age-wise, this cancer tends to mostly affect those aged 65 years and above.

The good news is that about seven out of every 10 bladder cancers are diagnosed at a very early stage, when it is treatable.

The bad news is that there is as high as a 70% chance of recurrence, therefore survivors need to be followed-up for many years to see if the cancer returns.

For muscle-invasive bladder cancer, a major surgery with bladder removal and urinary diversion is needed for treatment, which often causes psychosocial distress to the patient.

The risk factors for bladder cancer are smoking and exposure to chemicals used in dye factories, latex (especially for rubber tappers), leather, textiles, printing, plastics, paints and other chemical industries.

In clinical practice, the most common risk factor is smoking.

Repeated inflammation of the bladder from untreated bladder stones and radiotherapy to the pelvis can also result in this cancer.

Unfortunately, some people with bladder cancer have no obvious risk factors.

Bladder cancer signs and symptoms can include:

  • Blood in urine (haematuria)
  • Painful urination
  • Pelvic pain
  • Back pain
  • Having to urinate more than usual
  • Feeling the urge to urinate even if the bladder is not full
  • Lower back pain on one side
  • Weak urine stream
  • Fatigue and weakness
  • Loss of appetite and weight

The most common complaint doctors usually hear is painless blood in the urine. The blood may not be visualized in your urine without a microscope.

If you have this symptom, you should ideally see the urologist within two weeks of your symptoms occurring.

Assessment

The urologist will assess your kidneys, ureter and bladder through an intravenous urogram (IVU) or a CT (computed tomography) scan, followed by an endoscopic examination of your bladder through your urinary passage (cystoscopy).

The cystoscopy is relatively painless, although there may be some discomfort, and can easily be done with local anesthesia.

Even if the blood in your urine goes away, you should still meet the urologist for a proper assessment as the blood passage may be intermittent, and the next episode of blood in the urine may occur very much later when the bladder cancer has already progressed to an advanced stage.

Blood in the urine does not always indicate bladder cancer though. It may occur due to stones, infection, benign vascular malformation and various other causes.

However, bladder cancer should always be ruled out first before assuming this symptom is due to other causes.

Cystoscopy – endoscopy of the urinary bladder. Pic from National Cancer Institute NCI

The cystoscopy procedure is relatively painless.

A cystoscope (a thin, tube-like instrument with a light and a lens for viewing) is inserted through the urethra into the bladder. Fluid is used to fill the bladder. The doctor looks at an image of the inner wall of the bladder on a computer monitor.

 

The typical appearance of a bladder cancer on cystoscopy:

Endoscopic images of bladder cancer on cystoscopy

Staging

Image of bladder cancer and its various stages

Ta and T1 diseases are known as superficial disease and needs follow-up after TURBT surgical resection of the tumor.

T2, T3 and T4 diseases are known as muscle-invasive disease which requires bladder removal and urinary diversion.

Staging to treatment

Bladder cancer may be broadly staged as superficial disease, muscle invasive disease and advanced disease, depending on how many layers of the bladder wall have been invaded.

Proper staging of the bladder cancer is required before deciding on treatment. It is essential to determine firstly if the bladder cancer is superficial or muscle-invasive. And then to determine if there is spread outside the bladder.

For this, CT scan imaging should be done for for muscle-invasive disease, as well as for assessment of the upper urinary tracts for cancer.

Bladder cancer staged from a CT scan

Superficial bladder cancer

Superficial disease is highly treatable without needing to remove the bladder.

Known as TURBT (transurethral resection of bladder tumour), this treatment involves inserting a cystoscope through your urethra into your bladder to remove the tumour.

Transurethral resection of bladder tumor (TURBT) – is a very important technique to determine the type, stage, and grade of bladder cancer. This procedure is performed to see inside the bladder, take a tumor sample, and resect the tumor from the bladder wall. This is then sent for histopathological analysis.

On resection with TURBT, it will confirm if the cancer is superficial or muscle-invasive.

There are times when a second stage TURBT needs to be done if there is a high grade cancer which initially appears to be superficial, for which then a second TURBT may confirm muscle-invasive disease.

For superficial disease, chemotherapy or other medications might then be passed into the bladder for local treatment, known as intravescial chemotherapy. Unlike intravenous (IV) chemotherapy, the chemotherapy instilled into the bladder does not cause nausea, loss of hair, loss of appetite or loss of weight, and is very well tolerated.

Superficial bladder cancer, in most instances, requires life-long follow-up and surveillance in case the cancer recurs.

Resection of bladder tumor with a TURBT. This is done under anesthesia.

Muscle Invasive Bladder Cancer

Muscle invasive disease, on the other hand, has a high risk of progressing to advanced disease. Removing the bladder and its surrounding lymph nodes at this stage is a vital part of treatment to prevent spread of the disease and to achieve cure. The removal of the bladder in deep (muscle invasive) bladder cancer is the best way to achieve cure in muscle invasive bladder cancer.

Bladder removal in deep (muscle invasive) bladder cancer

The removal of the bladder in deep (muscle invasive) bladder cancer is the best way to achieve cure in muscle invasive bladder cancer.

When the bladder is removed with its surrounding lymph nodes, the bladder needs to be substituted with a urinary conduit or a reservoir. This can be achieved by utilizing the small or the large intestine, re-model it into a conduit or a reservoir, and to establish continuity of the urinary tract system.

This surgery is among the most complex urological operations, with considerable morbidity and prolonged hospital stay. Complications after bladder removal have been reduced in the current era, mostly due to improved operative techniques, better anesthetic management and evolution of perioperative medical care.

After the bladder is removed, it needs to be substituted with a urinary conduit or a reservoir. This can be achieved by utilizing a part of the small or large intestines and remodeling it into a conduit or a reservoir that is connected to the urinary tract system.

Those who prefer an intestinal conduit will have a stoma placed in the abdominal wall where their urine can exit into a urostomy bag.

Those who prefer a neobladder will have the option of not having any stoma as the neobladder acts as a reservoir connected to the ureters and urethra, allowing for voluntary urination.

Urinary diversion after bladder removal: (Illustrations from the 2016 ACS NSQIP Annual Conference)

Other modalities of treatment

Aside from surgery, there are various other options for treatment, including radiotherapy, chemo-radiotherapy and partial removal of the bladder. However, these are reserved for a small group of patients who have multiple medical illnesses and are not fit for surgery. The cure rate for these patients is lower than those who undergo surgical treatment.

Surgical treatment of removal of the bladder as a whole and removal of the lymph nodes (Radical cystectomy with pelvic lymph node dissection), and anterior exanteration in females (removal of uterus and part of the vagina) is the standard treatment of muscle-invasive bladder cancers so as to achieve cure.

The intestinal conduit formation and urostomy bag

When the bladder is removed with its surrounding lymph nodes, the bladder needs to be substituted with a urinary conduit or a reservoir. This can be achieved by utilizing the small or the large intestine, re-model it into a conduit or a reservoir, and to establish continuity of the urinary tract system.

After the bladder is removed, it needs to be substituted with a urinary conduit or a reservoir. This can be achieved by utilizing a part of the small or large intestines and remodeling it into a conduit or a reservoir that is connected to the urinary tract system.

Those who prefer an intestinal conduit will have a stoma placed in the abdominal wall where their urine can exit into a urostomy bag (usually an ileal conduit).

Those who prefer a neobladder will have the option of not having any stoma as the neobladder acts as a reservoir connected to the ureters and urethra, allowing for voluntary urination.

This surgery is among the most complex urological operations, with considerable morbidity and prolonged hospital stay.

However complications after bladder removal have been reduced in the current era, mostly due to improved operative techniques, better anesthetic management and evolution of perioperative medical care.

Intestinal conduit and anastomosis of intestine

Illustration of the intestinal conduit

Intestinal conduit

The neobladder and an intestinal pouch after bladder removal

Advanced bladder cancers is said to occur when the cancer has spread outside the bladder to other organs. This may be treated with chemotherapy, but in the past few years a number of targeted agents, in particular the checkpoint inhibitors, have been approved for specific indications in advanced disease. Advanced disease occurs when the cancer has spread to the liver, lungs, distant lymph nodes and/or bones, among other organs.

In these cases, cure may not be achieved, but chemotherapy and the newer targeted agents, including immune checkpoint inhibitors, can help prolong life.

It should also be noted that the bladder’s inner lining, known as the urothelium, is a continuous lining from the kidneys above to the ureter, bladder and urethra below.

Thus, a person with bladder cancer may also harbor cancer deposits in the kidney, ureter and the urethra simultaneously, or may have a recurrence in these areas during follow-up later.

The following is the summary of the interventions that are being generally considered to treat bladder cancer patients:

TURBT – this is the endoscopic resection of your bladder done to confirm the diagnosis of bladder cancer, as well as the definitive treatment for superficial bladder cancers.

ImmunotherapyBacillus Calmette-Guerin (BCG), a bacteria of low pathogenic potential, is used for treating high grade and aggressive superficial bladder cancer. A catheter is used to administer BCG directly into the bladder, which in turn activates the body’s immune system. Activated immune cells then attack and destroy cancer cells. Symptoms associated with this immune therapy include, but are not limited to fever, cold, and fatigue.

Intravesical Chemotherapy – This is used in low grade and intermediate grade superficial bladder cancers. Chemotherapy is instilled into the bladder as an adjuvant therapy after TURBT, and then followed by weekly therapy for 6 weeks. There are hardly any side effects by instilling this into the bladder as compared to the regular IV (intravenous) chemotherapy.

Radical cystectomy this surgical procedure includes removal of the entire bladder, adjacent lymph nodes, and a part of the urethra done for muscle-invasive bladder cancers. During surgery, the prostate can also be removed in men, and in women, the uterus, fallopian tube, ovaries, and vaginal wall can be removed.  

Pelvic lymph node dissectionthis procedure is used to check for lymph node spread.

Radiation therapyit is a post-operative treatment strategy that is performed together with chemotherapy. It uses high-energy beams of radiation to destroy cancer cells. Common side-effects related to this therapy are nausea, vomiting and diarrhea.

Neoadjuvant chemotherapyit is usually performed together with cystectomy. In chemotherapy, an anti-cancer drug or a combination of drugs is administered intravenously to kill cancer cells and reduce the size of the tumor, prior to surgery. This therapy comes with many side-effects, including reduced appetite, nausea, vomiting, hair loss, reduced blood cell count, infection, weakness and fatigue, and numbness in the hands and feet, among others. However, the best way to achieve cure is to have neo-adjuvant chemotherapy before bladder removal. It is best you discuss these issues with your urologist.

 

Summary of treatment modalities for bladder cancer

Superficial bladder cancer

Transurethral resection of bladder tumor (TURBT) is a very important technique to determine the type, stage, and grade of bladder cancer. This procedure is performed to see inside the bladder, take tumor sample, and resect the tumor from the bladder wall. This is followed by intravesical chemotherapy or BCG

Muscle-invasive bladder cancer

The golden standard for treating muscle-invasive bladder cancer is radical cystectomy with extended pelvic lymph node dissection, with or without chemotherapy.

Advanced bladder cancers

May be treated with chemotherapy, a number of targeted agents, in particular the checkpoint inhibitors.

Prevention

Primary prevention

There are a few ways to reduce the risk of bladder cancer:

  • Stop smoking

Smoking is the biggest and most common risk factor for bladder cancer.

  • Beware of chemicals

If you work with chemicals, follow all safety instructions to avoid exposure.

And follow the necessary protocols in occupational screening for cancers.

Secondary prevention

If you have blood in the urine, either visible or identified during urine microscopic examination, see your urologist within two weeks of discovering the symptom.

Even if it goes away, you should still meet the urologist for a proper assessment.

Blood in the urine is the most common symptom of bladder cancer and should not be ignored.

You can achieve a reasonably high cure rate if bladder cancers are diagnosed early.

There are also a number of common myths, misconceptions and inaccuracies surrounding the issue of blood in the urine and bladder cancers:

Antibiotics will NOT help

The presence of blood in the urine does not imply that a course of antibiotics should be tried with the hope that the blood in the urine will disappear.

The blood may disappear, but the cancer will not.

Antibiotics are only indicated for urinary infection, based on the symptoms and suspicion of an infection.

Painless blood in the urine requires immediate referral to the urologist, and not a trial of a course of antibiotics.

Water will NOT clear it

Drinking more water with the hope of clearing the blood in the urine will not clear the cancer away.

Traditional medications are NOT a cure

Traditional and herbal medications will not cure or reduce bladder cancers.

Bladder cancer is NOT contagious

Bladder cancer is not contagious and will not spread to other family members or people close to the patient.

Local chemotherapy side effects are NOT horrible

The local instillation of chemotherapy into the bladder for superficial bladder cancers will not give the bad side effects of regular IV (intravenous) chemotherapy.

When to see the urologist

  • Blood in urine (haematuria)
  • Painful urination
  • Pelvic pain
  • Back pain
  • Having to urinate more than usual
  • Feeling the urge to urinate even if the bladder is not full
  • Lower back pain on one side
  • Weak urine stream
  • Fatigue and weakness
  • Loss of appetite and weight

If you have these symptom, especially hematuria (blood in the urine), you should ideally see the urologist within two weeks of your symptoms occurring.

Hematuria (blood in the urine) is a very important symptom. As per current guidelines, if you have blood in the urine, you will have to see a urologist preferably within 2 weeks of onset of the symptoms.

Anyone with hematuria need to be properly evaluated and important causes of hematuria ruled out early.

The evaluation consists of upper tract imaging (CT Urography with contrast) AND cystoscopy (endoscopy of your bladder).

Practice-pattern assessments have demonstrated significant deficiencies in the evaluation of patients presenting with hematuria.

One study found that less than 50% of patients with hematuria diagnosed in a primary care setting were subsequently referred for urologic evaluation.

The underuse of cystoscopy, and the tendency to rely solely on imaging for evaluation, is particularly concerning since the vast majority of cancers diagnosed among persons with hematuria are bladder cancers, optimally detected with cystoscopy.