Bladder Cancer

The bladder is a hollow organ that collects urine from the kidneys through the ureters for storage and eventual removal from the body through the urethra. Bladder cancer is an uncontrolled abnormal growth and multiplication of cells in the urinary bladder, which have broken free from the normal mechanisms that keep uncontrolled cell growth in check. Invasive bladder cancer (like cancers of other organs) has the ability to spread (metastasize) to other body parts, including the lungs, bones, and liver.  Bladder cancer is a common cancer; men have a higher risk of getting bladder cancer than women. Cigarette smoking is the most significant risk factor for bladder cancer, with smokers three to four times more likely to get the disease than nonsmokers. There are two subdivisions of bladder cancer: noninvasive, or superficial, and invasive, with the former having much better treatment outcomes than the latter.

What are the types of Bladder Cancer?

  • Urothelial carcinoma (previously known as “transitional cell carcinoma”) is the most common type and comprises 90%-95% of all bladder cancers. This type of cancer has two subtypes: papillary carcinoma (growing finger-like projections into the bladder lumen) and flat carcinomas that do not produce fingerlike projections. Urothelial carcinoma (transitional cell carcinoma) is strongly associated with cigarette smoking.
  • Adenocarcinoma of the bladder comprises about 1%-2% of all bladder cancers and is associated with prolonged inflammation and irritation. Most adenocarcinomas of the bladder are invasive.
  • Squamous cell carcinoma comprises 1%-2% of bladder cancers and is also associated with prolonged infection, inflammation, and irritation such as that associated with longstanding stones in the bladder. In certain parts of the Middle East and Africa (for example, Egypt), this is the predominant form of bladder cancer and is associated with chronic infection caused by Schistosoma worm (a blood fluke, that causes schistosomiasis, also termed bilharzia or snail fever).
  • Other rare forms of cancer found in the bladder include small cell cancer (arising in neuroendocrine cells), pheochromocytoma (rare), and sarcoma (in muscle tissue).

Signs & Symptoms of bladder cancer:

The most common symptom of bladder cancer is bleeding in the urine (hematuria). Most often the bleeding is “gross” (visible to the naked eye), episodic (occurs in episodes), and is not associated with pain (painless hematuria). However, sometimes the bleeding may only be visible under a microscope (microscopic hematuria) or may be associated with pain due to the blockage of urine by formation of blood clots. There may be no symptoms or bleeding for prolonged periods. Some types of bladder cancer may cause irritative symptoms of the bladder with little or no bleeding. The patients may have the desire to urinate small amounts in short intervals (increased urinary frequency), an inability to hold the urine for any length of time after the initial desire to void (urgency), or a burning sensation while passing urine (dysuria).

Diagnosis of Bladder Cancer:

Bladder cancer is most frequently diagnosed by investigating the cause of bleeding in the urine that a patient has noticed. The following are investigations or tests that come in handy in such circumstances:

  • Urinalysis: A simple urine test that can confirm that there is bleeding in the urine and can provide an idea about whether an infection is present or not. It is usually one of the first tests that a physician requests. It does not confirm that a person has bladder cancer but can help the physician in short-listing the potential causes of bleeding.
  • Urine cytology: A health care professional performs the test on a urine sample that is centrifuged. Then a pathologist examines the sediment under a microscope. The idea is to detect malformed cancerous cells that may pass into the urine from a cancer. A positive test is quite specific for cancer (for example, it provides a high degree of certainty that cancer is present in the urinary system). However, many early bladder cancers may be missed by this test so a negative or inconclusive test does not effectively rule out the presence of bladder cancer.
  • Ultrasound: An ultrasound examination of the bladder can detect bladder tumors. It can also detect the presence of swelling in the kidneys in case the bladder tumor is located at a spot where it can potentially block the flow of urine from the kidneys to the bladder. It can also detect other causes of bleeding, such as stones in the urinary system or prostate enlargement, which may be the cause of the symptoms or may coexist with a bladder tumor. An X-ray examination may rule out other causes of symptoms.
  • CT scan/MRI: A CT scan or MRI provides greater visual detail than an ultrasound exam and may detect smaller tumors in the kidneys or bladder than can be detected by an ultrasound. It can also detect other causes of bleeding more effectively than ultrasound, especially when intravenous contrast is used.
  • Cystoscopy and biopsy: This is probably the single most important investigation for bladder cancer. Since there is always a chance to miss bladder tumors on imaging investigations (ultrasound/CT/MRI) and urine cytology, it is recommended that all patients with bleeding in the urine, without an obvious cause, should have a cystoscopy performed by a urologist as a part of the initial evaluation. This entails the use of a thin tube-like optical instrument connected to a camera and a light source (cystoscope). A health care provider passes it through the urethra into the bladder and the inner surface of the bladder is visualized on a video monitor. Small or flat tumors that may not be visible on other investigations are visible by this method, and a piece of this tissue can be taken as a biopsy for examination under the microscope. This method effectively diagnoses the presence and type of bladder cancer. In addition, health care professionals may perform fluorescence cystoscopy at the same time; fluorescent dyes are placed in the bladder and are taken up by cancer cells. These cancer cells are visible (fluoresce) when a blue light is shined on them through the cystoscope and thus become visible, thereby making identification of cancer cells easier with this technique.
  • Newer biomarkers like NMP 22 and fluorescent in-situ hybridization (FISH) are currently in use to detect bladder cancer cells by a simple urine test. UroVysion, BTA, and the ImmunoCyt test are newer diagnostic tests. However, they have not yet achieved the level of accuracy to replace cystoscopy and cytology in the diagnosis and follow-up of bladder cancer.

Staging & Grading:

The proper staging of bladder cancer is an essential step that has significant bearings on the management of this condition. A pathologist examines the tumor specimen under a microscope to determine the grading of the bladder cancer. It is a measure of the extent by which the tumor cells differ in their appearance from normal bladder cells. The greater the distortion of appearance, the higher the grade assigned. High-grade cancers are more aggressive than low-grade ones and have a greater propensity to invade into the bladder wall and spread to other parts of the body. The grades are-

  • Grade 1 cancers (or low grade or well differentiated cancers) have cells that look very much like normal cells. They tend to grow slowly and are not likely to spread.
  • Grade 2 cancers have cells that look more abnormal. They are called medium grade or moderately differentiated and may grow or spread more quickly than low grade.
  • Grade 3 cancers have cells that look very abnormal. They are called high grade or poorly differentiated and are more quickly growing and more likely to spread.
  • Grade 4 cancers are so abnormal that they have no distinguishing features to say that they even started as bladder cells. They are undifferentiated.

Treatment:

The initial surgical procedure that a patient undergoes after the diagnosis of bladder cancer is established is usually a transurethral resection of bladder tumor or “TURBT.” This does not involve an external cut on the body. For Superficial Bladder Cancer, after an initial TURBT, patient may be put on follow up with repeated cystoscopic examinations. For high grade superficial cancers, Intravesicular instillation of BCG vaccine and for recurrent tumors intravesicular instillation of Mitomycin-C or Adriamycin are used.

For Invasive bladder cancer, the preferred treatment is surgical approach. But an organ preservative Radical Chemo Radiotherapy is also used.