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Bladder - Bladder Cancer
By Ihor S. Sawczuk, M.D.
THE BLADDER:
The urinary bladder is an important part of the urinary tract. It is a muscular sac that collects and stores urine. Kidneys filter the blood forming urine, which is made up of water and waste products. Urine flows from the kidneys to the bladder (through two tubes known as right and left ureters) where it is stored until it can be released from the body. The inside of the bladder is lined with microscopic transitional cells, which have the ability to expand and deflate. Below this superficial layer of cells is the muscle layer.
THE CANCER:
Cancer is a disease caused by loss of normal control of cell growth, results in unregulated growth (tumor), lack of differentiation (Maturation of the growing cells to finally look like the original tissue), local tissue invasion (spread of the disease to the surrounding tissues), and metastasis (spread of the disease through blood stream or lymph channels to distant parts of the body). Cancer can develop in any tissue of any organ at any age. Most cancers are potentially curable if detected and treated at early stage.
THE INCIDENCE:
Cancer of the bladder is the second most common cancer of the urinary system; also it is the fourth most common cancer among men and the ninth most common cancer among women. About 38,500 men and 13,000 women will develop the disease each year. Cancer of the bladder may occur at any age, but it usually strikes those over 50 years old.
If detected and treated early, bladder cancer is almost always cured (the 5-year survival rate of early bladder cancer is 90%). Unfortunately, less than one in ten patients with metastatic bladder cancer survive five or more years. Each year about 6,000 men and 3,000 women will die of the disease. During the past 30 years, the death rate for bladder cancer has declined slightly for men, more so for women. This success is attributed to earlier detection and better treatment options.
THE CAUSES:
Bladder cancer is known to occur more frequently in workers in certain industries where there is probable carcinogen exposure; these industries include textiles, hairdressing, roofing, and chemical and medical/laboratory workers. Cigarette smokers also develop bladder cancer nearly three times as often as non-smokers. The number of cigarettes smoked each day, the tar content, and the duration of the smoking habit all increase the likelihood of developing bladder cancer.
THE TYPES:
Most bladder cancers are due to abnormal growth of the lining and are called transitional cell cancers (TCC), superficial or invasive:
Superficial tumors: They are present in 80% of cases of TCC at initial presentation. Superficial TCC includes carcinoma in situ (TIS), which is flat TCC that may occur diffusely or as focal lesions and in the presence or absence of associated superficial or invasive tumors. Papillary (finger like) tumors confined to the lining of the bladder (Ta), and lesions with invasion into the lamina propria (T1), which is the connective tissue layer deep to the bladder lining cells. The superficial tumors are less threatening to one’s health and life than invasive cancers. Superficial tumors can be treated with cutting (resecting) with an instrument placed in the urinary passage. However, even when the tumors are totally eradicated, there is a very high incidence of new tumors growing in the bladder. Therefore, every patient with a history of superficial bladder cancer requires follow up visits to detect new tumors. The manner of detection utilizes cystoscopy, the examination of the inside of the bladder with a fiberoptic lens passed through the urethra. If necessary a biopsy can be performed of abnormal areas through this Instrument. Certain characteristics of the Initial tumor suggest an increasing likelihood for tumors to reoccur as well as new tumors to invade the muscle of the bladder. The characteristics include: grade, invasion of the lamina propria, number of tumors at the initial time of diagnosis and the presence of carcinoma in situ. If one or more of the characteristics are present, we may advise additional treatment to the bladder after tumor resection.
B- Invasive tumors: lesions that invade the muscle layer (T2 an higher).
Bladder cancer can be also divided by histopathology (the diseased cell type) into:
Transitional cell carcinoma: Approximately 90% of bladder cancer.
Non transitional cell carcinoma:
Adenocarcinoma: account for less than 2% of bladder cancer.
Squamous cell carcinoma: accounts for 5-10% of bladder cancer.
Undifferentiated carcinomas: rare less than 2%.
Mixed carcinoma: 4-6%.
THE TUMOR GRADE:
The pathologist utilizing a bladder biopsy determines the tumor grade. The grade gives us an idea of how fast the cancer might be growing or how aggressive it might be. High-grade cancers grow faster and spread earlier than low-grade
cancers. The current system of grading uses only three different grades: well differentiated, moderately differentiated, and poorly differentiated (or Grade I, II, or III).
THE TUMOR STAGE:
The tumor stage is determined by the size and location of the cancer (The extent of the cancer within the bladder, and if it has spread to tissues around the bladder, or to other parts of the body). Usually initial staging studies include the pathology report from the initial biopsy, the general physical examination and digital rectal examination, and imaging of the upper urinary tract. Imaging studies include, Intravenous pyelograms (IVP), kidney ultrasounds, CT scans (Computerized Tomography), or MRI’s (Magnetic Resonance Imaging). The stage of the cancer is the most important deciding factor in which treatment will be used. The most accurate and the latest staging system is the TNM system. The letter (T) describes the bladder; the letter (N) describes the lymph nodes, and distant spread by the letter (M). A describing number (T2aN0M0) follows each letter:
T- Bladder
TX: Primary tumor cannot be assessed.
T0: No evidence of primary tumor.
Ta: Noninvasive papillary carcinoma.
TIS: Carcinoma in situ: “flat tumor“.
T1: Tumor invades subepithelial connective tissue.
T2: Tumor invades muscle:
T2a: Tumor invades superficial muscle (inner half).
T2b: Tumor invades deep muscle (outer half).
T3: Tumor invades perivesical tissue:
T3a: microscopically.
T3b: macroscopically (extravesical mass).
T4: Tumor invades any of the following:
Prostate, uterus, vagina, pelvic wall, abdominal wall.
N-Regional Lymph Nodes
NX: Regional lymph nodes cannot be assessed.
N0: No regional lymph node metastasis.
N1: Metastasis in a single lymph node 2 cm or less in greatest dimension.
N2: Metastasis in a single lymph node more than 2 cm but not more than 5 cm in greatest dimension, or multiple lymph nodes no more than 5 cm in greatest dimension.
N3: Metastasis in a lymph node more than 5 cm in greatest dimension.
M-Distant Metastasis
MX: Distant metastasis cannot be assessed.
M0: No distant metastasis.
M1: Distant metastasis.
THE DIAGNOSIS:
1- Signs and symptoms:
A patient may have bladder cancer for several months without realizing it. Sometimes symptoms such as urgency, frequency or burning/pain on urination occur, but often the patient has no complaints except for blood in the urine. All patients with either gross blood in the urine (the blood in the urine that you can see with your eye), or microscopic blood in the urine (the blood in the urine that needs a microscope to be seen and usually discovered during lab work) should be evaluated by a urologist, Blood in the urine can be a signal of a bladder cancer, but it can be caused also by infection, benign tumor, kidney stone, and other kidney diseases.
2- Bimanual abdominal and rectal examination:
By doing this examination the urologist may feel the tumor as a hardened spot in the bladder wall.
3- Lab findings:
Routine urine analysis: as a part of the bladder cancer diagnostic work up usually detects the most common laboratory abnormality, which is hematuria (blood in urine).
Urine cytology: cancer cells can be identified in voided urine and in the solution that used during cystoscopy to irrigate the bladder.
DNA Cytometry: cancer cells’ DNA can be assessed by either flow or image Cytometry. The test looks at the number of chromosomes in the cancer cells, which sometimes have abnormal numbers.
BTA test: Urine test that detects the presence of certain proteins secreted by bladder cancer cells.
Biomarkers: The Food and Drug Administration has recently approved a new urinary biomarker, Nuclear Matrix Protein 22 (NMP22), as an aid in the diagnosis of recurrent bladder cancer following surgical treatment. Nuclear Matrix Proteins are releases into the urine in patients with bladder cancer making them suitable targets for detection. A single voided urine specimen is obtained and sent to one of many major commercial laboratories where an immunoassay is utilized to help identify patients at risk for recurrent bladder cancer. A recent presentation by Dr. Sawczuk at the Annual Meeting of the Now York Section of Urology In Prague, Czech Republic, stressed the potential utility and clinical applicability of NMP22 in determining the frequency of cystoscopic evaluation with the possibility of biopsy in patients at risk for cancer recurrence. At the Cancer Detection and Prevention meeting held in Nice, France this October, Dr. Sawczuk spoke of the detection and monitoring abilities of NMP22. Evaluations of NMP22 as a biomarker in the monitoring of patients with bladder cancer continue at the Columbia- Presbyterian Medical Center. Among the most well studied biomarkers is P53. In several studies, overexpression of p53 correlated with progression of both stage Ta and T1 bladder cancer and might prove to be a helpful clinical adjunct. A number of other biological markers are under study.
4- Imaging:
Intravenous Pyelogram (IVP): an X ray of the urinary tract is taken after injection of a small amount of a special dye. It is used for the evaluation of the source hematuria, the upper urinary tract, and to assess the depth of invasive bladder tumors.
Abdominal or endovesical (inside the bladder) ultrasound: the bladder examined when full, and the bladder tumors may appear like intraluminal projections or like bladder wall infiltration.
Computed Tomography (CT), and Magnetic resonance imaging (MRI): can differentiate between bladder-confined disease and the tumor extension outside the bladder. It is also used to assess the extent of bladder wall invasion, and to detect the spread to pelvic lymph nodes.
5- Cystoscopy and tumor biopsy:
Cystoscopy allows the urologist to actually look inside the bladder, and look for any abnormalities. It is still the most reliable diagnostic tool. When coupled with biopsy, the diagnosis and initial staging of bladder cancer is made, and the results are the standard to which other noninvasive tests are compared. Many prognostic criteria (findings that affect the fate of the disease) like, the site of tumor, size, number of tumors, and whether the tumor is papillary can be assessed during cystoscopy. Cystoscopy is commonly performed with flexible instruments with the patient given local anesthesia. The presence of any suspicious lesions should prompt the urologist to schedule a formal biopsy and bimanual examination in the operating room to confirm the diagnosis and obtain valuable staging and pathologic information.
THE TREATMENT:
A-Transurethral Resection (TUR):
Surgery alone or combined with other therapies is used to treat more than 90% of bladder cancer patients. The standard initial therapy for TCC of the bladder is TUR, performed with either electrical or laser energy to treat non-invasive bladder cancer.
B- Partial Cystectomy:
Patients with invasive disease (that which invaded the muscle wall of the bladder), and patients who have had superficial bladder cancer and, despite treatment they continue to have tumor recurrence are at high risk of tumor spread to other parts of the body. Surgical removal of part of the bladder is the treatment of choice for these patients if the disease is in a limited part of the bladder wall.
C- Radical Cystectomy:
Surgical removal of the bladder in patients with more advanced disease. In The advent of nerve sparing, continent neobladder reconstruction techniques has increased interest in radical cystectomy as a definitive treatment for high-risk patients. The results of radical cystectomy in the management of high-grade lesions indicate 80%-90% 5-year survival rates. Biological markers such as p53 may help to identify patients destined to progress so that earlier aggressive treatment may be employed in such patients.
D- Intravesical therapy (Into the bladder):
It is used to treat superficial bladder cancer. Intravesical therapy has been used to eradicate existing tumors and prevent recurrence. Not all patients with superficial bladder cancer require Intravesical therapy. The urologist decides who are the patients that at high risk for recurrence or progression, who might need this treatment as an adjuvant to surgical treatment. Immuno- or chemotheraputic agents can be instilled into the bladder directly.
1-Intravesical Chemotherapy:
Chemotherapeutic agents in common use include thiotepa, mitomycin C, doxorubicin hydrochloride, and epirubicin.
2-Intravesical Immunotherapy with Bacillus Calmette-Guerin (BCG):
The live attenuated tuberculosis vaccine BCG was noted as early as 1929 to have anti cancer effects. Its efficacy far outweighs its potential side effects. Although most patients complain of local symptoms, such as dysuria or bladder-related symptoms, these effects do not significantly affect quality of life.
E- Other therapies:
Like Interferon, Intravesical Gene Therapy, Photodynamic Therapy, and Oral Therapy (Bropirimine and Vitamins).
THE FOLLOW-UP:
Follow-up depends on the stage and type of disease that is being treated. The Columbia-Presbyterian Medical Center follow-up plan recommended for patients with superficial TCC includes cystoscopy and urine cytologic studies every 3 or 4 months for 2 years, every 6 months for another 2 years, and yearly there after.
THE EXPECTED SURVIVAL TIMES:
The outlook for patients for early-stage bladder cancer that has not invaded the bladder wall is very good. About 90% of those patients live for five or more years with localized diagnosis and treatment.
THE PREVENTION AND DETECTION:
Bladder cancer often starts as a superficial cancer and with the passage of time, new bladder tumors may become invasive and life threatening. Early detection of bladder cancer and early treatment is essential for the prevention of recurrent superficial tumors, carcinoma in situ and recurrent tumors that invade the wall of the bladder. You should see a urologist as soon as possible if you have microscopic blood in the urine, blood visible without a microscope in the urine, recurrent UTIs, or voiding symptoms not improving. Further preventative measures include stopping cigarette smoking and yearly urine monitoring if there is a history of chemical exposure.
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