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Bladder Cancer

More than 60,000 new cases of bladder cancer are diagnosed each year in the United States. It is the 4th most common cancer in men and the eighth most common in women, and the 8th and 10th leading cause of cancer deaths, respectively.   The majority newly diagnosed bladder cancer patients will have superficial (non-invasive disease).  However, approximately 25% of these patients will have muscle-invasive bladder cancer at time of diagnosis. Moreover, of those who initially present with superficial disease, more than 10% will progress to invasive disease.       

When treated early and appropriately, most bladder cancers (even muscle-invasive) are potentially curable.  Still, some patients with aggressive bladder cancer will ultimately die of their cancer.  A coordinated individualized treatment approach is needed for each patient and close communication between a patient and his or her urologist is crucial.  Moreover, it is important to seek the care of a urologist with expertise in bladder cancer, as the treatment options can be quite variable and complex.

There are three main types of bladder cancer: transitional cell, squamous cell, and adenocarcinomas. Transitional cell carcinoma is the most common and accounts for almost 90 percent of all bladder cancers in the United States. Most cases of transitional cell carcinoma occur later in life. The cause of transitional cell carcinoma is unknown, but those who smoke or work in the textile, rubber, and dye industries have the greatest risk of acquiring the disease. For those who both smoke and experience chemical exposure in the workplace, the risk is greatly increased.

Generally there are two types of transitional cell carcinoma—superficial and invasive—the difference depending on whether the tumor has grown into, or invaded, the layers underneath the bladder lining. Bladder cancer staging, treatment and prognosis depend on how deeply it has invaded the organ. At diagnosis, 75% of tumors are superficial (involving only the mucosal surface of the bladder that is in contact with urine). Most of these tumors are at low risk of progression and metastasis and can be treated with repeated resections of just the tumor, sometimes with the addition of chemotherapy instilled directly into the bladder. Still, approximately to 25% of bladder cancers present with disease invading the muscular layers of the bladder. The therapy that offers the best chance for survival for these patients is complete removal of the bladder and surrounding lymph nodes (radical cystectomy and extended lymph node dissection).  Sometimes chemotherapy is used after surgery.  For cases in which extensive spread of the cancer is suspected, chemotherapy might be used first with surgery as a secondary therapy.

Nearly all squamous and adenocarcinomas of the bladder are invasive at the time of diagnosis. And can carry a worse prognosis than transitional cell bladder cancers, even with aggressive surgical therapy and chemotherapy.

Risk Factors

The leading risk factor for bladder cancer is smoking, including second hand smoke.

Occupational exposures to chemicals containing hydrocarbons or arylamines also increase the risk of developing bladder cancer. Occupations with high exposure to these carcinogens include the dye, rubber, leather, painting and aluminum industry. Other risk factors include certain chemotherapeutic agents, in particular cyclophosphamide. The use of hair dyes particularly in hair dressers has also been suggested as a risk factor for bladder cancer.

Staging of Bladder Cancer

Bladder cancer staging and treatment relies depends on the aggressiveness and depth of tumor invasion at the time of diagnosis, during a surgical procedure known as a transurethral resection of the bladder tumor (TURBT).  In this operation, a telescope (or cystoscope) is placed into the bladder and is used to remove tumor tissue. Treatment decisions are heavily based on the aggressiveness of the tumor (pathologic grade) and the layer of the bladder that is involved with the tumor (pathologic stage). It is important to obtain a sample of the muscle of the bladder at the base of the tumor in order to determine whether the tumor has invaded the muscular layer.

“Superficial” or non-invasive bladder tumors arise from the mucosal layer of the bladder wall and are usually completely removed (resected) during a TURBT. Tumors that have invaded the thin layer of connective tissue just deep to the mucosal layer called the lamina propria (stage T1), require special attention, since up to 30% may have evidence of muscle invasion on re-resection. If there is adequate muscle present in the pathology specimen to ascertain the absence of muscle invasion, these tumors can be treated with the instillation of chemotherapy or immunologic agents directly into the bladder.

Invasive tumors are those that invade into the bladder muscle.  Treatment options for such muscle-invasive bladder are more aggressive than for non-invasive/superficial disease. Radical cystectomy remains the gold standard of care for muscle invasive bladder cancer. In this operation, the bladder is removed. Cystectomy provides accurate pathological staging of the primary bladder tumor and the regional lymph nodes, offers the best local disease control and long-term disease-free survival, and it provides accurate risk assessment and identifies those patients who might benefit from additional (or adjuvant) therapy.  For those patients in whom the cancer has already spread at the time of diagnosis, surgery is used primarily to eliminate symptoms of the disease. Chemotherapy is generally used as a primary treatment.  In addition, chemotherapy and/or radiation therapy is reserved for patients who are not candidates for surgery.

Surgical Treatment

Surgical removal of the bladder (radical cystectomy) is the most effective treatment for bladder cancer that has invaded the muscle wall of the bladder. Therefore, radical cystectomy with bilateral pelvic and iliac lymphadenectomy is a standard treatment for high-grade, invasive bladder cancer.  Improvements and advancements in surgical techniques and post-operative care has greatly reduced the side effects of bladder removal and increased the effectiveness of the operation. Recurrence-free and overall survival after cystectomy depends on the pathological stage. Patients who have lymph node negative, organ confined cancer have a 5 year survival of ~80% whereas patients with disease extending outside the bladder or into the lymph node involvement have 5 year survival rates of ≤50%. Remarkably, patients with lymph node involvement still have an approximately 35% chance of long term survival with a radical cystectomy and extended pelvic lymph node dissection.

In men radical cystectomy involves complete removal of the bladder, prostate, seminal vesicles and pelvic lymph nodes. In female patients a radical cystectomy (referred to as anterior exenteration), traditionally involves removal of the bladder, uterus, fallopian tubes, ovaries, and the anterior vaginal wall. While this is still necessary in some patients, the pelvic organs and the vagina can sometimes be spared in certain female patients without compromising cancer control. Cystectomy provides the best survival outcomes and the lowest local recurrence rates for muscle-invasive disease.

Patients undergoing bladder removal have several options for “reconstruction of the urinary tract.” The ileal conduit is the oldest method.  The conduit is constructed from a small segment of the intestine and is brought out to the skin as a stoma so that the urine drains into a bag. There are alternatives to the ileal conduit.   Orthotopic neobladders also use intestine, but it is used to construct the bladder substitute. The bowel segment is refashioned in a spherical shape, replacing the bladder. This pouch is then connected to the urethra, so the patient can void through the urethra. This form of urinary diversion is used successfully in men and women undergoing radical cystectomy. For those patients who are not candidates for the orthotopic neobladder (due to injury to or cancer in the urethra or incontinence, for example) and who do not wish to have an external collecting device or appliance (like the ileal conduit) may have an internal reservoir constructed from the colon with a continent catheterizable stoma.  This is called a continent cutaneous diversion. The patient voids by inserting a catheter into the stoma to empty the urine every 4-6 hours. The one-way valve mechanism allows for catheterization through the small stoma on the abdominal wall (often buried in the umbilicus), enabling the reservoir to empty; however, this limb remains continent during the storage phase between catheterizations.  We recommend a lengthy conversation between a physician and patient to determine which method of reconstruction is best for each individual patient.

Robot assisted laparoscopic radical cystectomy is also being offered as an alternative to open surgery. In addition, it is now possible for some men and women to maintain their sexual function following bladder removal. These ongoing advances in the surgical treatment of bladder cancer allow patients the best chance of being cured of their disease and yet able to enjoy an excellent quality of life following surgery.

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