Her lungs — that’s what Elena* worried about most. She told the nurse practitioner that the fumes from the dyes and chemicals she’d worked with during 37 years as a factory worker must have done some damage, not to mention her pack-a-day cigarette habit. At age 16, Elena started out smoking her father’s Camels. She switched to filters eight years later when she found a steady job in the factory.

The urinary frequency and burning that brought the 57-year-old to the clinic were more an annoyance than a worry. She was surprised when the urine culture the NP ordered showed no infection, and she was downright shocked when the NP ordered a urine cytology to test for malignant cells. Like many men and women, Elena had never heard of the connection between bladder cancer and smoking or exposure to certain chemicals.

Malignant cells showed up on the cytology, and the subsequent cytoscopy revealed a bladder mass. In a matter of days, Elena was on her way to the OR for a transurethral resection of her bladder tumor (TURBT), a procedure to resect bladder tumors for tissue diagnosis. Elena’s diagnosis — transitional cell carcinoma of the bladder.

Bladder cancer is the fourth most common cancer in men and 10th in women. An estimated 61,420 new cases of bladder cancer — 44,690 in men and 16,730 in women — were predicted for 2006. The predicted mortality for 2006 was 13,060 (8,990 men, 4,070 women).¹ The majority of bladder cancers occur in people over the age of 60. The ratio of bladder cancer in U.S. men and women is about 3 to 1.2

Most bladder cancer can be linked to environmental exposures to carcinogens. The epithelial lining of the bladder is constantly exposed to potential carcinogens as they are excreted in the urine. Carcinogens encountered in occupational settings include aromatic amines (rubber, textile, dye, and chemical industries); chemicals used in aluminum, paint, and petroleum industries; diesel exhaust, and hair dye.²

Arsenic in drinking water has been implicated in an increased risk of bladder cancer. Exposure to artificial sweeteners has been linked to bladder cancer in animal studies but has not been definitively linked with humans. Other possible associations include genetic factors, chronic cystitis, exposure to chemotherapy agents (especially alkylating agents), radiation exposure, and schistosomiasis.²

Cigarette smoking is a major risk factor. Although the relative risk posed by smoking is less than occupational exposure, the prevalence of cigarette smoking makes it the most important (and preventable) risk factor. The risk of bladder cancer is related to the amount and length of time of exposure. Heavy, long-term smokers can have a six to 10 times higher risk than nonsmokers. Smoking cessation greatly reduces the risk of bladder cancer, but the risk for smokers who quit remains higher than that of nonsmokers. Cigarette smoke contains many carcinogens, many of which are excreted in urine.² Interestingly, cigar smoking, pipe smoking, and chewing tobacco have not been linked to bladder cancer.

The urinary bladder

The bladder is comprised of four layers. The innermost layer is the urothelium, a thin layer of epithelial tissue. The next layer is the lamina propria, part connective tissue and part smooth muscle. The lamina propria contains vascular and nerve structures. It is separated from the urothelium by a basement membrane. The third layer is the muscularis propria or the detrusor muscle. The outermost layer is called the adventitia or serosal layer, and it separates the bladder from surrounding tissues.³

Clinical presentation

Gross hematuria is the most common presenting symptom. The hematuria is usually intermittent, painless, and present throughout micturition. Other presenting symptoms may include microscopic hematuria; voiding symptoms, such as frequency and nocturia and pain; and constitutional symptoms, such as fatigue, weight loss, and anorexia. Pain and constitutional symptoms are usually associated with advanced disease. Clinicians should evaluate hematuria to rule out other conditions, such as urinary tract infection, prostatitis, and kidney stones. The diagnosis of bladder cancer is often delayed because of the similarity of symptoms to benign disorders and because the symptoms are often intermittent. There is a difference in morbidity and mortality between early stage and late stage disease, and unexplained hematuria should always be investigated.⁴

Diagnostic tests

Early intervention when hematuria is detected is essential in the diagnosis of bladder cancer. A thorough work-up including a urine culture and cytology is needed. A culture identifies infection; cytology detects malignant cells. Based on these findings and clinical symptoms, the physician will perform a cystoscopy.

In cystoscopy, a physician visualizes the interior of the bladder and urethra via a cystoscope. This can be done in a physician office under local anesthetic or in an outpatient surgical center under general or spinal anesthesia. If a suspicious lesion is present, a biopsy or transurethral resection of the bladder tumor is done. During a TURBT, the surgeon attempts to remove all visible lesions. This can also be a method for obtaining a biopsy specimen if the lesion is relatively small and superficial.⁴

Radiology imaging evaluates the extent of disease. Excretory urography or intravenous pyelogram (IVP) evaluates the upper tracts for associated tumors in the kidneys and ureters. A renal ultrasound may also be used. CT scans are performed to evaluate the extent of disease to the surrounding abdomen/pelvis and lymph nodes. MRI may also be used for staging the disease.^4,5

Staging

The TNM Bladder Classification System, developed by the American Joint Committee on Cancer, is generally used for bladder cancer. It evaluates the depth of primary tumor (the T in TNM), regional lymph node (N) involvement, and distant metastasis (M). Clinicians should have a clear understanding of this staging system to plan treatment.

Bladder cancer is divided into superficial and muscle-invasive disease. Superficial disease consists of Ta tumors (noninvasive papillary tumors), carcinoma in situ (CIS or Tis, tumor in situ), and T1 tumors (which invade the lamina propria). Ta and Tis tumors are Stage 0. T1 tumors are Stage 1. Muscle-invasive disease consists of T2 and higher. About 90% to 95% of tumors are transitional cell carcinoma; the remaining are composed of 3% squamous cell carcinoma, 2% adenocarcinoma, and 1% small cell carcinoma.⁴ T2 tumors are Stage 2; T3 tumors invade the fatty tissue outside the bladder and are Stage 3. Stage 3 disease also includes T4a, which is tumor that invades local structures outside the bladder, such as the prostate for men and the uterus in women. Stage 4 disease includes any T that also has positive lymph nodes or metastasis.^4,6

Knowing the grade of disease is important. Bladder cancer can be given one of three grades. Grade 1 is a cancer that looks somewhat like normal bladder tissue under a microscope. Grade 2 disease is an intermediate grade. Grade 3 is a tumor that looks very abnormal. The higher the grade, the more aggressive the tumor. High-grade disease is more likely to be invasive.^5,6

Treatment

Treatment for bladder cancer depends upon the cell type, the stage of disease, and the grade of disease. For superficial bladder cancer, the standard treatment is a TURBT, usually done at the time of diagnosis. After resection, the surgical pathology will reveal the type of superficial bladder cancer, Ta, T1, or CIS. About 70% of newly diagnosed cases are superficial disease. An estimated 40% to 80% of these will have a recurrence or new occurrence within five years, and 10% to 25% will progress to muscle-invasive disease. Superficial bladder cancers can have distinguishing features that make them high risk. These include more than three bladder lesions, lesions greater than 3 cm in diameter, a T1 tumor that invades the lamina propria, Grade 3 tumor, incomplete resection due to extent of tumor or location of tumor, and the presence of diffuse Tis.⁸

Because superficial disease has a high recurrence rate, once the tumor has been thoroughly resected by TURBT, patients are closely monitored every three months using surveillance cystoscopies and cytology for at least five years after diagnosis.⁸

Some patients need treatment beyond TURBT, depending on the stage and grade of the disease and other high-risk features, such as lymphovascular invasion. Intravesical therapy is the instillation of chemotherapy or an immunological agent directly into the bladder via catheterization. The indications for intravesical therapy include as prophylaxis treatment to prevent recurrence of disease or as adjuvant treatment to treat residual disease that remains after a TURBT. Intravesical therapy is commonly used to treat diffuse CIS. To date, bacilli Calmette-Guérin, an immunological agent, is the most effective treatment for CIS. Although the exact mechanism of action is unknown, BCG causes multiple local inflammatory effects that correlate with tumor response. BCG delays but does not prevent tumor progression; it reduces the need for a later cystectomy by increasing disease-free interval and prolonging disease control. The patient may die of other causes before the bladder cancer becomes a problem.⁸ The most common adverse effects are flulike symptoms (fever, bladder irritation, dysuria, urinary frequency, and infections) and, rarely, sepsis.^7,8 Patients may experience these symptoms for months and even years after treatment ends. So although BCG treatment is a simple outpatient treatment, it can have significant effects on patients’ quality of life. It is important to educate the patient to report any adverse effects, which may require modification of the BCG dose.

Other agents that can be used for intravesical instillation include doxorubicin hydrochloride (Adriamycin), mitomycin (Mitomycin C), interferon (IFN), thiotepa (Thioplex), and gemcitabine (Gemzar). In general, these agents are used when patients become refractory to BCG treatment, cannot tolerate the adverse effects of BCG, or have low-risk disease.⁷

The nurse needs to educate patients about intravesical agents, including the indications, contraindications, and expected/unexpected adverse effects that need to be reported to a clinician. Pretreatment instructions include the length of time the agent will remain in the bladder and the importance of withholding fluids or caffeinated products two to four hours beforehand. Withholding fluids will enable the patient to retain the agent in the bladder for the allotted time.

Treatment can be started about two weeks after a TURBT provided hematuria has resolved, and it is repeated weekly for six weeks. Before administration, the nurse assesses for signs and symptoms of dysuria, urinary tract infection, gross hematuria, and fever, and he or she reports any abnormalities to the physician. Treatment is withheld when appropriate and resumed when symptoms resolve.

Nurses performing intravesical therapy must be competent in catheterization. Catheterization must be atraumatic to prevent injury to the urethral mucosa, which could result in a systemic infection. After therapy is completed, the nurse should inform patients of the follow-up plan, which includes a cystoscopy to assess treatment response. If recurrence is present, a TURBT will be performed. If intravesical therapy is not effective or not tolerated, a radical cystectomy may be recommended based on surgical pathology.

The indications for more radical surgical approaches include recurrent or progressive disease that is resistant to intravesical therapy, high-grade tumors associated with CIS, a tumor that has invaded the muscularis propria, and bladder symptoms that cannot be managed medically, such as urinary frequency or hemorrhage. How extensive the surgery is depends upon the extent of disease. Any cystectomy is major surgery that can result in the loss of sexual function and includes the need for urinary diversion. If the tumor has potentially invaded surrounding structures, a wider surgery may be indicated. A radical cystectomy includes the removal of the bladder and part of the urethra. For women, this includes removal of the uterus, fallopian tubes, and part of the vagina. For men, it is removal of the prostate and seminal vesicles. This has a direct impact on sexuality for both sexes. In addition, at least 10 to 15 lymph nodes should be removed to evaluate whether metastatic disease is present. If required, an extended pelvic lymph node dissection is done. The complications of a cystectomy with urinary diversion can include rectal perforation, pelvic abscesses, intestinal obstruction, acute pyelonephritis, ureteral obstruction, stomal stenosis, intestinal fistula, renal calculus, hemorrhage, pulmonary or cardiac compromise, and wound infections.⁹

After the bladder is removed, incontinent or continent urinary pathways can be created to divert urine out of the body. An ileal conduit is an incontinent diversion formed by removing a section of the terminal ileum (small intestine). It is attached to the ureters and creates a conduit that diverts urine outside the body via a stoma created in the abdominal wall. An external appliance (urostomy bag) collects urine.⁵ When choosing an ileal conduit, one must consider alteration in body image, the impact on sexuality, and the ability of the patient to care for the ostomy appliance. Complications associated with a stoma may include improper fitting, a necrotic stoma, contact dermatitis, mechanical trauma, fungal infections, and skin lesions.

A continent urinary diversion is an internal pouch or reservoir where urine is collected and can be released by catheterizing through a stoma or the urethra. These continent diversions vary based on the surgical technique, the segment of intestine used to create the pouch, and the location of stoma or urethra. The advantage of a continent urinary diversion is that an external appliance is not required. Exclusion criteria for a continent urinary diversion can include GI conditions that would interfere with bowel resection (i.e., diverticular disease, ulcerative colitis, or irritable bowel syndrome); a history of pelvic radiation; and a lack of manual dexterity and motivation required for self-catheterization.

For some patients, bladder sparing surgery may be an option. In general, however, TURBT or partial cystectomy have inferior outcomes compared to a radical cystectomy. Limited surgery may be indicated for elderly patients or for those who might not able to tolerate the rigors of extensive surgery.⁹

For patients with locally advanced disease, additional treatment after a cystectomy is indicated. If there are positive surgical margins, postoperative radiation therapy is an option. The research to support postoperative RT is limited at this point. While RT may provide longer disease-free survival, the therapy must be weighed against potential complications of small bowel obstructions and fistulas.⁹

Chemotherapy can also be used in the treatment of locally advanced bladder cancer. Chemotherapy can be administered in one of two ways. Neoadjuvant therapy is given before surgery to try to reduce the size and extent of the tumor. Adjuvant therapy is administered postoperatively for surgically staged T3b and T4 disease in an attempt to reduce the possibility of recurrence. About 50% of patients with muscle-invasive disease who receive no further therapy develop metastatic disease within two years of surgery. The role of adjuvant chemotherapy has not been fully studied. Adjuvant chemotherapy has been found to delay recurrences, but improvement in the overall survival rate has not been definitively proven. Further clinical trials are being conducted.¹⁰

Neoadjuvant chemotherapy consists of cisplatin-based combinations. One combination includes methotrexate (Mexate), vinblastine (Velban), doxorubicin, and cisplatin (Platinol), known as MVAC. MVAC has been used for many years, but is associated with significant toxicities. A second protocol includes cisplatin and gemcitabine (Gemzar). The cisplatin/gemcitabine has been shown to be “not inferior” to MVAC but with a more favorable toxicity profile. Other combinations are being studied to try to find therapies equal to MVAC, but with fewer toxicities. These include cisplatin and paclitaxel, gemcitabine and paclitaxel, gemcitabine and docetaxel, and cisplatin and gemcitabine in combination with either paclitaxel or docetaxel.¹⁰

The adverse effects of chemotherapy vary, but certain toxicities are common to most agents. The most common is myelosuppression, a drop in white blood cell, red blood cell, and platelet count. Other adverse effects include fatigue, nausea, vomiting, and alopecia. Growth factors and antiemetics are used to alleviate toxicities. Cisplatin can cause renal toxicity; patients receiving cisplatin require aggressive hydration. Peripheral neuropathy is common with paclitaxel and cisplatin. The adverse effects of radiation include diarrhea, proctitis, and risk of adhesion formation.

Nurses must educate patients about adverse effects and their management throughout the spectrum of care. Patients must be taught to inform medical staff about any toxicities in order to avoid complications.

Several new bladder cancer tests are available. While their usefulness as diagnostic tools has not been established, they do appear to be useful for monitoring for disease recurrence. The advantage of these kits is that they use urine samples to identify different types of tumor markers. This provides a noninvasive way to monitor for recurrence. However, there are problems with false-positive readings, and they should be considered as one indicator only to monitor, not as a complete diagnostic tool. The problem of false-positive readings makes this type of testing ineffective as screening tools in the general population.^11,12 However, research continues to identify less invasive and more accurate screening and diagnostic tools.

Early detection and diagnosis of bladder cancer is vital for improved survival. Nurses need to keep up to date on bladder cancer and its treatment to fulfill the many different roles required to treat this disease, including direct patient care, education, coordination of services, and psychosocial support. Knowledgeable nurses have a positive impact on patient outcomes and quality of life.

*Not a real patient.