Urinary system cancers

ALSO KNOWN AS: Bladder cancer, kidney and renal pelvic cancer, renal cell carcinoma, cancer of the urothelium, transitional cell cancer of the renal pelvis and ureter, urethral cancer, urethral neoplasms, squamous cell carcinoma of the urethra

RELATED CONDITIONS: Birt-Hogg-Dubé syndrome, von Hippel–Lindau disease, hereditary leiomyomatosis

DEFINITION: Urinary system cancers are malignancies occurring anywhere in the organs of the urinary tract, including the kidney, ureter, bladder, and urethra. The kidney removes wastes and water from the blood, creating urine, which collects in the renal pelvis in the kidney. A ureter tube carries the urine to the bladder, which stores urine. Typically, the bladder is flat when empty, and balloons when full with urine, triggering the urge to urinate. The urethra, another tube, carries urine from the bladder to the outside of the body. Nine out of ten kidney cancers are renal cell carcinomas. Cancers that form in the renal pelvis and ureters develop from transitional cells. Some 98 percent of bladder tumors occur in the transitional cells that line the bladder. Urethral cancers are most commonly squamous cell cancers, followed by transitional cell cancers.

Risk factors: Risk factors vary by type of urinary tract cancer. Risk factors for kidney cancer include cigarette smoking (40 percent greater risk), obesity, high blood pressure, long-term dialysis, and occupational exposure to carcinogens such as asbestos, benzene, cadmium, herbicides, and organic solvents. Several hereditary disorders increase the risk of kidney cancervon Hippel-Lindau (VHL) disease (about 25 percent of those afflicted develop clear-cell renal carcinoma), hereditary papillary renal cell carcinoma, Birt-Hogg-Dubé syndrome, hereditary leiomyomatosis, and hereditary renal oncocytoma. People with these conditions or prior renal cell carcinoma should be evaluated frequently. Renal cancer affects more men than women, partly because men are more likely to smoke cigarettes and be exposed to occupational carcinogens.

Cigarette smokers have two to three times the risk of developing bladder cancer than nonsmokers. Smokers account for 50 percent of bladder cancers. Other risk factors implicated in the development of bladder cancer are occupational exposure to benzene or benzidene (20 to 25 percent of cases), a high-fat diet, excessive use of drugs containing the pain reliever phenacetin, and infection from Schistosoma haematobium, a type of fluke endemic in Europe, North America, and regions of northern Africa. There has also been an association found between chlorinated drinking water and the incidence of bladder cancer.

A history of bladder cancer and being over sixty are major risk factors for urethral cancer. Some studies indicate chronic urinary tract infections and irritation cause urethral cancer cell growth. A history of sexually transmitted infections, particularly the human papillomavirus (HPV), has also been associated with an increased risk.

Etiology and the disease process: The causes of urinary tract cancers are uncertain, although many cases are found in active or past cigarette smokers. Renal cell carcinomas are primarily clear-cell type (80 percent), followed by papillary renal carcinoma (10 to 15 percent). The clear-cell type has cells that look very pale under a microscope, while finger-like projections characterize the papillary type.

The bladder wall is lined with transitional cells and squamous cells. More than 90 percent of bladder cancers begin in transitional cells and 8 percent in squamous cells. Cancer occurring only in cells that line the bladder is referred to as superficial bladder cancer (carcinoma in situ). Cancers that begin in the transitional cells may spread through the bladder’s lining and into the bladder's muscular wall. In women, this type of bladder cancer may invade adjacent organs like the vagina or uterus. In men, it may invade the prostate gland. In either gender, it may spread to the wall of the abdomen. When the cancer spreads outside the bladder, nearby lymph nodes are often involved. Distant disease may develop when a primary bladder cancer spreads to another part of the body.

Most urethral cancers invade locally but are aggressive, metastasizing to nearby tissue. Often, they are locally advanced by the time of diagnosis. However, most urethral cancers do not spread distally. Cancer of the urethra manifests differently in men and women, differing in the type of cancer cells involved—squamous cell, transitional cell, or adenocarcinoma.

Incidence: The median age of diagnosis for cancer of the kidney and renal pelvis is sixty-four years. Renal cell carcinoma accounts for approximately 70 percent of kidney cancers and renal pelvis cancers for about 15 percent. The incidence rate for kidney cancer is approximately 15.5 new cases per 100,000 people per year. The incidence rate in men is approximately twice that in women across ethnic groups, with the highest incidence in black men, an estimated rate of 24.7 cases per 100,000 population.

Bladder cancer is the most common type of malignancy affecting the urinary system. Over 600,000 new cases are diagnosed globally each year. The United States's overall incidence rate is around 18 per 100,000 people. The incidence is higher in men than women and approximately twice as high in White men than Black or Hispanic men. Nearly three-quarters of all cases of bladder cancer occur in individuals over sixty-five.

Urethral cancer usually develops in the squamous cells that line the urethra. Most urethral cancer in women occurs in the labia, vagina, or bladder neck. In men, it occurs in the vascular spaces of the corpora and periurethral tissue, deep tissue in the perineum, urogenital diaphragm, prostate, or penile and scrotal skin. Urethral cancer is a very rare condition, accounting for less than 1 percent of all cancer cases. It is the only genitourinary system cancer that has a greater incidence in women than in men. The most common urethral cancer is squamous cell carcinoma, followed by transitional cell carcinoma and then adenocarcinoma.

Symptoms: People with urinary tract cancer often experience hematuria, or blood in the urine, which is usually visible to the naked eye or upon inspection under a microscope. A thorough diagnostic evaluation following a finding of hematuria is essential to eliminate other conditions, such as kidney stones or a urinary tract infection.

Patients with renal cell carcinoma may complain of hematuria, pain in the side, an abdominal lump, anemia, loss of appetite, and unexplained weight loss. Symptoms of transitional cell cancer of the renal pelvis and ureters include hematuria, back pain, fatigue, unexplained weight loss, frequent urination, or pain on urination. Common symptoms of bladder cancer include hematuria, lower back pain, frequent urination, and pain during urination. Patients with urethral cancer may have no symptoms early on or may experience hematuria, trouble with urinary flow (such as interrupted flow), a discharge, a lump or thickness in the penis or perineum, and enlarged lymph nodes in the groin area.

Screening and diagnosis: No standard screening tests for urinary tract cancers exist. Often, kidney cancer is detected during a physical examination conducted for another purpose. When a person complains of symptoms consistent with urinary system cancer, the physician performs a complete physical exam, feeling the abdomen for masses or abnormalities. They take a medical history and ask about risk factors like smoking and occupational exposure to carcinogens.

The physician orders blood and urine tests if the patient complains of hematuria. A urine cytology test reveals markers associated with cancer cells or cancer cells coming from the bladder's lining. A cystoscopy, in which a cystoscope (lighted tube) is inserted into the bladder through the urethra, checks for areas to biopsy. (If the scope is extended into the ureter and renal pelvis, the test is called a ureteroscopy.) Another tool is an intravenous pyelogram (IVP), in which a contrast dye is injected into a vein, and a series of X-rays is taken to look for blockages in the kidney, ureter, and bladder. If cancer is detected, imaging studies such as computed tomography (CT) scans, magnetic resonance imaging (MRI), or ultrasound may be used to assess tumor growth and spread and to stage the cancer.

Urinary system cancers follow various staging systems. Most systems divide cancers into stages according to the size of the tumor and its extent of spread (localized, regional, or distant areas of the body). Many systems also grade the tumor, depending on how aggressively the cancer is growing.

Treatment and therapy: Surgery, radiation therapy, chemotherapy, and biological therapy are typical treatment options for urinary system cancers.

In renal cell carcinoma, surgery is the common option. A partial nephrectomy removes the tumor in the kidney and some tissue with it; a simple nephrectomy removes only the kidney; and a removes the kidney, surrounding tissue, adrenal gland, and lymph nodes. A radical nephrectomy may be more likely to cure the cancer in individuals with stage 2 or stage 3 tumors. Patients sometimes receive radiation therapy or after surgery to remove any remaining cancerous cells. Minimally invasive surgeries such as laparoscopy can be used for partial or radical nephrectomies. The use of laparoscopy reduces blood loss during surgery, requires less use of narcotics for pain, and shortens hospital stays and recovery time.

Surgery is uncommon for stage 4 renal cell cancers since they cannot be cured. In these cases, a technique called arterial embolization is appropriate. Gelatin sponges block blood flow to the kidney and kill the cancerous cells. Targeted chemotherapies such as sorafenib, sunitinib, and temsirolimus are helpful. Patients at this stage in otherwise good health may tolerate the side effects associated with interleukin 2 (IL-2) or cytokine therapy. The patient’s physician may recommend that the kidney be removed before starting this therapy to enhance the response to treatment.

For transitional cell cancer of the renal pelvis and ureter, standard surgical options include removing part of the ureter (in superficial cases) or a nephroureterectomy, which removes the kidney, ureter, and the tissue that connects the ureter to the bladder.

For bladder cancer, standard treatment includes surgery, radiation therapy, chemotherapy, and biological therapy. Surgical options include transurethral resection (TUR) with fulguration, in which high-energy electricity burns away cancerous areas during a cytoscopy; a segmental cystectomy, in which part of the bladder is removed; and a radical cystectomy, in which the bladder, lymph nodes, and nearby organs (prostate and seminal vesicles in men; uterus, ovaries, and part of the vagina in women) are removed. If the bladder is removed, the surgeon creates another outlet where urine is stored and leaves the body, referred to as a urinary diversion. Chemotherapy or radiation therapy may be performed following surgery to eliminate remaining cancer cells or stunt their growth.

In cases of bladder cancer, radiation therapy is used externally and internally through radioactive seeds placed in the body near the cancer. Chemotherapy is delivered orally or by injection, placed directly in an affected area, or delivered through a tube inserted into the bladder. Biological therapy may be used to bolster an affected individual’s immune system to fight the cancer.

The standard treatments for urethral cancer are surgery, radiation therapy, and watchful waiting. Surgery may remove the cancer by excision, burning with high-energy electricity (electroresection with fulguration), or laser surgery. Depending on the cancer’s spread, other surgeries performed include lymph-node dissection (removal of lymph nodes in groin and pelvis), (removal of bladder and urethra), (removal of bladder and prostate), anterior exenteration (removal of urethra, bladder, and vagina), partial (removal of part of penis near urethra), and radical penectomy (removal of entire penis).

External and internal radiation therapy are also used for urethral cancer. Some patients are simply monitored for signs that the cancer has developed to the point where further treatment is necessary.

Patients should consult their physician regarding treatment options, including those in clinical trials. Decisions should be based on the stage and grade of cancer, the patient’s age and overall health, and the expected following treatment.

Prognosis, prevention, and outcomes: Outcomes experienced by those with urinary system cancers depend on many factors, including the stage of their cancers, whether they are superficial or invasive, the degree of metastasis, and the patient’s overall health and age. Around one-third of renal cell cancers and more than half of renal pelvic and ureter cancers could be eliminated if people stopped smoking cigarettes.

The overall five-year relative survival rate for kidney and renal cell cancers is 76.5 percent; for bladder cancer, 71 percent; for ureteral cancer, 46 percent; and for urethral cancer, about 46 percent.

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