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Renal Cell Carcinoma (RCC)
Several types of cancer can afflict the kidneys. Renal cell carcinoma (RCC), the most common form, accounts for approximately 85% of all kidney cancers. In RCC, malignant (cancerous) cells develop in the lining of the kidney's tubules and typically grow into a mass called a tumor. Single tumors are the norm, although more than one tumor can develop within one or both kidneys.

Early diagnosis is critically important. As with most cancers, the earlier kidney tumors are discovered, the better a patient's chances for survival. Tumors discovered at an early stage often respond well to treatment. Survival rates in such cases are high. Tumors that have grown large or metastasized (spread) through the bloodstream or lymphatic system to other parts of the body are much more difficult to treat and present a greatly increased risk for mortality.

Incidence and Prevalence
It is important to realize that with timely diagnosis and treatment kidney cancer can be cured. If found early, the year survival rate for patients with kidney cancer ranges from 79% to 100%. More than 100,000 survivors of kidney cancer are alive in the United States today.

In the United States, renal adenocarcinoma —cancer of the kidney —accounts for about 3% of all adult cancers. About 30,000 new cases are diagnosed annually. The disease usually affects people between the ages of 50 and 70, and affects men almost twice as often as women.

The Kidneys
The kidneys are an essential part of the body's urinary system. Each kidney is composed of about one million microscopic "filtering packets" called glomeruli. The glomeruli remove uremic waste products from the blood. Each glomerulus connects to a long tube, called the tubule. Urine made by the glomerulus moves down the tubule. Together, the glomerulus and the tubule form a unit called a nephron. Each nephron connects to progressively larger tubular branches, until it reaches a large collection area called the calyx. The calices form the funnel-shaped portion of the upper ureter (renal pelvis). Urine moves from the renal pelvis to the ureters, the large tubes that connect the kidney to the bladder.

The kidneys produce three important hormones: erythropoitin (EPO), which triggers the production of red blood cells in bones; renin, which regulates blood pressure; and vitamin D, which helps regulate the body's metabolism of calcium necessary for healthy bones.

Diagnosis

If the physician suspects that symptoms are caused by RCC, the patient will undergo a series of examinations, procedures, and laboratory tests to confirm the diagnosis. The process usually starts with a thorough physical examination to assess the patient's health and to gather as much information as possible about his or her symptoms. A medical history is taken to determine if there are any risk factors associated with RCC.

Imaging
One or more imaging tests are performed to obtain pictures of the kidney(s) and any abnormalities that may be causing the symptoms. Several imaging procedures can produce these images. Most of these techniques are painless. A few require the injection of a special "tracer" material (dye or low-level radioactive isotope) into the patient's bloodstream.

Computed tomographic (CT) scan
A computer (CT or CAT scan) is a type of x-ray that produces a series of cross-sectional, three-dimensional images of internal organs and glands. It can detect tumors and, in some cases, lymph nodes enlarged by cancer.

Magnetic resonance imaging (MRI)
An MRI uses large magnets to project magnetic waves through the body and create computer-generated, cross-sectional images of internal organs.

Ultrasound
Ultrasound uses sound waves projected into the body to produce an image of internal organs, structures, and tumors. In this painless procedure, a gel is applied to the patient's pelvic and kidney areas, and a small device that emits ultrasonic pulses is slowly passed over the area. The sonic image thus produced is viewed on a monitor.

Intravenous pyelogram (IVP)
The doctor also may prescribe a procedure called an intravenous pyelogram (IVP), which involves injecting a dye containing iodine through a vein in the arm into the bloodstream. The dye eventually collects in the urinary system, where it improves the contrast for x-rays and produces a well-defined image of the kidneys, ureters, and bladder. By showing up as white on the dark x-ray film, the IVP can disclose a tumor or the damage caused by a tumor in the kidney.

In some cases, the physician may request an arteriogram or venacavagram (IVPs of the blood vessels that supply the kidneys) to look for tumors in the connecting arteries and veins.

Chest x-ray
If there is reason to believe RCC is present and has metastasized, the doctor may order a standard chest x-ray to see if it has spread to the lungs or bones in the chest.

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Bone scan
This nuclear imaging procedure is used to detect the spread (metastasis) of cancer to bones, when aggressive tumors and metastasis are suspected. In a bone scan, a small amount of low-level radioactive material is injected into a vein in the arm. This material discloses metastatic cancer, as well as some noncancerous diseases, in bones.

Laboratory tests
One or more laboratory tests are performed to confirm the presence of RCC.

Urinalysis
More than half of all patients with RCC have blood in their urine (called hematuria). Often this blood is present in such small amounts or so diffused in the urine that it cannot be seen with the naked eye (called microscopic hematuria). To detect hematuria a chemical test of the urine usually is prescribed. On occasion, cells found in the urine are examined under a microscope for abnormalities. This procedure is called urine cytology.

Blood tests
Another laboratory procedure typically used in the diagnosis of RCC involves microscopic examination and/or chemical analysis of the patient's blood. These tests screen for the following conditions which may indicate the presence of cancer:

• Anemia (too few red blood cells; caused by internal bleeding, a common cancer symptom)
• Polycythemia (too many red blood cells; sometimes caused by cancerous tumors in the kidney that trigger the release of erythropoitin, EPO, a hormone that increases red blood cell production in bone marrow)
• Hypercalcemia (high blood calcium levels)and elevated liver enzymes (conditions characteristic of RCC)

Cystoscopy
Blood in the urine can result from other health problems, such as kidney stones or traumatic kidney injury, so the doctor may order a cystoscopy to determine precisely where the internal bleeding is occurring. In cystoscopy, a long, thin, rigid or flexible optical scope is inserted through the urethra and into the bladder. The practitioner then makes a visual examination of the urethra, bladder, and kidneys to locate the site of bleeding.

Fine needle aspiration
RCC tumors are made up of malignant (cancerous) cells that grow into a mass. If a tumor is found through imaging or other procedures, a cell sample may be taken for microscopic examination.

Physicians usually avoid performing needle biopsies of suspected kidney tumors because of the risk for bleeding or other complications. Some tumors contain a fluid-filled cyst. A small amount of this fluid can be drawn out of the cyst for examination by a pathologist, who will look for and identify the cancer cells. This can help the physician determine an appropriate treatment plan. While no longer common, a similar technique can be used to collect a sample of solid tissue from a noncystic tumor.

Pathology
Broadly speaking, the individual cells that make up RCC tumors fall into four categories based on their appearance under microscopic examination:

• Clear cell
• Granular cell
• Mixed clear and granular
• Sarcomatoid or spindle type

Most studies suggest that the type of cancer cell indicates the relative aggressiveness of the disease.

Under a microscope, clear cell cancers are the least abnormal-looking -- they are round or polygon-shaped and contain an abundance of fat and sugar. The tumors they produce are yellow to orange in color. Clear cell cancers are thought to be the least aggressive (likely to spread) and respond more favorably to treatment.

Few tumors contain only clear cells, however. Darker granular cells usually are present to some degree. These have a larger, darker nucleus and are full of tiny pink granules called mitochondria. The tumors they produce tend to be gray to white in color. Mitochondria are small, oval bodies that provide energy for cell growth. Their presence indicates a more aggressive form of cancer.

Tumors that contain both clear and granular cells are considered mixed. This is the most common form of RCC and indicates the most aggressive form of kidney cancer.

Mixed tumors that contain spindle shaped, sarcomatoid cells have the least favorable prognosis. Although tumors composed exclusively of spindle cells are uncommon, the presence of sarcomatoid cells indicates a form of cancer that grows and spreads quickly.

Treatment

Once a diagnosis of renal cell cancer has been confirmed and the disease's stage determined, doctor and patient decide on a plan for treatment. Factors to consider in this decision include the patient's age and overall health, the extent to which the cancer has spread, and any other physical conditions that might affect the patient's survivability. For example, a patient with one healthy, functioning kidney and one afflicted with an aggressive Stage 2 RCC would be a more likely candidate for radical surgery than a person with only one kidney and a less aggressive Stage 1 cancer.

It is important that the patient and physician make an informed decision together after considering all possible options, side effects, and outcomes. It is imperative that the decision to proceed with a particular treatment be as free from doubt as possible. A confident, positive outlook can help the patient cope with the physical demands surgery and/or therapy will impose on the body and can improve the chances for a speedy recovery.

A second opinion can provide additional information in the decision-making process and help the patient feel that he or she has made the right choice. (Some insurance companies require a second opinion before they approve payment for treatment.)

In general, there are five treatment options for the patient with RCC:

• Surgery -- Removing cancerous tissue in an operation
• Chemotherapy -- Using drugs or chemicals to kill cancer cells
• Radiation therapy -- Using high-energy radiation to kill cancer cells
• Hormone therapy -- Using hormones to prevent cancer cell growth
• Biological or Immunotherapy -- Using compounds produced by the body's disease-fighting system, or laboratory-produced copies of them, to kill cancer cells

Two or more forms of treatment may be used jointly, such as surgery to remove a primary tumor followed by radiation treatment or chemotherapy to kill any cancer cells that may remain in the body.

A sixth form of treatment, gene therapy, is now being explored by researchers who think inherited genetic mutations may cause many cases of RCC. Eventually, a process that uses normal genes to overcome or reverse the cancer-causing process may be developed. Currently, however, gene therapy is not a treatment option.

Surgery
Surgery usually is required to treat RCC. Without it, most patients' chances for survival are poor. Several surgical options are available to the patient and physician; which is most appropriate depends on the patient's condition and the cancer's stage.

Radical Nephrectomy
The most common form of surgery for RCC, radical nephrectomy involves removal of the entire kidney, often along with the attached adrenal gland, surrounding fatty tissues and nearby lymph nodes (regional lymphadenectomy), depending upon how far the cancer has spread.

Partial Nephrectomy
It may be possible to remove only the cancerous tissue and part of the kidney if the tumor is small and confined to the very top or bottom of the kidney. A partial nephrectomy may be the procedure of choice for patients with RCC in both kidneys and for those who have only one functioning kidney.

Arterial Embolization
This procedure usually is reserved for patients whose health does not permit surgery, such as those with heart or lung disease. In arterial embolization, a catheter (very small tube) is inserted through a blood vessel in the groin and passed up to the kidney. A small piece of gelatin sponge is then injected into the artery that supplies blood to the cancerous kidney. This cuts off the flow of blood to the kidney and the cancerous tumor, and both die. The kidney usually is surgically removed at a later date, if and when the patient's health permits.

Surgical Risks
Any form of invasive surgery carries certain risks. Patients contemplating kidney surgery should be advised of the possibility of experiencing complications, such as the following:

• Damage to blood vessels (aorta or vena cava)
• Damage to organs (spleen, pancreas, large or small bowel)
• Failure of the remaining kidney
• Hemorrhage (bleeding) during surgery (intraoperative) or after surgery (postoperative)
• Incisional hernia (bulging of the internal organs beneath the surgical incision, caused by imperfect healing or damage to the overlying muscles)
• Infection
• Pneumothorax (unwanted air in the chest cavity)

Postoperative Prognosis
The natural course of renal cell cancer is more unpredictable than that of most tumors. It is the second most common tumor to undergo spontaneous regression following removal of the primary lesion; this occurs about 0.5% of the time. Another unusual characteristic of RCC is the variability in the growth of the primary tumor.

Once distant disease occurs, survival depends on the extent of the spread and the interval between appearance of metastases and the removal of the kidney.

Overall, the 5-year survival rate for RCC -- all stages combined -- is about 40-45%.

Follow-up Care and Recurrent Kidney Cancer
Some patients who undergo surgery to remove a cancerous kidney or kidney tumors experience a recurrence of the disease. For this reason, patients usually undergo a regimen of follow-up examinations after surgery, typically at 3-month intervals for the first year. These examinations include a complete physical examination, a chest x-ray, complete blood tests, and assessments of liver and kidney function.

If the disease recurs but remains confined to a few small areas, additional surgery may be recommended. Radiation, biological, or chemotherapy also may be tried as an adjuvant or palliative (relief-giving) treatment.

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