Kidney Cancer

Overview
What is Renal Cell Carcinoma (RCC)?
What are some of the primary symptoms of RCC?
How is RCC diagnosed?
What are my treatment options?
Will I need surgery?
What are some of the possible complications of a nephrectomy?
What will be my postoperative prognosis?
What other types of Kidney Cancer exist besides RCC?

Overview
In the United States, kidney cancer accounts for approximately 3% of all adult cancers. According to the American Cancer Society, about 32,000 new cases are diagnosed and about 12,000 people die from the disease annually. Kidney cancer occurs most often in people between the ages of 50 and 70, and affects men almost twice as often as women.

Smokers develop renal cell carcinoma about twice as often as nonsmokers and develop cancer of the renal pelvis about 4 times as often. Not smoking is the most effective way to prevent kidney cancer and it is estimated that the elimination of smoking would reduce the rate of renal pelvis cancer by one-half and the rate of renal cell carcinoma by one-third.

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: erythropoietin (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.

What is Renal Cell Carcinoma (RCC)?
Several types of cancer can develop in the kidneys. Renal cell carcinoma (RCC), the most common form, accounts for approximately 85% of all cases. In RCC, cancerous (malignant) cells develop in the lining of the kidney's tubules and grow into a mass called a tumor. In most cases, a single tumor develops, although more than one tumor can develop within one or both kidneys.

Early diagnosis of kidney cancer is important. As with most types of cancer, the earlier the tumor is 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 spread (metastasized) through the bloodstream or lymphatic system to other parts of the body are more difficult to treat and present an increased risk for mortality.

What are some of the primary symptoms of RCC?
The primary symptoms of RCC include the following:

• Abdominal mass or lump
• Blood in the urine
• Fever
• High blood pressure
• Pain in the side (flank) or lower back not associated with injury
• Persistent fatigue
• Rapid, unexplained weight loss
• Swelling (edema) in the legs and ankles

How is RCC diagnosed?
If the physician suspects RCC, a series of examinations, procedures, and laboratory tests are performed to confirm the diagnosis. A thorough physical examination is performed to assess the patient's health and obtain information about symptoms and a medical history is taken to determine if there are risk factors for RCC.

Imaging Tests
One or more imaging tests are performed to obtain pictures of the kidney(s) and locate abnormalities. Some imaging tests require the injection of a special "tracer" material (dye or low-level radioactive isotope) into the patient's bloodstream.

Computed tomography (CT scan)
CT 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 scan)
An MRI scan 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 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 produced is viewed on a monitor.

Intravenous pyelogram (IVP)
An intravenous pyelogram (IVP) 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 detect tumors or damage caused by a tumor in the kidney.

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

Chest x-ray
A standard chest x-ray may be used to detect RCC that has has spread (metastasized) to the lungs or bones in the chest.

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 the urine (hematuria). Often this blood is present in small amounts or diffused in the urine so that it cannot be seen with the naked eye (called microscopic hematuria). To detect hematuria, a chemical test of the urine is performed. 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

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 cancerous (malignant) 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
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. 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 likely to spread (aggressive) and usually 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.

What are my treatment options?
Once a diagnosis of renal cell cancer has been confirmed and the disease's stage determined, physician and patient decide on a treatment plan. Factors that are considered include the patient's age and overall health and the extent to which the cancer has spread. For example, a patient with one healthy, functioning kidney and one afflicted with an aggressive Stage 2 RCC is a more likely candidate for radical surgery than a patient 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. A confident, positive outlook can help the patient cope with the physical demands of surgery and/or therapy and can improve the chances for recovery.

Treatment options include the following:

• Surgery (to remove cancerous tissue)
• Chemotherapy (using drugs to destroy cancer cells)
• Radiation therapy (using high-energy radiation to destroy cancer cells and shrink tumors)
• Hormone therapy (using hormones to prevent cancer cell growth)
• Biological or Immunotherapy (using compounds produced by the body's immune system, or laboratory-produced copies of them, to destroy cancer cells)

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

Will I need surgery?
Surgery is the standard treatment for RCC. There are several surgical options, depending on the stage of the disease and the overall health of the patient.

Prior to surgery, most patients undergo an electrocardiogram (ECG), chest x-ray, complete blood count (CBC), and electrolyte profile with BUN and creatinine. Imaging tests (e.g., CT scan, intravenous pyelogram [IVP], MRI scan) are performed to determine the exact location of the kidneys and to detect anatomic variations (e.g., duplicated ureter, horseshoe kidneys), kidney stones, and cancer of the bladder, ureter, or other kidney.

When the tumor is small and confined to the top or bottom portion of the kidney, a partial nephrectomy (removal of part of the kidney) may be performed. This procedure also may be used to treat patients with RCC in both kidneys and patients who have only one functioning kidney.

Radical nephrectomy is the most common treatment for RCC. This procedure, which is performed under general anesthesia, involves removal of the entire kidney and the adrenal gland. It also may include removal of surrounding tissue and nearby lymph nodes (regional lymphadenectomy), depending on how far the cancer has spread.

Radical nephrectomy may be performed through a large abdominal incision (open radical nephrectomy) or 4 or 5 smaller incisions (laparoscopic radical nephrectomy). In laparoscopic radical nephrectomy, an instrument consisting of a light and camera lens that produces magnified images (called a laparoscope) is used to allow the physician to see inside the abdomen.
Tiny instruments are inserted through the incisions and used to separate the kidney from surrounding structures (e.g., ureter, blood vessels). The physician then enlarges one of the incisions and removes the kidney. Laparoscopic radical nephrectomy takes slightly longer to perform than open surgery.

Generally, the risk for complications and blood loss during surgery is similar in both procedures. Patients who undergo laparoscopic nephrectomy may require less pain medication, usually are discharged from the hospital sooner, and often are able to resume normal activities earlier.

Arterial embolization may be used in patients who are unable to undergo surgery (e.g., patients with severe heart disease). In this procedure, a catheter (thin tube) is introduced into the artery in the groin that supplies blood to the cancerous kidney. A small piece of material (e.g., gelatin sponge) is then inserted into the catheter to cut off the blood supply, destroying the tumor and the organ. If the patient is able to undergo surgery at a later date, the kidney is removed.

What are some of the possible complications of a nephrectomy?
Complications of nephrectomy include the following:

• Damage to surround organs (e.g., spleen, pancreas, large or small intestine) and blood vessels (e.g., aorta, vena cava)
• Failure of the remaining kidney
• Hemorrhage (excessive bleeding) during or after surgery
• Incisional hernia (protrusion of organs or tissue through the abdominal wall)
• Infection
• Pneumothorax (air in the chest cavity, outside the lungs)

What will be my Postoperative Prognosis?
Renal cell cancer is the second most common tumor type to undergo spontaneous regression following removal of the primary lesion; this occurs in about 0.5% of cases. Once metastasis occurs, prognosis depends on the extent of the spread and the interval between kidney removal and the appearance of metastases. Overall, the 5-year survival rate for RCC—all stages combined—is about 40-45%.

Patients who undergo kidney cancer surgery may experience a recurrence of the disease. For this reason, most patients 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, chest x-ray, complete blood tests, and assessments of liver and kidney function.

If the disease recurs and remains confined to a few small areas, additional surgery may be recommended. Radiation therapy, biological therapy (immunotherapy), or chemotherapy may be used in addition to surgery (called adjuvant treatment) or to relieve symptoms (called palliative treatment).

What other types of Kidney Cancer exist besides RCC?
Transitional Cell Carcinoma
About 6% to 7% of kidney cancers begin not in the kidney itself, but in the renal pelvis, the point where the kidney joins the tube that carries urine form the kidney to the bladder (ureter). These tumors are called transitional cell carcinomas and are made up of cancer cells different from those that characterize RCC. Research indicates these tumors are caused by cigarette smoking.

The symptoms of transitional cell carcinoma are quite similar to those of RCC, and include hematuria and back or flank pain.

If found early, these cancers have a 90% cure rate. Treatment usually involves surgical removal of the kidney, ureter, and portion of the bladder connecting to the ureter. Depending on the stage of the cancer, chemotherapy and radiation may be used as adjuvant treatments.

The prognosis for cure declines sharply when the cancer invades the ureter wall or penetrates the kidney. Regular follow-up examinations after surgery are important, as transitional cell carcinoma is prone to recurrence.

Wilms' Tumor
A relatively rare form of kidney cancer, Wilms' tumor (also known as nephroblastoma) accounts for about 5% to 8% of kidney tumors in children. It occurs in about 7 out of every 1 million children around the world per year, regardless of race, and is thought to be caused by genetic mutation that causes abnormal growth within the tubules of the kidney nephrons. The disease occurs equally in boys and girls. It typically first appears in children between 2 and 5 years of age but has been known to occur rarely in adolescents as old as 15.

Wilms' tumor can arise anywhere within the kidney's tissues. Untreated, it can spread to the veins, lymph nodes, adrenal glands, large or small bowel, and liver. Fortunately, advances in radiation and chemotherapy over the past few decades, pediatric anesthesia, and surgery have made Wilms' tumor one of the most curable of all childhood cancers. Today the 5-year survival rate approaches 90%.

Renal Sarcoma
Renal sarcoma is a rare disease of the kidney's connective tissues that accounts for less than 1% of all kidney tumors. Its symptoms are similar to those of RCC: hematuria, pain in the back or flank, or a lump and mass in the abdomen. In most cases, it is impossible to differentiate renal sarcoma from RCC externally, so the diagnosis usually is made after examination of a CT scan or MRI procedure.

Such tumors will grow and spread to adjacent organs, bones, and lymph nodes if left untreated. The only potentially curative form of treatment is surgery, usually radical or partial nephrectomy, sometimes with radiation or chemotherapy.