Renal Cell Cancer

  • Dana-Farber/Brigham and Women's Cancer Care

    Renal cell cancer is the most common type of kidney cancer. It begins in the lining of the renal tubules, which filter the blood and produce urine. Learn about renal cell cancer and find information on how we support and care for people with renal cell cancer before, during, and after treatment.

Treatment 

Dana-Farber’s Lank Center for Genitourinary Oncology provides compassionate care informed by research into the most effective therapies for prostate, kidney, and testicular cancer, as well as many other rare and common cancers.

Staffed by medical, urologic, and radiation oncologists, our center offers the latest treatments fueled by ongoing discovery. Our genitourinary cancer experts work together to create an individualized treatment plan that offers each patient the most effective care.

During your first appointment at the center, you’ll meet with three specialists: a medical oncologist, a radiation oncologist, and urologist. Working with you, they will evaluate, discuss, and recommend specific treatments to create a care plan that takes your individual needs into account.

In addition to offering the latest in clinical care, we provide a wide range of resources — from support groups to nutritional advice to complementary therapies — to support you physically and emotionally throughout your treatment.

Our clinicians are experts in treating all types of genitourinary cancer, including: 

  • Adrenal cancer
  • Adrenocortical carcinoma
  • Bladder cancer
  • Embroynal cancer
  • Germ cell testicular cancer
  • Kidney tumor
  • Penile cancer
  • Prostate cancer
  • Renal cell cancer, transitional cell
  • Renal cell cancer
  • Rhabdoid tumor of the kidney 
  • Seminoma
  • Testicular cancer
  • Testicular choriocarcinoma
  • Testicular cancer (non-seminoma)
  • Urethral cancer
  • Urachal cancer
  • Ureteral cancer
  • Urothelial cancer
  • Wilms kidney tumor

Learn more about our genitourinary cancer treatment center 

Contact us 

New patients 

If you have never been seen before at Dana-Farber/Brigham and Women's Cancer Center, please call 877-442-3324 or use this online form to make an appointment.

For other patient questions or information, call us at 617-632-3466.

Fax: 617-632-2557

Referring physicians: 617-632-2682

Mailing address
Dana-Farber Cancer Institute
Attn: Lank Center for Genitourinary Oncology
450 Brookline Ave.
Boston, MA 02115-5450

Information for: Patients | Healthcare Professionals

General Information About Renal Cell Cancer

Renal cell cancer is a disease in which malignant (cancer) cells form in tubules of the kidney.

Renal cell cancer (also called kidneycancer or renal adenocarcinoma) is a disease in which malignant (cancer) cells are found in the lining of tubules (very small tubes) in the kidney. There are 2 kidneys, one on each side of the backbone, above the waist. The tiny tubules in the kidneys filter and clean the blood, taking out waste products and making urine. The urine passes from each kidney into the bladder through a long tube called a ureter. The bladder stores the urine until it is passed from the body.


Anatomy of the male urinary system; shows the right and left kidneys, the ureters, the bladder filled with urine, and the urethra passing through the penis. The inside of the left kidney shows the renal pelvis. An inset shows the renal tubules and urine.  Also shown is the prostate.

Anatomy of the female urinary system; shows the right and left kidneys, the ureters, the bladder filled with urine, and the urethra. The inside of the left kidney shows the renal pelvis. An inset shows the renal tubules and urine. The uterus is also shown.

Anatomy of the male urinary system (left) and female urinary system (right) showing the kidneys, ureters, bladder, and urethra. Urine is made in the renal tubules and collects in the renal pelvis of each kidney. The urine flows from the kidneys through the ureters to the bladder. The urine is stored in the bladder until it leaves the body through the urethra.

Cancer that starts in the ureters or the renal pelvis (the part of the kidney that collects urine and drains it to the ureters) is different from renal cell cancer. (See the PDQ summary about Transitional Cell Cancer of the Renal Pelvis and Ureter Treatment for more information).

Smoking and misuse of certain pain medicines can affect the risk of renal cell cancer.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn't mean that you will not get cancer. Talk with your doctor if you think you may be at risk. Risk factors for renal cell cancer include the following:

  • Smoking.
  • Misusing certain pain medicines, including over-the-counter pain medicines, for a long time.
  • Having certain geneticconditions, such as von Hippel-Lindau disease or hereditary papillary renal cell carcinoma.

Possible signs of renal cell cancer include blood in the urine and a lump in the abdomen.

These and other symptoms may be caused by renal cell cancer. Other conditions may cause the same symptoms. There may be no symptoms in the early stages. Symptoms may appear as the tumor grows. Check with your doctor if you have any of the following problems:

  • Blood in the urine.
  • A lump in the abdomen.
  • A pain in the side that doesn't go away.
  • Loss of appetite.
  • Weight loss for no known reason.
  • Anemia.

Tests that examine the abdomen and kidneys are used to detect (find) and diagnose renal cell cancer.

The following tests and procedures may be used:

  • Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
  • Ultrasound exam: A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram.
  • Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it.
  • Urinalysis: A test to check the color of urine and its contents, such as sugar, protein, red blood cells, and white blood cells.
  • Liver function test: A procedure in which a sample of blood is checked to measure the amounts of enzymes released into it by the liver. An abnormal amount of an enzyme can be a sign that cancer has spread to the liver. Certain conditions that are not cancer may also increase liver enzyme levels.
  • Intravenous pyelogram (IVP): A series of x-rays of the kidneys, ureters, and bladder to find out if cancer is present in these organs. A contrast dye is injected into a vein. As the contrast dye moves through the kidneys, ureters, and bladder, x-rays are taken to see if there are any blockages.
  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
  • MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
  • Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer. To do a biopsy for renal cell cancer, a thin needle is inserted into the tumor and a sample of tissue is withdrawn.

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) and treatment options depend on the following:

  • The stage of the disease.
  • The patient's age and general health.

Stages of Renal Cell Cancer

After renal cell cancer has been diagnosed, tests are done to find out if cancer cells have spread within the kidney or to other parts of the body.

The process used to find out if cancer has spread within the kidney or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. The following tests and procedures may be used in the staging process:

  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
  • MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
  • Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.

There are three ways that cancer spreads in the body.

Cancer can spread through tissue, the lymph system, and the blood:

  • Tissue. The cancer spreads from where it began by growing into nearby areas.
  • Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
  • Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.

Cancer may spread from where it began to other parts of the body.

When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.

  • Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor (metastatic tumor) in another part of the body.
  • Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor (metastatic tumor) in another part of the body.

The metastatic tumor is the same type of cancer as the primary tumor. For example, if renal cell cancer spreads to the bone, the cancer cells in the bone are actually cancerous renal cells. The disease is metastatic renal cell cancer, not bone cancer.

The following stages are used for renal cell cancer:

Tumor size compared to everyday objects; shows various measurements of a tumor compared to a pea, peanut, walnut, and lime
Pea, peanut, walnut, and lime show tumor sizes.

Stage I

In stage I, the tumor is 7 centimeters or smaller and is found only in the kidney.

Stage II

In stage II, the tumor is larger than 7 centimeters and is found only in the kidney.

Stage III

In stage III:

  • the tumor is any size and cancer is found only in the kidney and in 1 or more nearby lymph nodes; or
  • cancer is found in the main blood vessels of the kidney or in the layer of fatty tissue around the kidney. Cancer may be found in 1 or more nearby lymph nodes.

Stage IV

In stage IV, cancer has spread:

  • beyond the layer of fatty tissue around the kidney and may be found in the adrenal gland above the kidney with cancer, or in nearby lymph nodes; or
  • to other organs, such as the lungs, liver, bones, or brain, and may have spread to lymph nodes.

Recurrent Renal Cell Cancer

Recurrentrenal cell cancer is cancer that has recurred (come back) after it has been treated. The cancer may come back many years after initial treatment, in the kidney or in other parts of the body.

Treatment Option Overview

There are different types of treatment for patients with renal cell cancer.

Different types of treatments are available for patients with renal cell cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Five types of standard treatment are used:

Surgery

Surgery to remove part or all of the kidney is often used to treat renal cell cancer. The following types of surgery may be used:

  • Partial nephrectomy: A surgical procedure to remove the cancer within the kidney and some of the tissue around it. A partial nephrectomy may be done to prevent loss of kidney function when the other kidney is damaged or has already been removed.
  • Simple nephrectomy: A surgical procedure to remove the kidney only.
  • Radical nephrectomy: A surgical procedure to remove the kidney, the adrenal gland, surrounding tissue, and, usually, nearby lymph nodes.

A person can live with part of 1 working kidney, but if both kidneys are removed or not working, the person will need dialysis (a procedure to clean the blood using a machine outside of the body) or a kidney transplant (replacement with a healthy donated kidney). A kidney transplant may be done when the disease is in the kidney only and a donated kidney can be found. If the patient has to wait for a donated kidney, other treatment is given as needed.

When surgery to remove the cancer is not possible, a treatment called arterial embolization may be used to shrink the tumor. A small incision is made and a catheter (thin tube) is inserted into the main blood vessel that flows to the kidney. Small pieces of a special gelatin sponge are injected through the catheter into the blood vessel. The sponges block the blood flow to the kidney and prevent the cancer cells from getting oxygen and other substances they need to grow.

Even if the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given chemotherapy or radiation therapy after surgery to kill any cancer cells that are left. Treatment given after the surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.

See Drugs Approved for Kidney (Renal Cell) Cancer for more information.

Biologic therapy

Biologic therapy is a treatment that uses the patient's immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body's natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.

See Drugs Approved for Kidney (Renal Cell) Cancer for more information.

Targeted therapy

Targeted therapy uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Targeted therapy with antiangiogenic agents are used to treat advanced renal cell cancer. Antiangiogenic agents keep blood vessels from forming in a tumor, causing the tumor to starve and stop growing or to shrink. Monoclonal antibodies and kinase inhibitors are two types of antiangiogenic agents used to treat renal cell cancer.

Monoclonal antibody therapy uses antibodies made in the laboratory, from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells. Monoclonal antibodies used to treat renal cell cancer attach to and block substances that cause new blood vessels to form in tumors.

Kinase inhibitors stop cells from dividing and may prevent the growth of new blood vessels that tumors need to grow.

See Drugs Approved for Kidney (Renal Cell) Cancer for more information.

New types of treatment are being tested in clinical trials.

Information about clinical trials is available from the NCI Web site.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment Options for Renal Cell Cancer

Stage I Renal Cell Cancer

Treatment of stage I renal cell cancer may include the following:

  • Surgery (radical nephrectomy, simple nephrectomy, or partial nephrectomy).
  • Radiation therapy as palliative therapy to relieve symptoms in patients who cannot have surgery.
  • Arterial embolization as palliative therapy.
  • A clinical trial of a new treatment.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I renal cell cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage II Renal Cell Cancer

Treatment of stage II renal cell cancer may include the following:

  • Surgery (radical nephrectomy or partial nephrectomy).
  • Surgery (nephrectomy), before or after radiation therapy.
  • Radiation therapy as palliative therapy to relieve symptoms in patients who cannot have surgery.
  • Arterial embolization as palliative therapy.
  • A clinical trial of a new treatment.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II renal cell cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage III Renal Cell Cancer

Treatment of stage III renal cell cancer may include the following:

  • Surgery (radical nephrectomy). Blood vessels of the kidney and some lymph nodes may also be removed.
  • Arterial embolization followed by surgery (radical nephrectomy).
  • Radiation therapy as palliative therapy to relieve symptoms and improve the quality of life.
  • Arterial embolization as palliative therapy.
  • Surgery (nephrectomy) as palliative therapy.
  • Radiation therapy before or after surgery (radical nephrectomy).
  • A clinical trial of biologic therapy following surgery.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III renal cell cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage IV and Recurrent Renal Cell Cancer

Treatment of stage IV and recurrentrenal cell cancer may include the following:

  • Surgery (radical nephrectomy).
  • Surgery (nephrectomy) to reduce the size of the tumor.
  • Targeted therapy.
  • Biologic therapy.
  • Radiation therapy as palliative therapy to relieve symptoms and improve the quality of life.
  • A clinical trial of a new treatment.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV renal cell cancer and recurrent renal cell cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

To Learn More About Renal Cell Cancer

For more information from the National Cancer Institute about renal cell cancer, see the following:

For general cancer information and other resources from the National Cancer Institute, see the following:


This information is provided by the National Cancer Institute.

This information was last updated on November 14, 2013.


General Information About Renal Cell Cancer

Incidence and Mortality

Estimated new cases and deaths from renal cell (kidney and renal pelvis) cancer in the United States in 2014:[1]

  • New cases: 63,920.
  • Deaths: 13,860.

Follow-up and Survivorship

Renal cell cancer, also called renal adenocarcinoma, or hypernephroma, can often be cured if it is diagnosed and treated when still localized to the kidney and to the immediately surrounding tissue. The probability of cure is directly related to the stage or degree of tumor dissemination. Even when regional lymphatics or blood vessels are involved with tumor, a significant number of patients can achieve prolonged survival and probable cure.[2] When distant metastases are present, disease-free survival is poor; however, occasional selected patients will survive after surgical resection of all known tumor. Because a majority of patients are diagnosed when the tumor is still relatively localized and amenable to surgical removal, approximately 40% of all patients with renal cell cancer survive for 5 years. Occasionally, patients with locally advanced or metastatic disease may exhibit indolent courses lasting several years. Late tumor recurrence many years after initial treatment also occasionally occurs.

Renal cell cancer is one of the few tumors in which well-documented cases of spontaneous tumor regression in the absence of therapy exist, but this occurs very rarely and may not lead to long-term survival.

Treatment modalities

Surgical resection is the mainstay of treatment of this disease. Even in patients with disseminated tumor, locoregional forms of therapy may play an important role in palliating symptoms of the primary tumor or of ectopic hormone production. Systemic therapy has demonstrated only limited effectiveness.

Related Summaries

Other PDQ summaries containing information related to renal cell cancer include the following:

  • Transitional Cell Cancer of the Renal Pelvis and Ureter Treatment
  • Wilms Tumor Treatment

References:

  1. American Cancer Society.: Cancer Facts and Figures 2014. Atlanta, Ga: American Cancer Society, 2014. Available online. Last accessed February 14, 2014.

  2. Sene AP, Hunt L, McMahon RF, et al.: Renal carcinoma in patients undergoing nephrectomy: analysis of survival and prognostic factors. Br J Urol 70 (2): 125-34, 1992.

Cellular Classification of Renal Cell Cancer

Approximately 85% of renal cell cancers are adenocarcinomas, and most of those are of proximal tubular origin. Most of the remainder are transitional cell carcinomas of the renal pelvis. (Refer to the PDQ summary on Transitional Cell Cancer of the Renal Pelvis and Ureter Treatment for more information.) Adenocarcinomas may be separated into clear cell and granular cell carcinomas; however, the two cell types may occur together in some tumors. Some investigators have found that granular cell tumors have a worse prognosis, but this finding is not universal. Distinguishing between well-differentiated renal adenocarcinomas and renal adenomas can be difficult. The diagnosis is usually made arbitrarily on the basis of size of the mass, but size alone should not influence the treatment approach, since metastases can occur with lesions as small as 0.5 centimeter.

Stage Information for Renal Cell Cancer

The staging system for renal cell cancer is based on the degree of tumor spread beyond the kidney.[1][2][3] Involvement of blood vessels may not be a poor prognostic sign if the tumor is otherwise confined to the substance of the kidney. Abnormal liver function test results may be caused by a paraneoplastic syndrome that is reversible with tumor removal, and these types of results do not necessarily represent metastatic disease. Except when computed tomography (CT) examination is equivocal or when iodinated contrast material is contraindicated, CT scanning is as good as or better than magnetic resonance imaging for detecting renal masses.[4]

Definitions of TNM

The American Joint Committee on Cancer has designated staging by TNM classification to define renal cell cancer.[5]

Table 1. Primary Tumor (T)a

TX

Primary tumor cannot be assessed.

T0

No evidence of primary tumor.

T1

Tumor ≤7 cm in greatest dimension, limited to the kidney.

T1a

Tumor ≤4 cm in greatest dimension, limited to the kidney.

T1b

Tumor >4 cm but not >7 cm in greatest dimension, limited to the kidney.

T2

Tumor >7 cm in greatest dimension, limited to the kidney.

T2a

Tumor >7 cm but ≤10 cm in greatest dimension, limited to the kidney.

T2b

Tumor >10 cm, limited to the kidney.

T3

Tumor extends into major veins or perinephric tissues but not into the ipsilateral adrenal gland and not beyond Gerota fascia.

T3a

Tumor grossly extends into the renal vein or its segmental (muscle containing) branches, or tumor invades perirenal and/or renal sinus fat but not beyond Gerota fascia.

T3b

Tumor grossly extends into the vena cava below the diaphragm.

T3c

Tumor grossly extends into the vena cava above the diaphragm or invades the wall of the vena cava.

T4

Tumor invades beyond Gerota fascia (including contiguous extension into the ipsilateral adrenal gland).

aReprinted with permission from AJCC: Kidney. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 479-89.

Table 2. Regional Lymph Nodes (N)a

NX

Regional lymph nodes cannot be assessed.

N0

No regional lymph node metastasis.

N1

Metastases in regional lymph node(s).

aReprinted with permission from AJCC: Kidney. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 479-89.

Table 3. Distant Metastasis (M)a

M0

No distant metastasis.

M1

Distant metastasis.

aReprinted with permission from AJCC: Kidney. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 479-89.

Table 4. Anatomic Stage/Prognostic Groupsa

Stage

T

N

M

I

T1

N0

M0

II

T2

N0

M0

III

T1 or T2

N1

M0

T3

N0 or N1

M0

IV

T4

Any N

M0

Any T

Any N

M1

aReprinted with permission from AJCC: Kidney. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 479-89.

References:

  1. Bassil B, Dosoretz DE, Prout GR Jr: Validation of the tumor, nodes and metastasis classification of renal cell carcinoma. J Urol 134 (3): 450-4, 1985.

  2. Golimbu M, Joshi P, Sperber A, et al.: Renal cell carcinoma: survival and prognostic factors. Urology 27 (4): 291-301, 1986.

  3. Robson CJ, Churchill BM, Anderson W: The results of radical nephrectomy for renal cell carcinoma. J Urol 101 (3): 297-301, 1969.

  4. Consensus conference. Magnetic resonance imaging. JAMA 259 (14): 2132-8, 1988.

  5. Kidney. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 479-89.

Treatment Option Overview

Current treatment cures more than 50% of patients with stage I disease, but results in patients with stage IV disease are very poor. Thus, all patients with newly diagnosed renal cell cancer can appropriately be considered candidates for clinical trials, when possible.

Stage I Renal Cell Cancer

Stage I renal cell cancer is defined by the American Joint Committee on Cancer's TNM classification system:

  • T1, N0, M0

Surgical resection is the accepted, often curative, therapy for stage I renal cell cancer. Resection may be simple or radical. The latter operation includes removal of the kidney, adrenal gland, perirenal fat, and Gerota fascia, with or without a regional lymph node dissection. Some, but not all, surgeons believe the radical operation yields superior results. In patients who are not candidates for surgery, external-beam radiation therapy (EBRT) or arterial embolization can provide palliation. In patients with bilateral stage I neoplasms (concurrent or subsequent), bilateral partial nephrectomy or unilateral partial nephrectomy with contralateral radical nephrectomy, when technically feasible, may be a preferred alternative to bilateral nephrectomy with dialysis or transplantation.[2] Increasing evidence suggests that a partial nephrectomy is curative in selected cases. A pathologist should examine the gross specimen as well as the frozen section from the parenchymal margin of excision.[3]

Standard treatment options:

  1. Radical nephrectomy.[4]
  2. Simple nephrectomy.[4]
  3. Partial nephrectomy (selected patients).[2][4]
  4. EBRT (palliative).[4]
  5. Arterial embolization (palliative).[4][5]
  6. Clinical trials.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I renal cell cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Kidney. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 479-89.

  2. Novick AC, Streem S, Montie JE, et al.: Conservative surgery for renal cell carcinoma: a single-center experience with 100 patients. J Urol 141 (4): 835-9, 1989.

  3. Thrasher JB, Robertson JE, Paulson DF: Expanding indications for conservative renal surgery in renal cell carcinoma. Urology 43 (2): 160-8, 1994.

  4. deKernion JB, Berry D: The diagnosis and treatment of renal cell carcinoma. Cancer 45 (7 Suppl): 1947-56, 1980.

  5. Swanson DA, Wallace S, Johnson DE: The role of embolization and nephrectomy in the treatment of metastatic renal carcinoma. Urol Clin North Am 7 (3): 719-30, 1980.

Stage II Renal Cell Cancer

Stage II renal cell cancer is defined by the American Joint Committee on Cancer's TNM classification system:

  • T2, N0, M0

Radical resection is the accepted, often curative, therapy for stage II renal cell cancer. The operation includes removal of the kidney, adrenal gland, perirenal fat, and Gerota fascia, with or without a regional lymph node dissection.[2] Lymphadenectomy is commonly employed, but its effectiveness has not been definitively proven. External-beam radiation therapy (EBRT) has been given before or after nephrectomy without conclusive evidence that this improves survival when compared with the results of surgery alone; however, it may be of benefit in selected patients with more extensive tumors. In patients who are not candidates for surgery, arterial embolization can provide palliation.

Standard treatment options:

  1. Radical nephrectomy.[3]
  2. Nephrectomy before or after EBRT (selected patients).[3]
  3. Partial nephrectomy (selected patients).[3]
  4. EBRT (palliative).[3]
  5. Arterial embolization (palliative).
  6. Clinical trials.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II renal cell cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Kidney. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 479-89.

  2. Phillips E, Messing EM: Role of lymphadenectomy in the treatment of renal cell carcinoma. Urology 41 (1): 9-15, 1993.

  3. deKernion JB, Berry D: The diagnosis and treatment of renal cell carcinoma. Cancer 45 (7 Suppl): 1947-56, 1980.

Stage III Renal Cell Cancer

Stage III renal cell cancer is defined by the American Joint Committee on Cancer's TNM classification system:

  • T1 or T2, N1, M0
  • T3, N0 or N1, M0

Treatment information for patients whose disease has the following classification:

  • T3a, N0, M0

Radical resection is the accepted, often curative, therapy for stage III renal cell cancer. The operation includes removal of the kidney, adrenal gland, perirenal fat, and Gerota fascia, with or without a regional lymph node dissection.[2] Lymphadenectomy is commonly employed, but its effectiveness has not been definitively proven. External-beam radiation therapy (EBRT) has been given before or after nephrectomy without conclusive evidence that this improves survival when compared with the results of surgery alone; however, it may be of benefit in selected patients with more extensive tumors. In patients who are not candidates for surgery, arterial embolization can provide palliation. In patients with bilateral stage T3a neoplasms (concurrent or subsequent), bilateral partial nephrectomy or unilateral partial nephrectomy with contralateral radical nephrectomy, when technically feasible, may be a preferred alternative to bilateral nephrectomy with dialysis or transplantation.[3]

Treatment information for patients whose disease has the following classification:

  • T3b, N0, M0

Radical resection is the accepted, often curative, therapy for this stage of renal cell cancer. The operation includes removal of the kidney, adrenal gland, perirenal fat, and Gerota fascia, with or without a regional lymph node dissection. Lymphadenectomy is commonly employed, but its effectiveness has not been definitively proven. Surgery is extended to remove the entire renal vein and caval thrombus and a portion of the vena cava as necessary.[4] EBRT has been given before or after nephrectomy without conclusive evidence that this improves survival when compared with the results of surgery alone; however, it may be of benefit in selected patients with more extensive tumors. In patients who are not candidates for surgery, arterial embolization can provide palliation. In patients with stage T3b neoplasms who manifest concurrent or subsequent renal cell carcinoma in the contralateral kidney, a partial nephrectomy, when technically feasible, may be a preferred alternative to bilateral nephrectomy with dialysis or transplantation.[3][5][6]

Treatment information for patients whose disease has the following classifications:

  • T1, N1, M0
  • T2, N1, M0
  • T3, N1, M0
  • T3a, N1, M0
  • T3b, N1, M0
  • T3c, N1, M0

This stage of renal cell cancer is curable with surgery in a small minority of cases. A radical nephrectomy and lymph node dissection is necessary. The value of preoperative and postoperative EBRT has not been demonstrated, but EBRT may be used for palliation in patients who are not candidates for surgery. Arterial embolization of the tumor with gelfoam or other materials may be employed preoperatively to reduce blood loss at nephrectomy or for palliation in patients with inoperable disease.

Standard treatment options:

  1. Radical nephrectomy with renal vein and, as necessary, vena caval resection (for T3b tumors).[4] Radical nephrectomy with lymph node dissection.
  2. Preoperative embolization and radical nephrectomy.[7][8]
  3. EBRT (palliative).[7]
  4. Tumor embolization (palliative).[8]
  5. Palliative nephrectomy.
  6. Preoperative or postoperative EBRT and radical nephrectomy.[7]
  7. Clinical trials involving adjuvant interferon-alpha.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III renal cell cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Kidney. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 479-89.

  2. Phillips E, Messing EM: Role of lymphadenectomy in the treatment of renal cell carcinoma. Urology 41 (1): 9-15, 1993.

  3. Novick AC, Streem S, Montie JE, et al.: Conservative surgery for renal cell carcinoma: a single-center experience with 100 patients. J Urol 141 (4): 835-9, 1989.

  4. Hatcher PA, Anderson EE, Paulson DF, et al.: Surgical management and prognosis of renal cell carcinoma invading the vena cava. J Urol 145 (1): 20-3; discussion 23-4, 1991.

  5. deKernion JB: Management of renal adenocarcinoma. In: deKernion JB, Paulson DF, eds.: Genitourinary Cancer Management. Philadelphia, Pa: Lea and Febiger, 1987, pp 187-217.

  6. Angermeier KW, Novick AC, Streem SB, et al.: Nephron-sparing surgery for renal cell carcinoma with venous involvement. J Urol 144 (6): 1352-5, 1990.

  7. deKernion JB, Berry D: The diagnosis and treatment of renal cell carcinoma. Cancer 45 (7 Suppl): 1947-56, 1980.

  8. Swanson DA, Wallace S, Johnson DE: The role of embolization and nephrectomy in the treatment of metastatic renal carcinoma. Urol Clin North Am 7 (3): 719-30, 1980.

Stage IV and Recurrent Renal Cell Cancer

Stage IV renal cell cancer is defined by the American Joint Committee on Cancer's TNM classification system:

  • T4, any N, M0
  • Any T, any N, M1

The prognosis for any treated renal cell cancer patient with progressing, recurring, or relapsing disease is poor, regardless of cell type or stage. Almost all patients with stage IV renal cell cancer are incurable. The question and selection of further treatment depends on many factors, including prior treatment and site of recurrence, as well as individual patient considerations. Carefully selected patients may benefit from surgical resection of localized metastatic disease, particularly if they have had a prolonged, disease-free interval since their primary therapy.

Local Therapy

Tumor embolization, external-beam radiation therapy (EBRT), and nephrectomy can aid in the palliation of symptoms caused by the primary tumor or related ectopic hormone or cytokine production. For patients with metastatic disease, two randomized studies have demonstrated an overall survival (OS) benefit in selected patients who have undergone initial cytoreductive nephrectomy prior to the administration of interferon-alpha.[2][3]

In the larger study, 246 patients were randomly assigned to either undergo a nephrectomy followed by interferon-alpha or receive interferon-alpha alone.[2] The median OS was 11.1 months when the primary tumor was removed first (95% confidence interval [CI], 9.2–16.5) compared with 8.1 months in the control arm (95% CI, 5.4–9.5; P = .05). In the smaller study, 85 patients with identical eligibility criteria were randomly assigned to treatment as in the larger study.[3] Patients who underwent nephrectomy prior to receiving interferon-alpha had a median OS of 17 months compared with an OS of 7 months in patients who received interferon-alpha alone (hazard ratio [HR], 0.54; 95% CI, 0.31–0.94; P = .03).

These studies were restricted to patients who were asymptomatic or minimally symptomatic, with a performance status (PS) of zero or one, according to the Eastern Cooperative Oncology Group (ECOG) rating scale; these patients were also considered to be candidates for postoperative immunotherapy.[2][3][Level of evidence: 1iiA] Whether the benefit of cytoreductive nephrectomy extends to patients who are not subsequently treated with interferon-alpha has not been tested.

Selected patients with solitary or a limited number of distant metastases can achieve prolonged survival with nephrectomy and surgical resection of the metastases.[4][5][6][7][8][9] Even patients with brain metastases had similar results.[10] The likelihood of achieving therapeutic benefit with this approach appears enhanced in patients with a long disease-free interval between the initial nephrectomy and the development of metastatic disease.

Cytokine Therapy

Cytokine therapy with interferon-alpha or interleukin-2 (IL-2) has been shown to induce objective responses, and interferon-alpha appears to have a modest impact on survival in selected patients. Interferon-alpha has approximately a 15% objective response rate in appropriately selected individuals.[11] In general, these patients have nonbulky pulmonary and/or soft tissue metastases with excellent PS ratings of zero or one, according to the ECOG rating scale, and the patients show no weight loss. The interferon-alpha doses used in studies reporting good response rates have been in an intermediate range (6–20 million units 3 times weekly). A Cochrane analysis of six randomized trials, with a total of 963 patients, indicated an HR for survival of 0.78 (CI, 0.67–0.90) or a weighted average improvement in survival of 2.6 months.[11][Level of evidence: 1iiA]

High-dose IL-2 produces a similar overall response rate to interferon-alpha, but approximately 5% of patients had durable complete remissions.[12][13][14][15][16][17] IL-2 has never been shown in a randomized, controlled trial to result in longer survival. High-dose IL-2 is used because it is the only systemic therapy that has been associated with inducing durable complete remissions, albeit in a small fraction (about 5%) of patients who are eligible for this treatment. The optimum dose of IL-2 is unknown. High-dose therapy appears to be associated with higher response rates but with more toxic effects. Low-dose inpatient regimens have activity against renal cell carcinoma with fewer toxic effects, especially hypotension, but have not been shown to be superior to placebo or any alternative regimen with regard to survival or quality of life.[18] Outpatient subcutaneous administration has also demonstrated responses with acceptable toxic effects but, again, with unclear survival or quality of life benefit.[19] Combinations of IL-2 and interferon-alpha have been studied, but outcomes have not been better with high-dose or low-dose IL-2 alone.[20][21]

Antiangiogenic and Other Targeted Therapy

A growing understanding of the biology of cancer in general, and renal cell carcinoma in particular, has led to the development and U.S. Food and Drug Administration (FDA) approval of six new agents targeting specific growth pathways. Two of the approved targeted therapies block the mammalian target of rapamycin (mTOR), a serine/threonine protein kinase that regulates cell growth, division, and survival.

Temsirolimus

Temsirolimus, an intravenously administered mTOR inhibitor, was shown to result in prolonged OS compared with interferon-alpha in a phase III randomized controlled trial that enrolled intermediate- and poor-risk patients. The trial enrolled patients with a variety of subtypes of renal cell carcinoma and was not restricted to clear cell kidney cancer. The HR for death was 0.73 (95% CI, 0.58–0.92, P = .008), making temsirolimus the only therapy for renal cell carcinoma to have clearly been shown to result in longer OS than interferon-alpha using conventional statistical analysis.[22]

Everolimus

Everolimus is an orally administered mTOR inhibitor that was evaluated in a double-blind, randomized, placebo-controlled phase III trial. The trial enrolled patients with metastatic renal cell carcinoma with a clear-cell component that had progressed during or within 6 months of stopping treatment with sunitinib or sorafenib, or both drugs. Median progression-free survival (PFS) was 4.0 months with everolimus compared with 1.9 months with placebo.[23] No difference in OS was reported.

Anti-VEGF

Based on research showing that most clear-cell renal cell carcinomas carried a mutation resulting in constitutive production of cytokines stimulating angiogenesis, several agents that targeted vascular endothelial growth factor (VEGF)-mediated pathways were developed. Several of these agents have been shown in randomized, controlled trials to significantly delay progression of clear-cell renal cell carcinoma, but none has resulted in a statistically significant increase in OS as conventionally assessed. Many of these trials allowed crossover upon progression and, in some instances, other agents with similar biological activity were available to patients after they withdrew from the clinical trial. These facts may have made it more difficult to detect an OS benefit. For the clinician, this makes it challenging to determine the real benefit of these drugs to the patient. The four FDA-approved anti-VEGF agents include three oral tyrosine kinase inhibitors: pazopanib, sorafenib and sunitinib; and an anti-VEGF monoclonal antibody, bevacizumab. Axitinib is a newer, highly selective, and more potent inhibitor of VEGF receptors 1, 2, and 3 and has been approved by the FDA for the treatment of advanced renal cell carcinoma after the failure of one prior systemic therapy.[24]

Sunitinib

Sunitinib and the combination of bevacizumab plus interferon-alpha have each been associated with longer PFS than interferon-alpha alone in randomized, controlled trials. Sunitinib is an orally available multikinase inhibitor (VEGFR-1, VEGFR-2, PDGFR, c-Kit). In 750 previously untreated patients, all of whom had clear-cell kidney cancer, a phase III trial compared sunitinib with interferon-alpha.[25] Sunitinib as first-line systemic therapy was associated with a median PFS of 11 months compared with 5 months for interferon-alpha. The HR for progression was 0.42 (95% CI, 0.32–0.54; P < .001).[25][Level of evidence: 1iiDiii] However, the analysis for OS showed a strong but statistically nonsignificant trend to improved survival (26.4 months vs. 21.8 months, HR, 0.82; 95% CI, 0.669–1.001; P = .051).[26][Level of evidence: 1iiDiii] Bevacizumab, a monoclonal antibody that binds to and neutralizes circulating VEGF protein, delayed progression of clear-cell renal cell carcinoma when compared with placebo in patients with disease refractory to biological therapy.[27] Similarly, bevacizumab plus interferon-alpha as first-line therapy resulted in longer PFS but not OS compared with interferon alpha alone in two similarly designed, randomized, controlled trials.[28][29]

Axitinib

Axitinib was shown to prolong progression of disease when used as second-line systemic therapy. A randomized, controlled trial of 723 patients conducted at 175 sites in 22 countries evaluated axitinib versus sorafenib as treatment for renal cell carcinoma with a clear-cell component that had progressed during or after first-line treatment with sunitinib (54%), cytokines (35%), bevacizumab plus interferon (8%), or temsirolimus (3%).[24][30] The primary endpoint was PFS, and the data were analyzed when disease in 88% of the axitinib patients and 90% of the sorafenib patients had progressed, while 58% and 59%, respectively, had died.

Median PFS was 8.3 months for axitinib and 5.7 months for sorafenib (HR, 0.656; 95% CI, 0.552–0.779, P < .0001 for progression death using a one-sided log-rank test and a threshold of P < .025 for significance). Median OS was 20.1 months with axitinib compared with 19.2 months with sorafenib (HR, 0.969; 95% CI, 0.80–1.17, P = .374). However, the largest benefit was seen in patients who received cytokines as first-line therapy and whose median PFS was 12.2 months with axitinib compared with 8.2 months with sorafenib (P < .0001), while median OS was 29.4 months with axitinib compared with 27.8 months with sorafenib (HR, 0.81; 95% CI, 0.5501.19; P = .144). In contrast, in patients who had previously received sunitinib, axitinib was associated with a 2.1-month increase in PFS compared with sorafenib (6.5 months vs. 4.4 months, one-sided P = .002), but median OS was nearly identical: 15.2 months with axitinib compared with 16.5 months with sorafenib (HR, 1.0; 95% CI, 0.782–1.270; P = .49).[30]

Comparing the toxicity of the axitinib and sorafenib regimens is complicated because the axitinib arm included a dose-escalation component such that only those patients who tolerated the lower dose were subsequently given the higher doses. Hypertension, nausea, dysphonia, and hypothyroidism were more common with axitinib, whereas palmar-plantar erythrodysesthesia, alopecia, and rash were more common with sorafenib.[24][30]

Pazopanib

Pazopanib is an orally available multikinase inhibitor (VEGFR-1, VEGFR-2, VEGFR-3, PDGFR, and c-KIT) and has also been approved for the treatment of patients with advanced renal cell carcinoma.[31]

Pazopanib was evaluated in a randomized, placebo-controlled, international trial (VEG015192 [NCT00334282]) that enrolled 435 patients with clear cell or predominantly clear-cell renal cell carcinoma.[32] Nearly half of the patients had previously received cytokine therapy, although the remainder of them were treatment naïve. PFS was significantly prolonged in the pazopanib arm at 9.2 months compared with 4.2 months in the placebo arm. The HR for progression was 0.46 (95% CI, 0.34–0.62; P < .0001), and the median duration of response was longer than 1 year.

Pazopanib was also compared with sunitinib in a randomized controlled trial (NCT00720941) that enrolled 1,110 patients who had metastatic renal cell carcinoma with a clear-cell component in a 1:1 ratio.[33] The primary endpoint was PFS. The study was powered to assess the noninferiority of pazopanib. Results were reported when there was disease progression in 336 of 557patients (60%) who received pazopanib and 323 of 553 patients (58%) who received sunitinib. The median PFS time was 8.4 months for those in the pazopanib arm and 9.5 months for those in the sunitinib arm (HR, 1.05; CI, .9–1.22). There was no difference in OS (HR, 0.91; 95% CI, .76–1.08). Although quality of life was compared in the study, differences in the scheduled administration of the medications made this comparison difficult to interpret.

Sorafenib

Sorafenib is an orally available multikinase inhibitor (cRAF, bRAF, KIT, FLT-3, VEGFR-2, VEGFR-3, and PDGFR-β) and has also been approved for the treatment of patients with advanced renal cell carcinoma.[31]

In an international, multicenter, randomized trial with the primary endpoints of PFS and OS, 769 patients were stratified by the Memorial Sloan-Kettering Cancer Center prognostic risk category and by country and were randomly assigned to receive either sorafenib (400 mg bid) or a placebo. Approximately 82% of the patients had received prior IL-2 and/or interferon-alpha in both arms of the study. The median PFS for patients randomly assigned to sorafenib was 167 days compared with 84 days for patients randomly assigned to placebo (P < .001). The estimated HR for the risk of progression with sorafenib compared with a placebo was 0.44 (95% CI, 0.35–0.55). There was no significant difference in OS.[31][Level of evidence: 1iDiii] A subsequent phase II study of 189 patients randomly assigned to either sorafenib or interferon-alpha reported no difference (5.7 months vs. 5.6 months) in PFS, but sorafenib was associated with better quality of life than interferon-alpha.[34]

Chemotherapy

Responses to cytotoxic chemotherapy generally have not exceeded 10% for any regimen that has been studied in adequate numbers of patients.

Treatment Options

Because of the lack of curative therapy for metastatic disease and the promise of targeted therapies, patients should be considered for the many ongoing clinical trials testing single or combination therapies, including the following:

  1. Radical nephrectomy (for T4, M0 lesions).
  2. Cytoreductive nephrectomy (for any T, M1 lesions).[2][3]
  3. Temsirolimus.[22]
  4. Sunitinib.[25][26]
  5. Pazopanib.[32]
  6. Bevacizumab with or without interferon-alpha.[27][28][29][35]
  7. Everolimus (for patients who have previously been treated with sunitinib and/or sorafenib).[23]
  8. Sorafenib.[34][36]
  9. Axitinib.[30]
  10. Interferon-alpha.[11][21][37][38]
  11. IL-2.[11][17][18]
  12. Palliative EBRT.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV renal cell cancer and recurrent renal cell cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Kidney. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 479-89.

  2. Flanigan RC, Salmon SE, Blumenstein BA, et al.: Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med 345 (23): 1655-9, 2001.

  3. Mickisch GH, Garin A, van Poppel H, et al.: Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet 358 (9286): 966-70, 2001.

  4. Murthy SC, Kim K, Rice TW, et al.: Can we predict long-term survival after pulmonary metastasectomy for renal cell carcinoma? Ann Thorac Surg 79 (3): 996-1003, 2005.

  5. van der Poel HG, Roukema JA, Horenblas S, et al.: Metastasectomy in renal cell carcinoma: A multicenter retrospective analysis. Eur Urol 35 (3): 197-203, 1999.

  6. Eggener SE, Yossepowitch O, Kundu S, et al.: Risk score and metastasectomy independently impact prognosis of patients with recurrent renal cell carcinoma. J Urol 180 (3): 873-8; discussion 878, 2008.

  7. Kwak C, Park YH, Jeong CW, et al.: Metastasectomy without systemic therapy in metastatic renal cell carcinoma: comparison with conservative treatment. Urol Int 79 (2): 145-51, 2007.

  8. Russo P, O'Brien MF: Surgical intervention in patients with metastatic renal cancer: metastasectomy and cytoreductive nephrectomy. Urol Clin North Am 35 (4): 679-86; viii, 2008.

  9. Hofmann HS, Neef H, Krohe K, et al.: Prognostic factors and survival after pulmonary resection of metastatic renal cell carcinoma. Eur Urol 48 (1): 77-81; discussion 81-2, 2005.

  10. Wroński M, Arbit E, Russo P, et al.: Surgical resection of brain metastases from renal cell carcinoma in 50 patients. Urology 47 (2): 187-93, 1996.

  11. Coppin C, Porzsolt F, Awa A, et al.: Immunotherapy for advanced renal cell cancer. Cochrane Database Syst Rev (1): CD001425, 2005.

  12. Rosenberg SA, Lotze MT, Muul LM, et al.: A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med 316 (15): 889-97, 1987.

  13. Fisher RI, Coltman CA Jr, Doroshow JH, et al.: Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells. A phase II clinical trial. Ann Intern Med 108 (4): 518-23, 1988.

  14. Weiss GR, Margolin KA, Aronson FR, et al.: A randomized phase II trial of continuous infusion interleukin-2 or bolus injection interleukin-2 plus lymphokine-activated killer cells for advanced renal cell carcinoma. J Clin Oncol 10 (2): 275-81, 1992.

  15. Rosenberg SA, Yang JC, Topalian SL, et al.: Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA 271 (12): 907-13, 1994 Mar 23-30.

  16. Fyfe G, Fisher RI, Rosenberg SA, et al.: Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol 13 (3): 688-96, 1995.

  17. McDermott DF, Regan MM, Clark JI, et al.: Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol 23 (1): 133-41, 2005.

  18. Yang JC, Topalian SL, Parkinson D, et al.: Randomized comparison of high-dose and low-dose intravenous interleukin-2 for the therapy of metastatic renal cell carcinoma: an interim report. J Clin Oncol 12 (8): 1572-6, 1994.

  19. Sleijfer DT, Janssen RA, Buter J, et al.: Phase II study of subcutaneous interleukin-2 in unselected patients with advanced renal cell cancer on an outpatient basis. J Clin Oncol 10 (7): 1119-23, 1992.

  20. Atkins MB, Sparano J, Fisher RI, et al.: Randomized phase II trial of high-dose interleukin-2 either alone or in combination with interferon alfa-2b in advanced renal cell carcinoma. J Clin Oncol 11 (4): 661-70, 1993.

  21. Negrier S, Perol D, Ravaud A, et al.: Medroxyprogesterone, interferon alfa-2a, interleukin 2, or combination of both cytokines in patients with metastatic renal carcinoma of intermediate prognosis: results of a randomized controlled trial. Cancer 110 (11): 2468-77, 2007.

  22. Hudes G, Carducci M, Tomczak P, et al.: Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356 (22): 2271-81, 2007.

  23. Motzer RJ, Escudier B, Oudard S, et al.: Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372 (9637): 449-56, 2008.

  24. Rini BI, Escudier B, Tomczak P, et al.: Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 378 (9807): 1931-9, 2011.

  25. Motzer RJ, Hutson TE, Tomczak P, et al.: Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356 (2): 115-24, 2007.

  26. Motzer RJ, Hutson TE, Tomczak P, et al.: Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 27 (22): 3584-90, 2009.

  27. Yang JC, Haworth L, Sherry RM, et al.: A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349 (5): 427-34, 2003.

  28. Rini BI, Halabi S, Rosenberg JE, et al.: Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol 26 (33): 5422-8, 2008.

  29. Escudier B, Pluzanska A, Koralewski P, et al.: Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 370 (9605): 2103-11, 2007.

  30. Motzer RJ, Escudier B, Tomczak P, et al.: Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol 14 (6): 552-62, 2013.

  31. Nexavar® [label information]. Rockville, Md: Center for Drug Evaluation and Research, FDA, 2007. Available online. Last accessed February 9, 2012.

  32. Sternberg CN, Davis ID, Mardiak J, et al.: Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28 (6): 1061-8, 2010.

  33. Motzer RJ, Hutson TE, Cella D, et al.: Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med 369 (8): 722-31, 2013.

  34. Escudier B, Szczylik C, Hutson TE, et al.: Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma. J Clin Oncol 27 (8): 1280-9, 2009.

  35. Escudier B, Bellmunt J, Négrier S, et al.: Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol 28 (13): 2144-50, 2010.

  36. Escudier B, Eisen T, Stadler WM, et al.: Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356 (2): 125-34, 2007.

  37. Pyrhönen S, Salminen E, Ruutu M, et al.: Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer. J Clin Oncol 17 (9): 2859-67, 1999.

  38. Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Medical Research Council Renal Cancer Collaborators. Lancet 353 (9146): 14-7, 1999.


This information is provided by the National Cancer Institute.

This information was last updated on February 21, 2014.

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