Breast cancer survivor offers wisdom at Faulkner satellite center
Call 877-422-3324 today to make an appointment
Make your appointment or second opinion with Dana-Farber today to meet with an onsite specialist.
Can’t get to Boston? Explore our Online Second Opinion service to get expert advice from Dana-Farber oncologists.
Toll-Free Number866-408-DFCI (3324)
Discover the ways to give and how to get involved to support Dana-Farber.
Poet Richard Fox gains insight – and material – through cancer treatment
A family faces cancer in an unfamiliar city – with help
Choosing mastectomy or not: Studying young women's surgical choices
Jeff's targeted therapy has kept his advanced lung cancer at bay.
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.
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
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
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:
Learn more about our genitourinary cancer treatment center
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.
Referring physicians: 617-632-2682
Attn: Lank Center for Genitourinary Oncology450 Brookline Ave.
Boston, MA 02115-5450
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 (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).
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:
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:
The following tests and procedures may be used:
The prognosis (chance of recovery) and treatment options depend on the following:
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:
Cancer can spread through tissue, the lymph system, and the blood:
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.
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.
In stage I, the tumor is 7 centimeters or smaller and is found only in the kidney.
In stage II, the tumor is larger than 7 centimeters and is found only in the kidney.
In stage III:
In stage IV, cancer has spread:
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.
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.
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:
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 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 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 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.
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.
Information about clinical trials is available from the NCI Web
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.
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.
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 of stage I renal cell cancer may include the following:
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.
Treatment of stage II renal cell cancer may include the following:
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.
Treatment of stage III renal cell cancer may include the following:
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.
Treatment of stage IV and recurrentrenal cell cancer may include the following:
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.
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.
Estimated new cases and deaths from renal cell (kidney and renal pelvis) cancer in the United States in 2014:
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. 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
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.
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.
Other PDQ summaries containing information related to renal cell cancer include the following:
American Cancer Society: Cancer Facts and Figures 2014. Atlanta, Ga: American Cancer Society, 2014. Available online. Last accessed May 21, 2014.
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.
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.
The staging system for renal cell cancer is based on the degree of tumor spread
beyond the kidney. 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
The American Joint Committee on Cancer has designated staging by TNM
classification to define renal cell cancer.
Primary tumor cannot be assessed.
No evidence of primary tumor.
Tumor ≤7 cm in greatest dimension, limited to the kidney.
Tumor ≤4 cm in greatest dimension, limited to the kidney.
Tumor >4 cm but not >7 cm in greatest dimension, limited to the kidney.
Tumor >7 cm in greatest dimension, limited to the kidney.
Tumor >7 cm but ≤10 cm in greatest dimension, limited to the kidney.
Tumor >10 cm, limited to the kidney.
Tumor extends into major veins or perinephric tissues but not into the ipsilateral adrenal gland and not beyond Gerota fascia.
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.
Tumor grossly extends into the vena cava below the diaphragm.
Tumor grossly extends into the vena cava above the diaphragm or invades the wall of the vena cava.
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.
Regional lymph nodes cannot be assessed.
No regional lymph node metastasis.
Metastases in regional lymph node(s).
No distant metastasis.
T1 or T2
N0 or N1
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.
Golimbu M, Joshi P, Sperber A, et al.: Renal cell carcinoma: survival and prognostic factors. Urology 27 (4): 291-301, 1986.
Robson CJ, Churchill BM, Anderson W: The results of radical nephrectomy for renal cell carcinoma. J Urol 101 (3): 297-301, 1969.
Consensus conference. Magnetic resonance imaging. JAMA 259 (14): 2132-8, 1988.
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.
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 is defined by the American Joint Committee on Cancer's TNM classification system:
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. 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.
Standard treatment options:
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.
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.
Thrasher JB, Robertson JE, Paulson DF: Expanding indications for conservative renal surgery in renal cell carcinoma. Urology 43 (2): 160-8, 1994.
deKernion JB, Berry D: The diagnosis and treatment of renal cell carcinoma. Cancer 45 (7 Suppl): 1947-56, 1980.
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 is defined by the American Joint Committee on Cancer's TNM classification system:
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. 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.
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.
Phillips E, Messing EM: Role of lymphadenectomy in the treatment of renal cell carcinoma. Urology 41 (1): 9-15, 1993.
Stage III renal cell cancer is defined by the American Joint Committee on Cancer's TNM classification system:
Treatment information for patients whose disease has the following classification:
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. 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.
Treatment information for patients whose disease has the following classification:
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. 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
Treatment information for patients whose disease has the following classifications:
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
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.
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.
deKernion JB: Management of renal adenocarcinoma. In: deKernion JB, Paulson DF, eds.: Genitourinary Cancer Management. Philadelphia, Pa: Lea and Febiger, 1987, pp 187-217.
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.
Stage IV renal cell cancer is defined by the American Joint Committee on Cancer's TNM classification system:
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.
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.
In the larger study, 246 patients were randomly assigned to either undergo a nephrectomy followed by interferon-alpha or receive interferon-alpha alone. 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. 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.[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. Even patients with brain metastases had similar results. 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
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. 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.[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. 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. Outpatient subcutaneous administration
has also demonstrated responses with acceptable toxic effects but, again, with unclear survival or quality of life benefit. 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.
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, 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.
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. No difference in OS was reported.
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.
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. 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).[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).[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. 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.
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%). 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).
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.
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.
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. 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. 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 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.
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.[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.
Responses to cytotoxic chemotherapy generally have not exceeded 10% for any regimen that has been studied in adequate numbers of patients.
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:
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Coppin C, Porzsolt F, Awa A, et al.: Immunotherapy for advanced renal cell cancer. Cochrane Database Syst Rev (1): CD001425, 2005.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Nexavar® [label information]. Rockville, Md: Center for Drug Evaluation and Research, FDA, 2007. Available online. Last accessed February 9, 2012.
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.
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.
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.
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.
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.
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.
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 was last updated on February 21, 2014.
Our licensed social workers are here to help adult patients and their loved ones face the many new concerns and anxieties following a cancer diagnosis, offering emotional support and assistance with obtaining needed resources.
Our support groups are geared to specific cancers and methods of treatment. They give patients the opportunity to meet and share information and moral support. Our experienced, compassionate staff facilitates and guides discussion.
If you are dealing with the death of a loved one, grief can be a lonely and isolating experience. The Bereavement Program provides support to bereaved family members and friends following the death of a patient.
Concierge Services is your one-stop place to learn about Dana-Farber programs, services and resources, as well as information on getting around Boston, finding lodging or restaurants, and activities in the area.
The Expressive Arts Therapy program, sponsored by the Leonard P. Zakim Center for Integrative Therapies, provides adult patients, family members, and caregivers with a variety of options to support well-being during cancer treatment. From live music meditation to painting technique workshops, the program offers a range of creative outlets to suit every interest.
Dana-Farber and Brigham and Women's Hospital, including parking facilities, are fully accessible to people with disabilities. There are wheelchairs at the main entrance, and security staff can provide personal assistance. We also have many educational materials available in large print and audiotape formats.
The Ethics Consultation Service is available for patients and families who may be facing difficult decisions and choices regarding care. Our goal is to bring together patients, families and health care providers to talk about ethical concerns and help everyone involved arrive at a resolution that is right for all.
This comprehensive resource offers guidance, information and resources to support the entire family, including how to talk to children about cancer, advice for the well partner, and creating a support network.
Find practical tips and suggestions for individuals caring for a family member or friend with cancer, including creating a caregiving plan, finding community resources, and looking after your own well-being.
Friends' Place provides personal consultations to help cancer patients of all ages cope with changes in physical appearance that result from cancer treatment. Our experienced, compassionate team provides fittings for compression garments or breast prostheses, helps with wigs and other head coverings, and offers make-up and skincare advice.
The Friends' Corner Gift Shop, located on the first floor of the Yawkey Center for Cancer Care, offers a wide selection of unique gifts and everyday items for patients, families and staff.
Dana-Farber offers several services to help you and your family manage the financial side of cancer treatment. From creating bill payment schedules and estate planning advice to debt management and resource assistance for patients in need, our team is here for you.
Every year, thousands of patients with cancer from around the world come to Dana-Farber for their care. We provide a wide array of logistical and other services for individuals who live outside the United States.
Dana-Farber provides interpreting services for patients whose first language is not English. Interpreters may be requested for any activity, including registration, booking appointments, attending treatments and exams, support groups, and meetings with doctors and other members of your health care team.
Our nutritionists are registered dietitians who can assist you in planning an optimal diet during any stage of your cancer journey, cope with any side effects you may experience, and answer your questions about the latest findings on cancer and nutrition.
One-to-One connects adult patients, family members and caregivers with individuals who have gone through cancer themselves, providing an experienced and reassuring perspective for those facing a cancer diagnosis, treatment and recovery.
The Eleanor and Maxwell Blum Patient and Family Resource Center and its satellite resource rooms are staffed by health care professionals and provide computer stations, books, brochures, videos, and CDs to help you find information and support on a variety of issues about cancer treatment and care.
Patients websites help friends and family members stay up-to-date on their loved ones' condition and write messages of support and encouragement.
The Dana-Farber pharmacy fills prescriptions for all pediatric and adult patients. Our pharmacists are an extension of the patient care team and work closely with your physicians to provide seamless, convenient, safe care.
More than 1,200 Dana-Farber patients and their families have enjoyed free trips to baseball games, theater shows, museums, and other attractions this year through the Recreational Resources program.
The Sexual Health Program provides education, consultation and personalized rehabilitation for patients and their partners who have experienced changes in sexual health during and after cancer treatment.
Through all stages of cancer treatment and survivorship, our Spiritual Care staff is available 24 hours a day to provide emotional and spiritual support for adults and pediatric patients and family members.
Young adults with cancer face very different challenges than patients who were diagnosed earlier in childhood or later in adulthood. The Young Adult Program can help you to find the resources and expertise available at Dana-Farber to help support your cancer experience.
Integrative therapies, also known as complementary therapies, range from acupuncture and massage to nutritional guidance and music therapy. Patients treated at the Zakim Center credit its services with easing nausea, improving circulation, and reducing pain, stress, and anxiety associated with cancer treatment.
In this video, Dr. Toni Choueiri talks about his work in the Genitourinary Cancer Treatment Center at Dana-Farber/Brigham and Women's Cancer Center.