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医療専門家向け Renal Cell Cancer Treatment (PDQ®)

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This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of renal cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

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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 2021:[ 1 ]

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 73% of all patients with renal cell cancer survive for 5 years.[ 3 ] 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:

参考文献
  1. American Cancer Society: Cancer Facts and Figures 2021. American Cancer Society, 2021. Available online. Last accessed June 02, 2021.[PUBMED Abstract]
  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.[PUBMED Abstract]
  3. National Cancer Institute: SEER Stat Fact Sheets: Kidney and Renal Pelvis Cancer. Bethesda, Md: National Cancer Institute. Available online. Last accessed November 06, 2020.[PUBMED Abstract]
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 the size of the mass, but size alone should not influence the treatment approach, because 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 ]

AJCC Stage Groupings and TNM Definitions

The American Joint Committee on Cancer (AJCC) has designated staging by TNM (tumor, node, metastasis) classification to define renal cell cancer.[ 5 ]

Table 1. Definitions of TNM Stage Ia
Stage TNM Definition Illustration
T = primary tumor; N = regional lymph node; M = distant metastasis.
aReprinted with permission from AJCC: Kidney. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 739–48.
I T1, N0, M0 T1 = Tumor ≤7 cm in greatest dimension, limited to the kidney.  
Stage I kidney cancer; drawing shows cancer in the left kidney and the tumor is 7 centimeters or smaller. An inset shows 7 centimeters is about the size of a peach. Also shown are fatty tissue and the right kidney.

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–T1a = Tumor ≤4 cm in greatest dimension, limited to the kidney.
–T1b = Tumor >4 cm but ≤7 cm in greatest dimension, limited to the kidney.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
Table 2. Definitions of TNM Stage IIa
Stage TNM Definition Illustration
T = primary tumor; N = regional lymph node; M = distant metastasis.
aReprinted with permission from AJCC: Kidney. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 739–48.
II T2, N0, M0 T2 = Tumor >7 cm in greatest dimension, limited to the kidney.  
Stage II kidney cancer; drawing shows cancer in the left kidney and the tumor is larger than 7 centimeters. An inset shows 7 centimeters is about the size of a peach. Also shown are the fatty tissue and right kidney.

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–T2a = Tumor >7 cm but ≤10 cm in greatest dimension, limited to the kidney.
–T2b = Tumor >10 cm, limited to the kidney.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
Table 3. Definitions of TNM Stage IIIa
Stage TNM Definition Illustration
T = primary tumor; N = regional lymph node; M = distant metastasis.
aReprinted with permission from AJCC: Kidney. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 739–48.
III T1, N1, M0 T1 = Tumor ≤7 cm in greatest dimension, limited to the kidney.  
Stage III kidney cancer; drawing shows cancer in the left kidney and in a) nearby lymph nodes, b) the renal vein, c) the structures in the kidney that collect urine, and d) the layer of fatty tissue around the kidney. Also shown are the right kidney, vena cava, and right and left adrenal glands.

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–T1a = Tumor ≤4 cm in greatest dimension, limited to the kidney.
–T1b = Tumor >4 cm but ≤7 cm in greatest dimension, limited to the kidney.
N1 = Metastasis in regional lymph node(s).
M0 = No distant metastasis.
T2, N1, M0 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.
N1 = Metastasis in regional lymph node(s).
M0 = No distant metastasis.
T3, N0, M0 T3 = Tumor extends into major veins or perinephric tissues but not into the ipsilateral adrenal gland and not beyond Gerota's fascia.
–T3a = Tumor extends into the renal vein or its segmental branches, or invades the pelvicalyceal system, or invades perirenal and/or renal sinus fat but not beyond Gerota's fascia.
–T3b = Tumor extends into the vena cava below the diaphragm.
–T3c = Tumor extends into the vena cava above the diaphragm or invades the wall of the vena cava.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
T3, N1, M0 T3 = Tumor extends into major veins or perinephric tissues but not into the ipsilateral adrenal gland and not beyond Gerota's fascia.
–T3a = Tumor extends into the renal vein or its segmental branches, or invades the pelvicalyceal system, or invades perirenal and/or renal sinus fat but not beyond Gerota's fascia.
–T3b = Tumor extends into the vena cava below the diaphragm.
–T3c = Tumor extends into the vena cava above the diaphragm or invades the wall of the vena cava.
N1 = Metastasis in regional lymph node(s).
M0 = No distant metastasis.
Table 4. Definitions of TNM Stage IVa
Stage TNM Definition Illustration
T = primary tumor; N = regional lymph node; M = distant metastasis.
aReprinted with permission from AJCC: Kidney. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 739–48.
IV T4, Any N, M0 T4 = Tumor invades beyond Gerota's fascia (including contiguous extension into the ipsilateral adrenal gland).  
Stage IV kidney cancer; drawing shows cancer that has spread beyond the layer of fatty tissue around the left kidney to a) the adrenal gland above the left kidney. Also shown are the lymph nodes, right adrenal gland, and right kidney. An inset shows b) other parts of the body where kidney cancer may spread, including the brain, lung, liver, adrenal gland, bone, and distant lymph nodes.

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NX = Regional lymph nodes cannot be assessed.
N0 = No regional lymph node metastasis.
N1 = Metastasis in regional lymph node(s).
M0 = No distant metastasis.
Any T, Any N, M1 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 ≤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's fascia.
–T3a = Tumor extends into the renal vein or its segmental branches, or invades the pelvicalyceal system, or invades perirenal and/or renal sinus fat but not beyond Gerota's fascia.
–T3b = Tumor extends into the vena cava below the diaphragm.
–T3c = Tumor extends into the vena cava above the diaphragm or invades the wall of the vena cava.
T4 = Tumor invades beyond Gerota's fascia (including contiguous extension into the ipsilateral adrenal gland).
NX = Regional lymph nodes cannot be assessed.
N0 = No regional lymph node metastasis.
N1 = Metastasis in regional lymph node(s).
M1 = Distant metastasis.
参考文献
  1. Bassil B, Dosoretz DE, Prout GR: Validation of the tumor, nodes and metastasis classification of renal cell carcinoma. J Urol 134 (3): 450-4, 1985.[PUBMED Abstract]
  2. Golimbu M, Joshi P, Sperber A, et al.: Renal cell carcinoma: survival and prognostic factors. Urology 27 (4): 291-301, 1986.[PUBMED Abstract]
  3. Robson CJ, Churchill BM, Anderson W: The results of radical nephrectomy for renal cell carcinoma. J Urol 101 (3): 297-301, 1969.[PUBMED Abstract]
  4. Consensus conference. Magnetic resonance imaging. JAMA 259 (14): 2132-8, 1988.[PUBMED Abstract]
  5. Kidney. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 739–48.[PUBMED Abstract]
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 Treatment

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's fascia, with or without a regional lymph node dissection. Some, but not all, surgeons believe the radical operation yields superior results.

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 ]

In patients who are not candidates for surgery, external-beam radiation therapy (EBRT) or arterial embolization can provide palliation.

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

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

参考文献
  1. Kidney. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 739–48.[PUBMED Abstract]
  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.[PUBMED Abstract]
  3. Thrasher JB, Robertson JE, Paulson DF: Expanding indications for conservative renal surgery in renal cell carcinoma. Urology 43 (2): 160-8, 1994.[PUBMED Abstract]
  4. deKernion JB, Berry D: The diagnosis and treatment of renal cell carcinoma. Cancer 45 (7 Suppl): 1947-56, 1980.[PUBMED Abstract]
  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.[PUBMED Abstract]
Stage II Renal Cell Cancer Treatment

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's 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

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

参考文献
  1. Kidney. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 739–48.[PUBMED Abstract]
  2. Phillips E, Messing EM: Role of lymphadenectomy in the treatment of renal cell carcinoma. Urology 41 (1): 9-15, 1993.[PUBMED Abstract]
  3. deKernion JB, Berry D: The diagnosis and treatment of renal cell carcinoma. Cancer 45 (7 Suppl): 1947-56, 1980.[PUBMED Abstract]
Stage III Renal Cell Cancer Treatment

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's 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 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 ]

In patients who are not candidates for surgery, arterial embolization can provide palliation.

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's 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 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 ]

In patients who are not candidates for surgery, arterial embolization can provide palliation.

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 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

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

参考文献
  1. Kidney. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 739–48.[PUBMED Abstract]
  2. Phillips E, Messing EM: Role of lymphadenectomy in the treatment of renal cell carcinoma. Urology 41 (1): 9-15, 1993.[PUBMED Abstract]
  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.[PUBMED Abstract]
  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.[PUBMED Abstract]
  5. deKernion JB: Management of renal adenocarcinoma. In: deKernion JB, Paulson DF, eds.: Genitourinary Cancer Management. Lea and Febiger, 1987, pp 187-217.[PUBMED Abstract]
  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.[PUBMED Abstract]
  7. deKernion JB, Berry D: The diagnosis and treatment of renal cell carcinoma. Cancer 45 (7 Suppl): 1947-56, 1980.[PUBMED Abstract]
  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.[PUBMED Abstract]
Stage IV and Recurrent Renal Cell Cancer Treatment

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 previous 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

In patients without metastatic disease, resection of the primary tumor, when feasible, is standard practice. In patients with unresectable and/or metastatic cancers, 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.

Cytoreductive nephrectomy

In the era before targeted antiangiogenic therapies and immune checkpoint inhibitors, two randomized studies demonstrated an overall survival (OS) benefit in selected patients who underwent initial cytoreductive nephrectomy before the administration of interferon-alpha.[ 2 ][ 3 ] However, there is evidence that undergoing cytoreductive nephrectomy before antiangiogenic therapy does not provide a survival benefit to patients with intermediate- and poor-risk disease. Cytoreductive nephrectomy for good-risk patients has not been studied in a randomized controlled trial in the era of targeted therapies and immunotherapy. The limited data available from retrospective nonrandomized studies suggest a benefit in good-risk patients in the current era of targeted therapies.

Evaluating the effectiveness of cytoreductive nephrectomy before targeted therapy, the CARMENA (NCT00930033) trial reported no benefit from undergoing cytoreductive nephrectomy before receiving treatment with sunitinib, an oral antiangiogenic tyrosine kinase inhibitor.[ 4 ] This study enrolled only patients with intermediate- (57%) and poor-risk (43%) disease, whereas a previous retrospective study found that cytoreductive nephrectomy only benefited good- and intermediate-risk patients in the sunitinib era. Similarly, the positive trials in the interferon era were restricted to patients who were asymptomatic or minimally symptomatic, with a performance status (PS) rating of 0 or 1, according to the Eastern Cooperative Oncology Group (ECOG) rating scale; these patients were also considered fit candidates for postoperative immunotherapy.

A multicenter analysis of 351 patients with metastatic renal cell carcinoma was conducted to assess the impact of cytoreductive nephrectomy. The study evaluated patients who received systemic therapy and compared outcomes of those who underwent cytoreductive nephrectomy with those who did not. The median OS was 38.1 months for patients who underwent nephrectomy compared with 16.4 months for those treated with systemic therapy alone (P = .03). However, the survival benefit was limited to patients with an ECOG PS rating of 0 to 1 and good- or intermediate-risk disease.[ 5 ] Interpretation of the study is limited by selection bias because patients were not randomly assigned to the nephrectomy group. Whether there is a benefit from cytoreductive nephrectomy for patients who are not subsequently treated with systemic therapy has not been tested in the current era.

Randomized controlled trials of cytoreductive nephrectomy:

A randomized, controlled, noninferiority trial of 450 patients compared the outcomes of patients who received sunitinib alone with those who received cytoreductive nephrectomy followed by sunitinib. The trial was designed to enroll 576 individuals, so it was underpowered.[ 4 ] In this study, 43% of the patients had poor-risk disease and 57% had intermediate-risk disease.

Randomized controlled trials of interferon with or without preceding cytoreductive nephrectomy:

Two randomized studies demonstrated an OS benefit in selected patients who underwent initial cytoreductive nephrectomy before the administration of interferon-alpha.[ 2 ][ 3 ]

Resection of oligometastatic disease

Selected patients with solitary or a limited number of distant metastases can achieve prolonged survival with nephrectomy and surgical resection of the metastases.[ 6 ][ 7 ][ 8 ][ 9 ][ 10 ][ 11 ] Even patients with brain metastases had similar results.[ 12 ] 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.

Combined Immune Checkpoint Inhibitors and Antiangiogenic Targeted Therapies

After immune checkpoint inhibitors and antiangiogenic targeted therapies were found to improve outcomes, the combination of these two approaches has been studied in clinical trials and shown to result in longer OS when compared with monotherapy.

Pembrolizumab plus axitinib

Evidence (pembrolizumab plus axitinib):

  1. An open-label, phase III randomized controlled trial (NCT02853331) comparing sunitinib with the combination of pembrolizumab and axitinib enrolled 861 patients who had received no previous systemic therapy for metastatic disease.[ 13 ]

Avelumab plus axitinib

Evidence (avelumab plus axitinib):

  1. An open-label phase III randomized trial (NCT02684006) compared the combination of avelumab and axitinib with sunitinib monotherapy in 560 patients with previously untreated stage IV programmed cell death-ligand-1 (PD-L1)–positive renal cell carcinoma (the entire study population was 886 patients, including those who were PD-L1 negative).[ 14 ] This trial specified two primary endpoints: PFS and OS among patients with PD-L1-positive tumors. PFS among the entire study population was a secondary endpoint.

Immunotherapy

Immune checkpoint inhibitors

Immune checkpoint inhibitors are drugs that block certain proteins that inhibit the response to cancer by the immune system. These proteins down-regulate T-lymphocyte activity and can prevent these cells from killing cancer cells. By reducing the activity of these inhibitory proteins, immune checkpoint inhibitors increase the immune response to cancer. Immune checkpoint proteins that are targeted by this class of drugs include programmed cell death-1 (PD-1), PD-L1, and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4).

Ipilimumab plus nivolumab

The combination of ipilimumab and nivolumab was shown to prolong OS when compared with sunitinib as first-line systemic therapy for advanced-stage renal cell carcinoma in a randomized, controlled trial.[ 15 ] Both drugs are immune checkpoint inhibitors. Ipilimumab is an antibody that targets CTLA-4. Nivolumab is an antibody that targets PD-1.

Evidence (ipilimumab plus nivolumab):

  1. A randomized controlled trial compared the combination of these two drugs with sunitinib. Nivolumab (3 mg/kg) and ipilimumab (1 mg/kg) were given every 3 weeks for four doses followed by maintenance nivolumab (3 mg/kg) every 2 weeks. Sunitinib was given at a dose of 50 mg once daily for the first 4 weeks of a repeating 6-week cycle (i.e., each cycle consisted of 4 weeks taking the drug followed by a 2-week break). Treatment continued until disease progression unless adverse events or withdrawal of consent led to discontinuation. The coprimary endpoints were OS, PFS, and objective response rate in patients with intermediate- or poor-risk disease. Of note, because there were three primary endpoints, the overall alpha level of 0.05 was divided among the three endpoints. This meant that the P-value cutoffs for significance were 0.001 for response rate, 0.009 for PFS, and 0.04 for OS. The trial enrolled 1,096 patients, and 847 had intermediate- or poor-risk disease.

Nivolumab

Nivolumab is the only treatment that has shown prolonged OS in patients who have previously received antiangiogenic therapy. Nivolumab is a fully human antibody that blocks ligand activation of the PD-1. By blocking the interaction between PD-1 and PD-1 ligands 1 and 2, nivolumab blocks a pathway that inhibits the cellular immune response and restores cellular immunity.

Evidence (nivolumab):

  1. A phase II trial showed promising results and no dose response with nivolumab, which was dosed at 0.3 mg/kg, 2 mg/kg, or 10 mg/kg and administered every 3 weeks.[ 16 ]
  2. A randomized controlled trial compared nivolumab at a dose of 3 mg/kg every 2 weeks with everolimus at a dose of 10 mg daily.[ 17 ] The trial randomly assigned 821 patients with metastatic renal cell carcinoma and a clear cell component who had previously received one or two antiangiogenic regimens.

    It is not clear whether the dose of 3 mg/kg every 2 weeks used in the phase III trial offers any advantage over the dose of 2 mg/kg every 3 weeks used in the phase II trial; however, the latter dose offers substantial cost savings.

Cytokine therapy

Interferon-alpha and interleukin-2 (IL-2)

Cytokine therapy with interferon-alpha or 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.[ 18 ] In general, these patients have nonbulky pulmonary or soft tissue metastases with excellent PS ratings of 0 or 1, 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 administered 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.[ 18 ][Level of evidence: 1iiA]

High-dose IL-2 produces an overall response rate similar to that of interferon-alpha, but approximately 5% of the patients have shown durable complete remissions.[ 19 ][ 20 ][ 21 ][ 22 ][ 23 ][ 24 ] No randomized controlled trial of IL-2 has ever shown a longer survival result. 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 show 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 in terms of survival or QOL.[ 25 ] Outpatient subcutaneous administration has also demonstrated responses with acceptable toxic effects but, again, with unclear survival or QOL benefit.[ 26 ] 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.[ 27 ][ 28 ]

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 that target 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.

Anti-vascular endothelial growth factor (VEGF) and multi-target tyrosine kinase inhibitors

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 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 previously received systemic therapy.[ 29 ]

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).

Evidence (sunitinib):

  1. In 750 previously untreated patients, all of whom had clear cell kidney cancer, a phase III trial compared sunitinib with interferon-alpha.[ 30 ]

    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.[ 32 ] 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.[ 33 ][ 34 ]

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.[ 35 ]

Evidence (pazopanib):

  1. 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.[ 36 ] Nearly 50% of the patients had previously received cytokine therapy, although the remainder of them were treatment naïve.
  2. 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.[ 37 ] 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 557 patients (60%) who received pazopanib and in 323 of 553 patients (58%) who received sunitinib.
  3. A subsequent double-blind, randomized, controlled, cross-over trial compared sunitinib followed by pazopanib with pazopanib followed by sunitinib; the primary endpoint was patient preference for one drug over the other.[ 38 ] Patients were treated for 10 weeks with either sunitinib or pazopanib, followed by a 2-week washout period, followed by 10 more weeks of treatment with the other drug. Preference was assessed at the end of the second 10-week treatment period. This study design created possible bias in favor of pazopanib.

    Although the typical regimen for administering sunitinib is a 6-week cycle of 4 weeks on the drug and 2 weeks off the drug, the Patient Preference Study of Pazopanib Versus Sunitinib in Advanced or Metastatic Kidney Cancer (PISCES [NCT01064310]) chose a treatment period of 10 weeks rather than 12 weeks. Because of this treatment-period change, the 10 weeks of sunitinib treatment included 4 weeks on the drug, followed by 2 weeks off the drug, followed by 4 more weeks on the drug. Patients assigned to pazopanib followed by sunitinib had their preference for treatment assessed at the end of the second 4-weeks-on-the-drug period during which they took sunitinib daily for 28 days. At that point, the sunitinib side effects became the most severe. The expected result from an assessment conducted at the end of a 6-week treatment cycle versus the 4-week treatment cycle would be greatly abated side effects.

    In addition, the 2-week washout period that occurred between the two 10-week treatment periods was a true break from treatment for patients assigned to take pazopanib first; however, for the patients taking sunitinib, the 2-week washout period was just the completion of their second 6-week treatment cycle. In other words, patients assigned to pazopanib first had a true 2-week break from treatment, and their drug preference was assessed at the peak period of toxic effects from sunitinib; however, the patients assigned to sunitinib first had no true treatment break before starting pazopanib and may have had less opportunity to recover from the side effects of sunitinib.

Cabozantinib

Cabozantinib is an oral tyrosine kinase inhibitor of the MET, AXL, and VEGF receptors. After a phase I trial showed activity against renal cell carcinoma, a phase III trial assessed the activity of cabozantinib in the second-line setting in a randomized controlled trial.

Evidence (cabozantinib):

  1. The METEOR (NCT01865747) trial randomly assigned 658 patients who had previously been treated with a VEGF tyrosine kinase inhibitor to receive either cabozantinib (60 mg qd) or everolimus (10 mg qd).[ 39 ][ 40 ] Doses were reduced in 60% of the patients receiving cabozantinib compared with 25% of the patients assigned to everolimus.
  2. A subsequent trial compared cabozantinib with sunitinib in the first-line setting, randomly assigning 157 patients with intermediate- or poor-risk metastatic renal cell carcinoma to cabozantinib or sunitinib.[ 42 ][ 43 ]
    1. Adverse events were seen in more than 95% of the patients.
    2. With a median follow-up of 34.5 months, there was no significant difference in OS between the two arms, and the OS curves crossed multiple times.
    3. PFS, however, was longer with cabozantinib (8.6 months vs. 5.3 months [HR, 0.48; 95% CI, 0.31–0.74]), demonstrating that PFS is an inadequate surrogate for OS.[ 42 ][ 43 ][Level of evidence: 1iiDiii]

Axitinib

Axitinib has been shown to prolong PFS when used as second-line systemic therapy.

Evidence (axitinib):

  1. 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%).[ 29 ][ 44 ] 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.

    Comparing the toxicity of the axitinib and sorafenib regimens is complicated because the axitinib arm included a dose-escalation component, and 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.[ 29 ][ 44 ]

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.[ 35 ]

Evidence (sorafenib):

  1. 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 IL-2 previously and/or interferon-alpha in both arms of the study.
  2. A subsequent phase II study randomly assigned 189 patients to either sorafenib or interferon-alpha.[ 45 ]

Mammalian target of rapamycin (mTOR) inhibitors

Temsirolimus

Temsirolimus is an intravenously administered mTOR inhibitor.

Evidence (temsirolimus):

  1. A phase III randomized controlled trial enrolled intermediate- and poor-risk patients with a variety of subtypes of renal cell carcinoma. The trial was not restricted to clear cell kidney cancer.

Everolimus

Everolimus is an orally administered mTOR inhibitor.

Evidence (everolimus):

  1. Everolimus was evaluated in a double-blind, randomized, placebo-controlled phase III trial that 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, sorafenib, or both drugs.

Combined Therapy With Multi-Target Tyrosine Kinase Inhibitors and MTOR Inhibitors

Lenvatinib plus everolimus

Lenvatinib is a multi-target tyrosine kinase inhibitor with activity against VEGFR-1, VEGFR-2, and VEGFR-3, with inhibitory activity against fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3, and FGFR4), PDGFRα, RET, and KIT.

Evidence (lenvatinib plus everolimus):

  1. The combination of lenvatinib plus everolimus was compared with each medication as a single agent in a randomized, controlled phase II study of 153 subjects with advanced-stage renal cell carcinoma who had received previous antiangiogenic therapy.[ 48 ] The primary endpoint was PFS.

    All patients experienced adverse events and almost all of these were judged to be related to treatment. Seventy-one percent of patients had adverse events that were grade 3 or higher. The most common toxicities in the combination arm were diarrhea, hypertension, fatigue, loss of appetite, vomiting, and cough. One patient in the combination arm died of a cerebral hemorrhage that was thought to be related to treatment.

Chemotherapy

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

Treatment Options

First-line therapy:

  1. Radical nephrectomy (for T4, M0 lesions).
  2. Cytoreductive nephrectomy (for any T, M1 lesions in patients with good-risk disease).[ 2 ][ 3 ][ 4 ][ 5 ]
  3. Ipilimumab plus nivolumab for patients with intermediate-risk or poor-risk disease.[ 15 ]
  4. Pembrolizumab plus axitinib.[ 13 ]
  5. Cabozantinib for patients with intermediate- or poor-risk disease.[ 42 ][ 43 ]
  6. Avelumab plus axitinib.[ 14 ]
  7. Sunitinib.[ 30 ][ 31 ][ 37 ][ 38 ]
  8. Pazopanib.[ 36 ][ 37 ][ 38 ]
  9. Temsirolimus.[ 46 ]
  10. Bevacizumab with or without interferon-alpha.[ 32 ][ 33 ][ 34 ][ 49 ]
  11. Interferon-alpha.[ 18 ][ 28 ][ 50 ][ 51 ]
  12. IL-2.[ 18 ][ 24 ][ 25 ]
  13. Palliative EBRT.

Second-line therapy:

  1. Nivolumab (for patients who have previously been treated with a sunitinib, pazopanib, sorafenib, and/or axitinib).[ 16 ]
  2. Lenvatinib plus everolimus in patients previously treated with sunitinib, pazopanib, cabozantinib, axitinib, or sorafenib.[ 48 ]
  3. Cabozantinib (for patients who have previously been treated with sunitinib, pazopanib, sorafenib, or axitinib).[ 39 ]
  4. Axitinib.[ 44 ]
  5. Everolimus (for patients who have previously been treated with sunitinib and/or sorafenib).[ 47 ]
  6. Sorafenib.[ 45 ][ 52 ]
  7. Palliative EBRT.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

参考文献
  1. Kidney. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 739–48.[PUBMED Abstract]
  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.[PUBMED Abstract]
  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.[PUBMED Abstract]
  4. Méjean A, Ravaud A, Thezenas S, et al.: Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma. N Engl J Med 379 (5): 417-427, 2018.[PUBMED Abstract]
  5. Mathieu R, Pignot G, Ingles A, et al.: Nephrectomy improves overall survival in patients with metastatic renal cell carcinoma in cases of favorable MSKCC or ECOG prognostic features. Urol Oncol 33 (8): 339.e9-15, 2015.[PUBMED Abstract]
  6. 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.[PUBMED Abstract]
  7. 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.[PUBMED Abstract]
  8. 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.[PUBMED Abstract]
  9. 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.[PUBMED Abstract]
  10. 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.[PUBMED Abstract]
  11. 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.[PUBMED Abstract]
  12. 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.[PUBMED Abstract]
  13. Rini BI, Plimack ER, Stus V, et al.: Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med 380 (12): 1116-1127, 2019.[PUBMED Abstract]
  14. Motzer RJ, Penkov K, Haanen J, et al.: Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med 380 (12): 1103-1115, 2019.[PUBMED Abstract]
  15. Motzer RJ, Tannir NM, McDermott DF, et al.: Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med 378 (14): 1277-1290, 2018.[PUBMED Abstract]
  16. Motzer RJ, Rini BI, McDermott DF, et al.: Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial. J Clin Oncol 33 (13): 1430-7, 2015.[PUBMED Abstract]
  17. Motzer RJ, Escudier B, McDermott DF, et al.: Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med 373 (19): 1803-13, 2015.[PUBMED Abstract]
  18. Coppin C, Porzsolt F, Awa A, et al.: Immunotherapy for advanced renal cell cancer. Cochrane Database Syst Rev (1): CD001425, 2005.[PUBMED Abstract]
  19. 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.[PUBMED Abstract]
  20. Fisher RI, Coltman CA, 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.[PUBMED Abstract]
  21. 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.[PUBMED Abstract]
  22. 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.[PUBMED Abstract]
  23. 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.[PUBMED Abstract]
  24. 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.[PUBMED Abstract]
  25. 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.[PUBMED Abstract]
  26. 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.[PUBMED Abstract]
  27. 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.[PUBMED Abstract]
  28. 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.[PUBMED Abstract]
  29. 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.[PUBMED Abstract]
  30. 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.[PUBMED Abstract]
  31. 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.[PUBMED Abstract]
  32. 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.[PUBMED Abstract]
  33. 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.[PUBMED Abstract]
  34. 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.[PUBMED Abstract]
  35. Nexavar® [label information]. Rockville, Md: Center for Drug Evaluation and Research, FDA, 2007. Available online. Last accessed February 19, 2021.[PUBMED Abstract]
  36. 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.[PUBMED Abstract]
  37. 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.[PUBMED Abstract]
  38. Escudier B, Porta C, Bono P, et al.: Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES Study. J Clin Oncol 32 (14): 1412-8, 2014.[PUBMED Abstract]
  39. Choueiri TK, Escudier B, Powles T, et al.: Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med 373 (19): 1814-23, 2015.[PUBMED Abstract]
  40. Choueiri TK, Escudier B, Powles T, et al.: Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol 17 (7): 917-927, 2016.[PUBMED Abstract]
  41. Motzer RJ, Escudier B, Powles T, et al.: Long-term follow-up of overall survival for cabozantinib versus everolimus in advanced renal cell carcinoma. Br J Cancer 118 (9): 1176-1178, 2018.[PUBMED Abstract]
  42. Choueiri TK, Halabi S, Sanford BL, et al.: Cabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial. J Clin Oncol 35 (6): 591-597, 2017.[PUBMED Abstract]
  43. Choueiri TK, Hessel C, Halabi S, et al.: Cabozantinib versus sunitinib as initial therapy for metastatic renal cell carcinoma of intermediate or poor risk (Alliance A031203 CABOSUN randomised trial): Progression-free survival by independent review and overall survival update. Eur J Cancer 94: 115-125, 2018.[PUBMED Abstract]
  44. 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.[PUBMED Abstract]
  45. 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.[PUBMED Abstract]
  46. 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.[PUBMED Abstract]
  47. 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.[PUBMED Abstract]
  48. Motzer RJ, Hutson TE, Glen H, et al.: Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol 16 (15): 1473-1482, 2015.[PUBMED Abstract]
  49. 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.[PUBMED Abstract]
  50. 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.[PUBMED Abstract]
  51. 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.[PUBMED Abstract]
  52. 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.[PUBMED Abstract]
Changes to This Summary (03/17/2021)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

General Information About Renal Cell Cancer

Updated statistics with estimated new cases and deaths for 2021 (cited American Cancer Society as reference 1).

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of renal cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

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PDQ® Adult Treatment Editorial Board. PDQ Renal Cell Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/kidney/hp/kidney-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389256]

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