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This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of renal cell cancer. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.
Information about the following is included in this summary:
This summary 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.
Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.
This summary is available in a patient version, written in less technical language, and in Spanish.
Note: Estimated new cases and deaths from renal cell (kidney and renal pelvis) cancer in the United States in 2009: [1]
Renal cell cancer, also called renal adenocarcinoma, or hypernephroma, can often be cured if it is diagnosed and treated when still localized to the kidney and to the immediately surrounding tissue. The probability of cure is directly related to the stage or degree of tumor dissemination. Even when regional lymphatics or blood vessels are involved with tumor, a significant number of patients can achieve prolonged survival and probable cure. [2] When distant metastases are present, disease-free survival is poor; however, occasional selected patients will survive after surgical resection of all known tumor. Because a majority of patients are diagnosed when the tumor is still relatively localized and amenable to surgical removal, approximately 40% of all patients with renal cancer survive for 5 years. Occasionally, patients with locally advanced or metastatic disease may exhibit indolent courses lasting several years. Late tumor recurrence many years after initial treatment also occasionally occurs.
Renal cell cancer is one of the few tumors in which well-documented cases of spontaneous tumor regression in the absence of therapy exist, but this occurs very rarely and may not lead to long-term survival. 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.
(Refer to the PDQ summaries on Wilms Tumor Treatment and Transitional Cell Cancer of the Renal Pelvis and Ureter Treatment for more information.)
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. [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]
The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification. [5]
*Laterality does not affect the N classification.
If a lymph node dissection is performed, then pathologic evaluation would ordinarily include at least eight nodes.
Current treatment cures more than 50% of the 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.
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. [1] 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. [2]
Standard treatment options:
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry 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.
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. [1] 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:
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage II renal cell cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
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. [1] 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. [2]
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. [3] EBRT has been given before or after nephrectomy without conclusive evidence that this improves survival when compared with the results of surgery alone; however, it may be of benefit in selected patients with more extensive tumors. In patients who are not candidates for surgery, arterial embolization can provide palliation. In patients with stage T3b neoplasms who manifest concurrent or subsequent renal cell carcinoma in the contralateral kidney, a partial nephrectomy, when technically feasible, may be a preferred alternative to bilateral nephrectomy with dialysis or transplantation. [2] [4] [5]
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:
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage III renal cell cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)
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. Because of early reports of success, progestational agents have been administered to patients with metastatic renal cell cancer, but the response rates have been disappointingly low; therefore, no rationale currently exists for their use as anticancer therapy. Progestational agents may, however, offer subjective palliation.
Tumor embolization, external-beam radiation therapy, and nephrectomy can aid in the palliation of symptoms caused by the primary tumor or related ectopic hormone production. Minimal evidence suggests that nephrectomy induces regression of distant metastases; therefore, a nephrectomy performed with the hope that it will be followed by spontaneous regression of metastases is not advised. Spontaneous regressions occasionally occur. A prospective surveillance series of 73 patients with advanced renal cell cancer demonstrated apparent temporary objective regression in five patients (7%) without nephrectomy or any therapy. [1] 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. [2] 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. Cytoreductive nephrectomy in selected patients who will receive postoperative interferon-α may convey a modest impact on survival. (See the Cytokine therapy section below.)
Cytokine therapy has been shown to induce objective responses and have a modest impact on survival in selected patients. Interferon-alpha has approximately a 15% objective response rate in appropriately selected individuals. [3] In general, these patients have nonbulky pulmonary and/or soft tissue metastases with excellent performance status (PS) ratings of zero or one, according to the Eastern Cooperative Oncology Group 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 a hazard rate (HR) for survival of 0.78 (confidence interval [CI], 0.67–0.90) or a weighted average improvement in survival of 2.6 months. [3][Level of evidence: 1iiA]
Two randomized studies suggest that some patients may benefit from initial cytoreductive nephrectomy prior to the administration of interferon-alpha. [4] [5] In the larger study, 246 patients were randomly assigned to either undergo a nephrectomy followed by interferon or receive interferon alone. [4] The median overall survival (OS) was 11.1 months when the primary tumor was removed first (95% CI, 9.2–16.5) compared with 8.1 months (95% CI, 5.4–9.5; P = .05). In a smaller study, 85 patients with identical eligibility criteria and treatment were randomly assigned. Patients who received nephrectomy prior to interferon-alpha had a median OS of 17 months compared with an OS of 7 months in patients receiving interferon-alpha alone (HR = 0.54; 95% CI, 0.31–0.94; P = .03;). [5] Patients were highly selected with characteristics of clear cell carcinoma, small tumors, and a PS of zero to one; they were also considered to be candidates for postoperative immunotherapy. [5][Level of evidence: 1iiA]
Patients who received interleukin-2 (IL-2), with or without lymphokine-activated killer lymphocytes, appeared to have a similar overall response rate to those who received interferon-alpha, but approximately 5% of the appropriately selected patients had durable complete remissions. [6] [7] [8] [9] [10] Combinations of IL-2 and interferon have been studied but have not been shown to be better than high-dose IL-2 alone. [11] 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 can retain efficacy with fewer toxic effects, especially hypotension. [12] Outpatient subcutaneous administration has also demonstrated responses with acceptable toxic effects. [13]
Preliminary reports of agents targeting the angiogenesis pathway appear promising. Sorafenib, an orally available multikinase inhibitor (cRAF, bRAF, KIT FLT-3, VEGFT-2, VEGFR-3 and PDGFR-β), is approved for the treatment of patients with advanced renal cell carcinoma. [14] [15] In an international, multicenter randomized trial with the primary endpoints of progression-free survival 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 b.i.d.) or a placebo. Approximately 82% of the patients had received prior IL-2 and/or interferon in both arms of the study. The median progression-free survival 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). Results for OS are not yet available. [14][Level of evidence: 1iDiii]
A randomized, double-blind phase II trial compared two doses of bevacizumab, a monoclonal antibody that acts against vascular endothelial growth factor, with placebo in patients with metastatic renal cell cancer. [16] Approximately 93% of patients had received prior IL-2 therapy. Patients receiving high-dose bevacizumab had an increase in median time-to-progression compared with placebo (4.8 vs. 2.5 months; HR = 2.55; P = .001). No significant difference was observed in OS. [16][Level of evidence: 1iDii]
Early reports of other small molecule inhibitors of the angiogenesis pathway, including tyrosine kinase inhibitors of multiple receptors such as sunitinib, also suggest antitumor activity. [17] The exact mechanism is unknown. Sunitinib received accelerated approval by the Food and Drug Administration on the basis of partial response rates and duration of response rates derived from two single-arm, multicenter trials enrolling a total of 169 patients with metastatic renal cell carcinoma progressing after cytokine-based therapy. The first study showed an objective response rate (RR) of 25.5% (95% CI, 17.5–34.9); the second study had an RR of 36.5% (95% CI, 24.7–49.6). [18] [19][Level of evidence: 2Div] Data from several prospective, randomized trials with bevacizumab or sunitinib in patients with metastatic renal cancer are not yet available.
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.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage IV renal cell cancer and recurrent renal cell cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
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For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 a.m. to 4:30 p.m. A trained Cancer Information Specialist is available to answer your questions.
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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.
Updated statistics with estimated new cases and deaths for 2009 (cited American Cancer Society as reference 1).
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