MedicineWorld.Org
Your gateway to the world of medicine
Home
News
Cancer News
About Us
Cancer
Health Professionals
Patients and public
Contact Us
Disclaimer

Renal cell cancer (kidney cancer)

From Medicineworld.org: Renal cell cancer (kidney cancer)

Cancer Main What's Cancer? Cancer News  

renal-cell-cancer
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 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 cancer survive 5 years. Occasional patients with locally advanced or metastatic disease may exhibit indolent courses lasting several years. Late tumor recurrence many years after initial treatment 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.

Incidence
Renal cell carcinoma affects about three in 10,000 people, resulting in about 31,000 new cases in the US per year. Every year, about 12,000 people in the US die from renal cell carcinoma. It is more common in men than women, usually affecting men older than 55.

Risk factors
Why the cells become cancerous is not known. A history of smoking greatly increases the risk for developing renal cell carcinoma. Some people may also have inherited an increased risk to develop renal cell carcinoma, and a family history of kidney cancer increases the risk.

People with von Hippel-Lindau disease, a hereditary disease that also affects the capillaries of the brain, commonly also develop renal cell carcinoma. Kidney disorders that require dialysis for treatment also increase the risk for developing renal cell carcinoma. Other risk factors include smoking, misuse of analgesics.

Pathology
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 2 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. The distinction 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 centimeters.

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

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

Staging work up
Once the kidney cancer is diagnosed the follwing tests are used to assess the stage of the disease,
  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
  • MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
  • Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.
  • Bone scan: A procedure to check if there are rapidly dividing cells, such as cancer cells, in the bone. A very small amount of radioactive material is injected into a vein and travels through the bloodstream. The radioactive material collects in the bones and is detected by a scanner.

Stages of renal cell cancer
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 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 (MRI) for detecting renal masses.

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification.

TNM definitions
Primary tumor (T)
  • TX: Primary tumor cannot be assessed
  • T0: No evidence of primary tumor
  • T1: Tumor 7 cm or less in greatest dimension, limited to the kidney
    • T1a: Tumor 4 cm or less in greatest dimension, limited to the kidney
    • T1b: Tumor 4 cm or more but ≤7 cm in greatest dimension, limited to the kidney
  • T2: Tumor 7 cm or more in greatest dimension, limited to the kidney
  • T3: Tumor extends into major veins or invades adrenal gland or perinephric tissues but not beyond Gerota’s fascia
    • T3a: Tumor directly invades adrenal gland or perirenal and/or renal sinus fat but not beyond Gerota’s fascia
    • T3b: Tumor grossly extends into the renal vein or its segmental (i.e., muscle-containing) branches, or the vena cava below the diaphragm
    • T3c: Tumor grossly extends into the vena cava above the diaphragm or invades the wall of the vena cava
  • T4: Tumor invades beyond Gerota’s fascia

Regional lymph nodes (N)
  • NX: Regional lymph nodes cannot be assessed
  • N0: No regional lymph node metastasis
  • N1: Metastasis in a single regional lymph node
  • N2: Metastasis in more than 1 regional lymph node

Distant metastasis (M)
  • MX: Distant metastasis cannot be assessed
  • M0: No distant metastasis
  • M1: Distant metastasis

AJCC stage groupings
Stage I
  • T1, N0, M0

Stage II
  • T2, N0, M0

Stage III
  • T1, N1, M0
  • T2, N1, M0
  • T3, N0, M0
  • T3, N1, M0
  • T3a, N0, M0
  • T3a, N1, M0
  • T3b, N0, M0
  • T3b, N1, M0
  • T3c, N0, M0
  • T3c, N1, M0

Stage IV
  • T4, N0, M0
  • T4, N1, M0
  • Any T, N2, M0
  • Any T, any N, M1

Treatment of renal cell cancer
Treatment of stage I renal cell cancer
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 who are not candidates for surgery, external-beam radiation therapy 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.

Treatment options include:
  • Radical nephrectomy.
  • Simple nephrectomy.
  • Partial nephrectomy (selected patients).
  • External-beam radiation therapy (palliative).
  • Arterial embolization (palliative).
  • Clinical trials. Information about ongoing clinical trials is available from the NCI Web site.

Treatment of stage II renal cell cancer
A surgical resection is the accepted, often curative, therapy for stage II renal cell cancer. Resection should be radical. 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. External-beam radiation therapy 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.

Treatment options include:
  • Radical nephrectomy.
  • Nephrectomy before or after external-beam radiation therapy (selected patients).
  • Partial nephrectomy (selected patients).
  • External-beam radiation therapy (palliative).
  • Arterial embolization (palliative).
  • Clinical trials.

Treatment of stage III renal cell cancer
Treatment options vary among subgroups of patients with stage III renal cell cancer

Treatment options for T3a, N0, M0
A surgical resection is the accepted, often curative, therapy for stage III renal cell cancer. Resection should be radical. 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. External-beam radiation 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 options for T3b, N0, M0
A surgical resection is the accepted, often curative, therapy for this stage of renal cell cancer. Resection should be radical. 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. External-beam radiation therapy 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.

Treatment options for the rest of stage III renal cell cancer
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 external-beam radiation therapy has not been demonstrated, but external-beam radiation therapy 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.

Treatment options for this group of patients include:
  • For T3b tumors, radical nephrectomy with renal vein and, as necessary, vena caval resection. For any T, N1-3 tumors, radical nephrectomy with lymph node dissection.
  • Preoperative embolization and radical nephrectomy.
  • External-beam radiation therapy for palliation.
  • Tumor embolization for palliation.
  • Palliative nephrectomy.
  • Preoperative or postoperative external-beam radiation therapy and radical nephrectomy.
  • Clinical trials

Treatment of stage IV and recurrent renal cell cancer
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 therapy depends on a number of factors, including previous therapy and site of recurrence, as well as individual patient considerations. Carefully selected patients appears to benefit from surgical resection of localized metastatic disease, especially if they have had a prolonged, disease-free interval since their primary treatment.

Local Therapy
Tumor embolization, external-beam radiation treatment (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 previous 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 therapy as in the larger study.[3] Patients who underwent nephrectomy previous 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, as per the Eastern Oncology Group (ECOG) rating scale; these patients were also considered to be candidates for postoperative immunotherapy.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 metastatic disease.

Cytokine Therapy
Cytokine treatment 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, as per 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 ran omized trials, with a total of 963 patients, indicated a HR for survival of 0.78 (CI, 0.67-0.90) or a weighted average improvement in survival of 2.6 months.

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. The current use of high-dose IL-2 mainly derives from the fact that it is the only systemic treatment that has been linked to inducing durable complete remissions, albeit in a small fraction (about 5%) of patients who are eligible for this therapy. The optimum dose of IL-2 is unknown. High-dose treatment may be linked to higher response rates but with more toxic effects. Low-dose inpatient regimens have activity against renal cell carcinoma with fewer toxic effects, particularly hypotension, but have not been shown to be superior to placebo or any alternative regimen with regard to survival or quality of life.[18] Outpatient subcutaneous administration has also demonstrated responses with acceptable toxic effects but, again, with unclear survival or quality of life benefit. 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.

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

Temsirolimus, 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 treatment 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 reviewed 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 therapy 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. A number of 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.

Sunitinib and the combination of bevacizumab plus interferon-alpha have each been linked to 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 was linked to 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). 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). 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 treatment. Similarly, bevacizumab plus interferon-alpha resulted in longer PFS but not OS compared with interferon-alpha alone in two similarly-designed randomized controlled trials.

Pazopanib and sorafenib are both orally available multikinase inhibitors (VEGFR-1, VEGFR-2, VEGFR-3, PDGFR, and c-KIT for pazopanib and cRAF, bRAF, KIT FLT-3, VEGF-2, VEGFR-3, and PDGFR-ß for sorafitinib) and have also been approved for the therapy of patients with advanced renal cell carcinoma.

Pazopanib was reviewed in a randomized, placebo-controlled, international trial that enrolled 435 patients with clear cell or predominantly clear cell renal cell carcinoma. Nearly half of patients had previously received cytokine treatment while the remainder were therapy naïve. PFS was significantly prolonged in the pazopanib arm at 9.2 months versus 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.

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 previous 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. 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 linked to better quality of life than interferon-alpha.

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

Treatment Options
Because of the lack of curative treatment for metastatic disease and the promise of targeted therapies, patients should be considered for the a number of ongoing clinical trials testing single or combination therapies, including the following:
  • Radical nephrectomy (for T4, M0 lesions).
  • Cytoreductive nephrectomy.
  • Temsirolimus.
  • Sunitinib.
  • Pazopanib.
  • Bevacizumab with or without interferon-alpha.
  • Everolimus (for patients who have previously been treated with sunitinib and/or sorafenib).
  • Sorafenib.
  • Interferon-alpha.
  • IL-2.
  • Palliative EBRT.
  • Clinical trials.
Source: National Cancer Institute, Principles and practice of oncology by Devita.

Cancer terms:
Immune cells: Cells that contribute to immunity by the production of chemical substances or by actual physical contact with the invader are called immune cells. (See immunity). See cancer terms for more cancer related terms.

Medicineworld.org: Renal cell cancer (kidney cancer)

Cancer terms| History of cancer| Imaging techniques| Cancer Main| Bladder cancer news| Cervix cancer news| Colon cancer news| Esophageal cancer news| Gastric cancer news| Health news| Lung cancer news| Breast cancer news| Ovarian cancer news| Cancer news| Pancreatic cancer news| Prostate cancer news| Endometrial cancer news| General info| What is cancer?| Cancer causes| Is cancer hereditary?| Types of cancer| Cancer statistics| Breast cancer main| Breast cancer symptoms| Colon cancer main| Anal cancer| Bladder cancer main| Lung cancer general| Lung cancer main| Non small cell| Small cell| Ovarian cancer main| Treatment of ovarian cancer| Prostate cancer main| Updates in oncology|

Copyright statement
The contents of this web page are protected. Legal action may follow for reproduction of materials without permission.