Renal cell cancer (kidney 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 renal cell cancer Almost all of these patients are incurable. 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. Hence, nephrectomy, in the hope that it will be followed by spontaneous regression of metastases, is not advised. Spontaneous regressions occasionally occur; indeed, a prospective surveillance series of 73 patients with advanced renal cell cancer demonstrated apparent temporary objective regression in 5 (7%) patients without nephrectomy or any therapy. 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. Responses to cytotoxic chemotherapy generally do not exceed 10% for any regimen that has been studied in adequate numbers of patients. Because of early reports of success, progestational agents have been administered to patients with metastatic renal cell cancer, but the frequency of response is disappointingly low, and there is no rationale for their use as anticancer therapy. They may offer subjective palliation, however. Various biologic therapies have been evaluated. Interferon alfas have approximately a 15% objective response rate in appropriately selected individuals. In general, these patients have nonbulky pulmonary and/or soft tissue metastases with excellent performance status (ECOG 0,1) and no weight loss. The interferon alfa doses used in studies reporting good response rates have been in an intermediate range of 6-20 MU - TIW. These responses are rarely complete or durable. More promising are treatments using interleukin-2 (IL-2).Administration of IL-2 appears to have a similar overall response rate to interferon alfa but with approximately 5% of the appropriately selected patients having durable complete remissions. Combinations of IL-2 and interferon have been studied but have not been shown to be better than high-dose IL-2 alone. 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. Outpatient, subcutaneous administration has also demonstrated responses with acceptable toxic effects. Because of the overall poor results with drug treatment, patients with metastatic renal cell cancer should be considered for clinical trials, especially phase I and II trials evaluating newer chemotherapeutic agents, biologics such as interferons or IL-2, and strategies to modulate multidrug-resistant phenotype, which is highly expressed in renal cell cancers. IL-2 Interferon alfa External-beam radiation therapy (palliative). Palliative nephrectomy Radical nephrectomy (for T4 lesions). Surgical excision of metastatic disease with radical nephrectomy (for selected M1 patients). Clinical trials. Treatment of 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. The question and selection of further treatment depends on many factors, including prior treatment, site of recurrence, and so on, 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 primary therapy. Responses to cytotoxic chemotherapy generally do not exceed 10% for any regimen that has been studied in adequate numbers of patients. Because of early reports of success, progestational agents have been administered to patients with metastatic renal cell cancer, but the frequency of response is disappointingly low, and there is no rationale for their use as anticancer therapy. They may offer subjective palliation, however. Various biologic therapies have been evaluated. Interferon alfas have approximately a 15% objective response rate in appropriately selected individuals. In general, these patients have nonbulky pulmonary and/or soft tissue metastases with excellent performance status (ECOG 0,1) and no weight loss. The interferon alfa doses used in studies reporting good response rates have been in an intermediate range of 6-20 MU daily - TIW. These responses are rarely complete or durable. More promising are treatments using interleukin-2 (IL-2). Administration of IL-2, with or without lymphokine-activated killer lymphocytes, appears to have a similar overall response rate to interferon alfa but with approximately 5% of the appropriately selected patients having durable complete remissions. Combinations of IL-2 and interferon have been studied but have not been shown to be better than high-dose IL-2 alone. Low-dose inpatient regimens can retain efficacy with fewer toxic effects, especially hypotension. Outpatient, subcutaneous administration has also demonstrated responses with acceptable toxic effects. Because of the overall poor results with drug treatment, patients with metastatic renal cell cancer should be considered for clinical trials, especially phase I and II trials evaluating newer chemotherapeutic agents, biologics such as interferons or IL-2, and nonmyeloablative allogeneic stem cell transplantation. Treatment options include: IL-2 Interferon alfa External-beam radiation therapy (palliative). Vinblastine. Source: National Cancer Institute, Principles and practice of oncology by Devita.