Childhood Wilms Tumor Wilms tumor, also called nephroblastoma, is a cancer that originates in the kidney. The disease gets its name from a German doctor, Max Wilms, who wrote one of the first medical articles about it in 1899. Ninety percent of all kidney cancers in children are Wilms tumor. The remaining ten percent are rare forms of childhood kidney cancers: clear cell sarcoma of the kidney, malignant rhabdoid tumor of the kidney, and occasionally renal cell carcinoma. The kidneys The kidneys, located near the middle of the back, are responsible for filtering the blood and removing harmful waste products. These two bean-shaped organs are each about the size of a fist. The kidney operates as a recycling depot complete with high-tech sanitation engineers. Its main job is to filter harmful waste products from the blood and to regulate the return of reusable chemicals--sodium, phosphorus, and potassium--back to the body. Inside each kidney are millions of microscopic structures that filter out large particles, such as white and red blood cells, as well as most proteins, allowing them to return to the bloodstream. What remains in the kidney after this process is called urine. The urine flows from the kidney through a long tube (ureter) into the bladder, where it is stored until it is eliminated from the body by urination. Who gets Wilms tumor? Wilms tumor is the second most common type of all childhood solid tumors, not including brain tumors. It accounts for approximately 6 percent of all childhood cancers. The average age at diagnosis is between two and three years when the disease is unilateral (affecting only one kidney), but it is generally diagnosed at a younger age in children when the disease is bilateral (affecting both kidneys). Seventy-five to eighty percent are diagnosed before the age of five. Approximately 450 new cases are seen annually in North America. There is a higher incidence in black children than in white children. Conversely, there is a lower incidence among Asian compared to white children. Girls are slightly more at risk of developing Wilms tumor than boys. Genetic factors Wilms tumor is believed to result from mutations or changes in certain genes. The involved genes and other genes located nearby are associated not only with Wilms tumor but several other rare conditions. Approximately 15 percent of children diagnosed with this cancer also have one of the following birth defects or syndromes: Aniridia. A rare condition in which there is incomplete formation of the iris of the eye. It is a congenital defect that can cause blindness. Because of its association with Wilms tumor, children with this rare syndrome should be screened periodically for Wilms tumor. There is no specific genetic testing available for aniridia. WAGR syndrome. A rare genetic condition associated with Wilms tumor. WAGR is an abbreviation for Wilms tumor, aniridia, genitourinary tract abnormalities, and mental retardation. A child with this syndrome has a greater than 30 percent chance of developing Wilms tumor. Beckwith-Wiedemann syndrome. A congenital disorder characterized by larger-than-normal internal organs and hypoglycemia at birth. Hemihypertrophy. A condition in which one side of the body may grow larger than the other. Because of its association with Wilms tumor, children with this syndrome should be screened periodically for the disease. Denys-Drash syndrome. Characterized by abnormal kidney function and genital abnormalities called pseudohermaphroditism (a condition in which genitalia are ambiguous, making it difficult to determine if the child is male or female). This syndrome occurs mostly in boys. Nephroblastomatosis. The presence of small pockets of embryonal kidney tissue under the capsule of the kidney that is usually bilateral. If present, there is a high risk of developing a tumor in the kidney and ultrasound is usually recommended for up to ten years. Hereditary Wilms tumor. Characterized by tumors in both kidneys and a family history of the disease. It is uncommon; 4 to 5 percent of all patients diagnosed have bilateral tumors and 1 to 2 percent have a family history of Wilms. Environmental factors There has been no consistent link between development of Wilms tumor and any environmental factors. Signs and symptoms Wilms tumor is often a difficult disease to diagnose. Usually, a parent notices a lump or mass in the abdominal area while dressing or bathing a child who has no other symptoms. By this time, the tumor is generally very large. Sometimes the tumor is found during routine visits when the pediatrician palpates the toddler's abdomen. Wilms tumor is occasionally diagnosed when the child is evaluated for other unrelated reasons, such as accidental trauma to the abdominal area. This child's cancer didn't produce symptoms before developing into a fairly large tumor: We thought she had the flu. After she had been throwing up for a few hours and was too weak to stand on her own, I was holding her up in the bathroom. As she leaned over my hands, I could feel a lump in her abdomen. The doctor knew what it was the second he felt it. We had tests at the local hospital that confirmed the diagnosis of Wilms tumor. Some children with Wilms tumor have abdominal pain and up to 25 percent will have hematuria (blood in the urine). Blood may be visible to the naked eye or it may only be seen with microscopic evaluations. In addition, up to 25 percent of children have high blood pressure at diagnosis. Other symptoms that may be present include fever, diarrhea, weight loss, shortness of breath, urogenital infections, and anemia (low number of red cells). The child may feel generally tired and unwell. Nausea and vomiting are infrequent symptoms of a Wilms tumor. Diagnosis Several tests and procedures are necessary to diagnose Wilms tumor. The doctor will first perform a physical examination and obtain the child's medical history. This is usually followed by an abdominal ultrasound and/or a CT scan. Occasionally, a scan called magnetic resonance imaging (MRI) is done. Because some children with Wilms tumor have bilateral involvement, both kidneys need to be examined. A complete blood count (CBC) is ordered, as well as urinalysis to check for signs of hematuria (blood in the urine). Kidney function tests are also taken. This parent recounts the swift course of a daughter's diagnosis: I have to say that on diagnosis day our pediatrician was wonderful. When I called the doctor's office and told them about the lump that I had found in her abdomen and the vomiting, no one even hinted at what might be wrong. I was simply told to bring her in as soon as possible. The doctor was examining her less than two hours after my call to his office. He didn't tell me initially what he suspected. Later, he told me that he wanted to be sure before he even mentioned the word to me. He sent us to the local hospital where she underwent her first CT scan. The doctor was waiting for us with the news when we returned to his office. X-rays and CT scans of the chest should be ordered to determine if the disease has spread to the lungs. Approximately 10 percent of children with Wilms tumor have lung metastases at diagnosis. A chemical survey of the blood (called blood chemistries) is done to establish baseline kidney function, since one kidney is usually removed as part of the treatment protocol. Chemical surveys also check for liver disease and elevated levels of urates and phosphate. Staging Once Wilms tumor has been diagnosed, surgery and/or more tests are done to determine if the cancer has spread to other parts of the body. This process is called staging, and it helps the doctor choose the most appropriate treatment for the child. Wilms tumor is staged by the following system, devised by the National Wilms Tumor Study Group (NWTSG): Stage I. The tumor is limited to the kidney and is able to be completely removed surgically. Stage II. The tumor extends beyond the kidney but is able to be completely removed surgically. Stage III. The tumor is not able to be completely removed surgically or is spilled at surgery, but disease is still limited to the abdomen. Stage IV. The disease has spread from the abdomen through the bloodstream and may be found in the lung, liver, bone, or brain as well as distant lymph nodes. Stage V. The tumor is found on both kidneys at the time of diagnosis. Prognosis Treatment of Wilms tumor in children is one of medicine's success stories. Due to improvements in surgical techniques, drug therapies, and radiation, 85 to 90 percent of children with Wilms tumor who receive state-of-the-art treatment are cured. The best treatment for each child with Wilms is determined by analysis of several clinical and biologic features. After a biopsy or surgery, the pathologist examines the nucleus of the cancerous cells under a microscope. If the nuclei of some of the cells appear larger than normal or irregular in shape, it is called anaplasia. Local anaplasia does not appear to affect prognosis. If there is a large proportion of anasplasia scattered throughout the tumor, it is called diffuse anasplasia and has a poorer prognosis. Tumor cells that are not anaplastic are said to be Wilms tumor of favorable histology. The vast majority, approximately 95 percent, of children diagnosed with Wilms have cells with a favorable histology. The oncologist will determine the prognosis using many criteria, including stage of disease, histology of the tumor cells, age of the child, and size of the tumor. These factors affect the aggressiveness of treatment needed. For example, a child diagnosed with stage II, favorable histology, receives less intensive therapy than does a child with stage IV, unfavorable histology. Treatment The vast majority of children with Wilms who receive optimal treatment are cured of the disease. At diagnosis, many parents are confused about how to find the best doctors and treatments for their child. State-of-the-art care is available from physicians who participate in the National Wilms Tumor Study Group, the Children's Cancer Group (CCG), and the Pediatric Oncology Group (POG). These study groups, composed of pediatric surgeons and oncologists, urologists, radiation oncologists, researchers, and nurses, establish the standard of care for patients worldwide, conduct new studies to discover better therapies or fine tune old ones, and establish follow-up for survivors. They are in the process of merging into one entity called the Children's Oncology Group (COG). If the treatment center you are referred to is a member of one of these groups, you can rest assured that your child will have access to the best thinking on the treatment of pediatric cancers. The doctor will choose the best treatment or clinical trial based on many factors, including your child's age, stage of disease, and size and histology of the tumor. For most patients, treatment is surgery followed by chemotherapy. Some children also require radiation. Surgery Children diagnosed with Wilms tumor usually have a surgical procedure, called a nephrectomy, performed before any other therapy is initiated. Occasionally, if the diagnosis is questionable, a biopsy will be performed prior to nephrectomy. In North America, only children with bilateral Wilms tumor receive chemotherapy prior to surgery. There are three different types of nephrectomies: Simple nephrectomy. Removal of the tumor as well as the entire kidney and ureter. The remaining kidney is able to compensate for the loss. Partial nephrectomy. Removal of the tumor and a portion of the affected kidney. It is done usually if the other kidney has already been removed or is damaged. Radical nephrectomy. Removal of the tumor, kidney, and some surrounding tissue. During surgery, the surgeon evaluates the remaining kidney for disease and takes samples from lymph nodes in the area. The surgeon may also biopsy areas of the liver if she suspects that disease may be present. It is not always possible to predict how long the surgery will take, as this parent remembers: I was told that the surgery would take between two and three hours. It was just over four hours, which drove me insane in the waiting room. I hadn't been told anything about what Elizabeth would look like after the surgery. My cousin is a surgical nurse at a nearby hospital. She stopped by during my wait and prepared me. If she hadn't told me what to expect, I think I would have broken down from the shock. I wasn't prepared for all of the tubes and wires and the puffy face and anesthesia reactions. And no one told me about the central line. I had to ask one of the nurses after the fact what it was. Elizabeth was expected to be out of bed and moving around on the second day. By the end of day three she was beginning to move around more like her old self, and by day four there was no slowing her down. Chemotherapy All children diagnosed with Wilms tumor receive chemotherapy (drugs that kill cancer cells) as part of their treatment protocol. There are several chemotherapy drugs that are effective against this type of cancer. The use of dactinomycin and vincristine has dramatically increased survival rates. Children with early-stage disease often are treated with just these two drugs. For those who are diagnosed at more advanced stages, doxorubicin, cyclophosphamide, etoposide, ifosfamide, and carboplatin may be added. Most children with Wilms tumor enter a clinical trial tailored to the stage and histology of their disease. The clinical trial protocol outlines the chemotherapy drugs and dosages that are used. Since chemotherapy can damage healthy, normal cells, the oncologist may need to adjust the actual dose that is administered. The goal is to minimize potential side effects while providing adequate treatment for the disease. This little girl's discomfort was well controlled: My daughter's main side effects from the dactinomycin and vincristine were constipation and nausea. She was given a standard dose of Senecot every day for the constipation, and we were given a standing prescription for Zofran to control the nausea. Both of these drugs worked wonders for her. She really suffered very little discomfort during chemotherapy. Radiation The decision to use radiation therapy to treat a child with Wilms is based largely on the stage and histology of the tumor. Children with stage I and stage II favorable histology disease do not require radiation. For children with more advanced stages of disease, external beam radiation therapy is given. This type of treatment uses high-energy rays, delivered from outside the body, to kill cancer cells. The amount of disease present will determine the size of the area to be radiated. Usually, 1000 cGy, with an optional 1000 cGy boost to the tumor, is the recommended dose of radiation given to children with advanced-stage diseases or tumors with unfavorable histology. Side effects from this child's radiation therapy were mild: My one-year-old son had a huge tumor that went from his diaphragm to his bladder and crossed the midline. He had a simulation that lasted one and a half hours, then radiation to the spinal cord and abdomen, once a day for five days. He tolerated it very well. The only side effect he had was red peeling skin. He did have doxorubicin for the following six months and had radiation recall several times. His peeling skin would return for a couple of days, then disappear. Newest treatment options To learn about the newest treatments available, call (800) 4-CANCER and ask for the PDQ (physicians data query) for Wilms tumor. These free statements, also available on the Internet at http://cancernet.nci.nih.gov/, explain the disease, state-of-the-art treatments, and ongoing clinical trials. There are two versions available: one for patients, which uses simple language and contains no statistics, and one for professionals, which is technical, thorough, and includes citations to scientific literature. As this survivor of Wilms tumor describes it, her cancer early so in life has not harmed her quality of life: I had Wilms tumor in 1962 when I was two years old. I had one kidney removed, then radiation and chemotherapy. I recovered and had a perfectly normal childhood. Other than not wearing bikinis because of the big scar right around my waist, it didn't affect me much. I played hockey, basketball, and other contact sports without problems. I have no late effects from the treatment other than slight curvature of the spine and a few less pockets of fat on the side they irradiated. They told me that one of my fallopian tubes was damaged, but I have had three sons, all over seven pounds. My childhood cancer experiences created a deep fascination with medicine, and I am now a nurse. This fact sheet was adapted from Childhood Cancer: A Parent's Guide to Solid Tumor Cancers, by Honna Janes-Hodder and Nancy Keene, © 2001 by Patient-Centered Guides. For more information, call (800) 998-9938 or see www.patientcenters.com.