Approximately 550 to 600 children are diagnosed with Wilms tumor in North America every year. It is more common in children of European and African descent than in Asian children. Girls are slightly more at risk of developing Wilms tumor than boys.

The average age at diagnosis is between 3 and 4 years when the disease is unilateral (affecting only one kidney), but it is generally diagnosed at a younger age when the disease is bilateral (affecting both kidneys). Seventy-five to 80 percent of children with Wilms tumor are diagnosed before the age of 5. Five percent of children with Wilms tumor have tumors in both kidneys at diagnosis.

Genetic factors associated with Wilms tumor

Wilms tumor is believed to result from mutations in certain genes. These genes are associated not only with Wilms tumor, but with several other rare conditions. Roughly 10 percent of children diagnosed with Wilms tumor also have one of the following birth defects or syndromes:

•  WAGR syndrome. WAGR is an acronym for Wilms tumor, aniridia (incomplete formation of the iris of the eye), genitourinary tract abnormalities, and mental retardation. A child with this syndrome, caused by a deletion of the short arm of chromosome 11 (called 11p), has a greater than 30 percent chance of developing Wilms tumor. Aniridia is caused by alterations of a gene called PAX6, which sits on chromosome 11p adjacent to a gene called the Wilms tumor suppressor gene (WT1). WT1 is responsible for formation of the genitourinary system and is implicated in Wilms tumor development. If a child has a deletion of 11p that includes both PAX6 and WT1, there is an increased risk of Wilms tumor. If the deletion affects only PAX6, the risk of Wilms tumor is much lower.

•  Denys-Drash syndrome. This syndrome is characterized by abnormal kidney function and genital abnormalities. It is also associated with mutations of WT1 on chromosome 11p.

•  Beckwith-Wiedemann syndrome. This congenital disorder is characterized by larger-than-normal internal organs, a large tongue, hemihypertrophy (one side of the body grows larger than the other), and hernia of the navel at birth. Sometimes hemihypertrophy can be seen in the absence of the other features of Beckwith-Wiedemann syndrome. Approximately 5 to 10 percent of children with Beckwith-Wiedemann syndrome or hemihypertrophy develop Wilms tumor or other childhood cancers.

•  Nephroblastomatosis. The presence of small pockets of embryonal kidney tissue called nephrogenic rests in the kidney is called nephroblastomatosis. This precancerous condition is usually found in both kidneys. Nephrogenic rests can shrink and disappear, or multiply and develop into Wilms tumor. The condition should be closely monitored and may be treated with chemotherapy.

•  Hereditary Wilms tumor. Inherited Wilms tumor, characterized by tumors in both kidneys and a family history of the disease, is uncommon. Only about 2 percent of all children diagnosed have a family history of Wilms tumor.

Wilms tumor has also been reported in association with other syndromes, such as Perlman syndrome, Simpson-Golabi-Behmel syndrome, Sotos syndrome, mosaic variegated aneuploidy, Fanconi anemia, DICER1 predisposition syndrome, and Bloom syndrome.

Environmental factors

No link has been found between development of Wilms tumor and any environmental factors.

Diagnosis of Wilms tumor

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. Then, the child usually has an abdominal ultrasound and/or a contrast-enhanced computerized tomography (CT) scan. Because some children have tumors in both kidneys, both kidneys need to be examined. A complete blood count (CBC) is ordered, as well as urinalysis to check for signs of blood in the urine. The child will receive blood chemistry tests to evaluate kidney function.

Staging Wilms tumor

Once Wilms tumor has been diagnosed, more tests are done to determine whether the cancer has spread to other parts of the body. This process is called staging and it helps the doctor choose the best treatment for the child. Computerized tomography (CT) scans of the chest should be ordered because approximately 20 percent of children with Wilms tumor have lung metastases at diagnosis.

These are the stages of Wilms tumor:

•  Stage I (approximately 20%). The tumor is limited to the kidney and can be completely removed surgically. No tumor cells are found in the lymph nodes.

•  Stage II (approximately 22%). The tumor extends beyond the kidney, but is completely removed surgically.

•  Stage III (approximately 32%). The tumor is not completely removed surgically or is ruptured during surgery, or disease is found in one or more abdominal lymph nodes.

•  Stage IV (approximately 20%). The disease has spread to the lung, liver, bone, or brain, as well as distant lymph nodes.

•  Stage V (approximately 6%). The tumor is found in 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 therapy, 90 percent of children with Wilms tumor who receive standard 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, a pathologist examines the cancer cells under a microscope. If the nuclei of some of the cells appear larger than normal or irregular in shape, it is called anaplasia. If anaplasia is scattered throughout the tumor, it is called diffuse anaplasia and that means a poorer prognosis. If anaplasia is found in only one area of the tumor (called focal anaplasia) the prognosis is intermediate—between diffuse anaplasia and no anaplasia.

Tumor cells that are not anaplastic are said to be Wilms tumor of favorable histology. The vast majority of children diagnosed with Wilms, approximately 90 percent, have tumor cells with a favorable histology.

The pediatric oncologist will determine the prognosis using many criteria, including stage of disease and presence of anaplasia in the tumor cells. These factors affect the intensity of treatment needed.

Treatment of Wilms tumor

At diagnosis, many parents do not know how to find experienced doctors and the best treatments for their child. State-of-the-art care is available from physicians who participate in the Children’s Oncology Group (COG). This study group includes pediatric surgeons and oncologists, radiation oncologists, researchers, and nurses. COG conducts studies to discover better therapies and supportive care for children with cancer. You can learn more about COG and find a list of its member treatment centers at www.childrensoncologygroup.org.

After diagnosis and staging, your child’s pediatric oncologist will propose the standard treatment or a clinical trial (see Chapter 9, Choosing a Treatment) based on many factors, including your child’s stage of disease and the histology of the tumor. Following is a discussion of treatment for tumors in only one kidney.

Surgery

A pediatric surgeon with experience operating on children with kidney cancer should do all biopsies and surgeries. In North America, children diagnosed with Wilms tumor usually have surgery to remove the kidney, called a nephrectomy, before any other therapy is given (see Chapter 14, Surgery). Occasionally, if the diagnosis is uncertain, a biopsy is performed prior to nephrectomy. Only children with Wilms tumor in both kidneys (bilateral Wilms tumor) or inoperable tumors receive chemotherapy prior to surgery.

Two types of nephrectomies are used to remove Wilms tumor:

•  Radical nephrectomy. Removal of the tumor, as well as the entire kidney and surrounding tissues, including part of the ureter. The remaining kidney is able to compensate for the loss of the other kidney.

•  Partial nephrectomy. Removal of the tumor and a portion of the affected kidney. This type of surgery is usually done for bilateral Wilms tumor or if the other kidney is damaged or has already been removed.

During surgery, the pediatric surgeon takes samples from lymph nodes in the area. The surgeon may also biopsy other areas in the abdomen or the liver if she suspects the cancer might have spread.

Chemotherapy

The vast majority of children diagnosed with Wilms tumor receive chemotherapy (drugs that kill cancer cells) as part of the standard treatment. Several chemotherapy drugs are effective against this type of cancer. The use of dactinomycin and vincristine has dramatically increased survival rates. Children with stage I or stage II disease with favorable histology usually are treated with just these two drugs. Children who are diagnosed with Wilms tumor at a more advanced stage also receive doxorubicin. Children with diffuse anaplasia are treated with doxorubicin, etoposide, cyclophosphamide, vincristine, and sometimes other drugs such as irinotecan and carboplatin. For information about these drugs, see Chapter 15, Chemotherapy.

Children with stage I and stage II disease with a favorable histology are treated for 18 weeks. Children whose tumor has anaplasia and/or a higher stage are treated for 24 weeks. Infants younger than 12 months are given 50 percent of the chemotherapy given to older children to reduce possible long-term effects.

Because chemotherapy can damage healthy, normal cells, the pediatric oncologist may need to adjust the doses. The goal is to minimize potential side effects (see Chapter 16, Common Side Effects of Treatment), while providing adequate treatment for the disease.

Radiation therapy

The decision to use radiation therapy to treat a child with Wilms tumor 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 (see Chapter 17, Radiation Therapy). 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 that will be radiated. Usually, 1,050 centigrays (cGy) is the recommended dose of radiation used in children with advanced stage disease or tumors with unfavorable histology. Children with stage IV disease also receive radiation to treat metastases in the lungs and elsewhere.

Treatment for bilateral tumors

Tumors in both kidneys are found in approximately 5 percent of children diagnosed with Wilms tumor. CT scans and ultrasound usually identify tumors in both kidneys, and at some treatment centers 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans are used to highlight active disease in the main tumor and metastases.

The goal of treatment for stage V Wilms tumor is to try to destroy the tumors while preserving as much healthy kidney tissue as possible. Current treatments use chemotherapy (vincristine, dactinomycin, and doxorubicin) to reduce the size of the tumors before surgery. After 6 weeks of treatment, the kidneys are re-evaluated to see whether the tumors have shrunk sufficiently to allow surgery that leaves part of the kidney in place. If not, chemotherapy continues until week 12, when surgery is performed. After surgery, the chemotherapy regimen may be adjusted based on the tumor histology. Radiation therapy may be used, depending on the tumor’s histology and extent of spread.

Follow up

After treatment, there is a chance that the Wilms tumor will return (called a relapse or recurrence). The likelihood of relapse depends on the initial stage and histology, but the average relapse rate is only 10 percent. Tumor relapse most commonly occurs in the lungs, the original tumor site, or the liver. In 1 to 3 percent of children, a second tumor develops later in the remaining kidney—most of these children were younger than 12 months old when they were originally diagnosed and/or their kidney tumor contained pockets of embryonal tissue called nephrogenic rests. To detect relapse or second tumors, chest x-rays and abdominal ultrasound tests are recommended on the following schedule:

•  Both tests should be performed every 3 months for first 2 years after completion of therapy, followed by every 6 months for the second 2 years, followed by every 12 months for 1 additional year.

•  For children with nephrogenic rests, abdominal ultrasounds should be performed every 3 months until age 7 or 8.