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
Matthew was 1 year old when he was diagnosed with Wilms tumor. Everyone used to tell me how lucky I was because he was so young and he probably wouldn’t remember anything. Funny, because lucky was not a word I would use to describe the scenario.
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.
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
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 2 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 pediatrician was waiting for us with the news when we returned to his office.
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.
Elizabeth’s cancer was found by CT scan. That probably gave the doctors up front a good indication of what they were facing (how large the tumor is, how far it has spread). They said that she had a cancerous tumor called Wilms, and we were sent to the children’s hospital. Surgery was immediately scheduled. I was told that what happened following the surgery would depend on what they found in surgery. I was also told at the very beginning that she would lose her kidney. If they discovered that the cancer had progressed beyond the kidney (e.g., to the lung), it was possible that further surgery would be done. Following the surgery, tissues were typed and staged. A few days after the surgery, the doctors and I sat down in the conference room. It was then that I was given the staging information and the list of all of the stages so that I could see how we fit into the big scheme of things.
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.
We sat and waited for hours and then the door clicked and white coats entered the room. The doctors sat on the couch and gave us the diagnosis. They explained it was bilateral Wilms tumor, a pediatric kidney cancer that was quite common, but being on both kidneys made it unusual. I asked what stage it was and when they said “Stage V” I just lost it. Tala was 14 pounds, how could she survive this? I don’t remember what they were saying after that, I just remember it was very dark in the room. They explained that they would do 6 weeks of chemotherapy to try and destroy the tumors in her chest and they said we would start chemo the next day.
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.
The initial pathology was Stage 1, favorable histology with no lymph node involvement, and we left hoping and praying we were done. We were told we’d get a call from oncology on Monday or Tuesday. A senior pathologist reviewed the slides and he felt one of the lymph nodes had involvement, which took Victoria from stage 1 to stage 3. They sent the tissue on to a third party to evaluate, so they wouldn’t over treat or under treat her. We waited another week for that to come back, and they agreed that the one lymph node was likely involved. So the same day that we got that confirmation, we took her to the hospital for chemotherapy. We were on a research study that required her to start chemo within 2 weeks of surgery.
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.
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.
We walked Brinley (age 3) down to surgery at 7:45 in the morning. We loved that we were able to stay with her until the moment she closed her eyes. The next time we got to see her was 5:30 that night when she went into recovery. It was a long day. She was groggy and in some pain. My sister-in-law saw her and burst into tears, but we were happy because we had talked to the doctor and knew he thought she was doing very well. It’s funny how two people can see the same thing in a completely different way.
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.
We had an awesome surgical team. Victoria went in for surgery at 1 in the afternoon and we didn’t get back to her until 7. They had told us that it would take 3 to 7 hours. They texted us status updates on a pager during the surgery and let us know where to meet her for recovery. She had an epidural when she came out of surgery, so that is how they managed her pain until the next day. They placed her port while she was in surgery. They removed and examined over 22 lymph nodes from her abdomen. We stayed at the hospital until Saturday.
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.
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.
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
My 1-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 5 days. He tolerated it very well. The only side effect he had was red peeling skin. He did have doxorubicin for the following 6 months, and had radiation recall several times. His peeling skin would return for a couple of days, then disappear.
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.
The doctor sat us down to tell us the initial plan for my daughter’s treatment: 6 weeks of chemotherapy, which they hoped would shrink the kidney tumors enough to do surgery; if not, they would add 6 more weeks of chemo and then do the surgery. The goal was to save as much of each kidney as they could. She was given vincristine, dactinomycin, and doxorubicin. We stayed in the hospital just short of 3 weeks because her counts were low and because she was on intravenous feedings. We had a lot to learn to be able to take her home. After the surgery, her last 19 weeks of chemo were done as an outpatient in the day treatment facility.
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.
Table of ContentsAll Guides
- 1. Diagnosis
- 2. Bone Sarcomas
- 3. Liver Cancers
- 4. Neuroblastoma
- 5. Retinoblastoma
- 6. Soft Tissue Sarcomas
- 7. Kidney Tumors
- 8. Telling Your Child and Others
- 9. Choosing a Treatment
- 10. Coping with Procedures
- 11. Forming a Partnership with the Medical Team
- 12. Hospitalization
- 13. Venous Catheters
- 14. Surgery
- 15. Chemotherapy
- 16. Common Side Effects of Treatment
- 17. Radiation Therapy
- 18. Stem Cell Transplantation
- 19. Siblings
- 20. Family and Friends
- 21. Communication and Behavior
- 22. School
- 23. Sources of Support
- 24. Nutrition
- 25. Medical and Financial Record-keeping
- 26. End of Treatment and Beyond
- 27. Recurrence
- 28. Death and Bereavement
- Appendix A. Blood Tests and What They Mean
- Appendix B. Resource Organizations
- Appendix C. Books, Websites, and Support Groups