All About Wilms Tumor

What is a Wilms tumor?

Wilms tumor (WT) is a cancer that starts in the kidneys. The kidneys are two bean-shaped organs found in the back of the belly, right in front of where the lowest ribs can be felt on the back. Wilms tumor, also called nephroblastoma, is the most common kidney cancer in children. It can affect just one kidney (unilateral) but can affect both (bilateral). There can also be more than one tumor in the same kidney (multicentric). The two main types of WT are favorable histology (FH), and the less common, unfavorable or anaplastic histology (UH). This is determined by the amount of anaplastic histology (cell changes seen with a microscope) that is present in the tumor.

What causes a Wilms tumor and who is at risk?

Each year about 500 new cases are diagnosed in the United States. Both boys and girls can be affected but girls are slightly at higher risk. The average age of diagnosis is 3-4 years old and it is more common in African Americans.

In normal human development, each person has an entire set of paired chromosomes. One half of the pair is from the mother and the other half is from the father. Each chromosome is further divided into smaller sections called genes, which hold a person's unique DNA, or "genetic code.” This code is used to build very important proteins in the body. Wilms is thought to happen when there is an accidental loss of certain parts of DNA, known as tumor suppressor genes. These genes regulate cell growth. When these suppressor genes are lost, too many cancer cells grow. This results in a cancer (tumor) in the kidney. There have been several tumor suppressor genes that have been linked to Wilms tumor, such as WT1, WT2, and P53, among others.

The accidental loss of this DNA or gene that leads to WT happens early during development, usually before birth. A majority of the cases are "sporadic,” meaning that WT does not "run in the family.” It is not clear exactly what causes these genes to be deleted and there are no known causes of WT (like anything that a child or mother could have been exposed to). Because each person has 2 copies of each gene, both copies of a tumor suppressor gene have to be missing to develop WT. If only one copy of the gene is missing, a person is a carrier of the mutation, but may not always have the disease.

Only about 1% of WTs are "familial" or run in the family. In these patients, either the mother or the father carries a gene deletion, which is passed on to the child. The child is born with only one copy of the gene, and if that one gene is somehow deleted, he or she will develop WT.

About 10% of WT cases are linked with other medical problems. Together, these medical problems are called a syndrome. Some syndromes include:

• WAGR syndrome:
  • Wilms tumor.
  • Aniridia (eyes without the irises, or colored parts).
  • Genitourinary malformations (such as genital or kidney deformities).
  • Mental Retardation.
  • There is about a 30% chance of developing WT in people with WAGR syndrome.

• Beckwith-Wiedemann syndrome: marked by an abnormally large body size and overgrown abdominal (belly) organs.
  • There is about a 6% chance of developing WT in people with Beckwith-Wiedemann syndrome.
• Denys-Drash syndrome: People with Denys-Drash syndrome have kidney disease, ambiguous genitalia, and WT.

How can a Wilms Tumor be prevented in a child?

Children who are diagnosed with a Wilms tumor often do not have any risk factors. Because of this, there is no way to prevent WT.

What screening tests are used?

There are no recommended screening tests for childhood cancer. A child won't be tested for a Wilms tumor unless they are showing signs or symptoms of the disease or one of the syndromes listed above.

What are the signs and symptoms of a Wilms tumor?

Most children with Wilms tumor will have:

• A mass in their belly that is often large enough to be felt.
• The child may or may not have belly pain from pressure, bleeding, or bowel rupture due to the growing mass.

Other possible symptoms include:

• Fever.
• Nausea.
• Not feeling hungry.
• Having a hard time passing a bowel movement.
• Blood in the urine (hematuria),
• Having a hard time breathing.

In some cases, WT is not diagnosed until it has spread (metastasized) to the lungs, which in some cases could cause breathing (respiratory) problems. Any child with WT should also be checked for abnormalities of the genitalia or urinary tract. They should be carefully examined for any of the traits related to the genetic syndromes mentioned above, as WT may be part of a broader syndrome. Routine screening in people with genetic defects known to be associated with WT may be helpful, however, it is not proven.

How is a Wilms tumor diagnosed?

If it is thought that your child has a Wilms tumor, the medical workup starts with a thorough history, including family history and a physical exam. Imaging tests will be ordered, including:

• Abdominal ultrasound is usually the first test ordered to evaluate the kidneys.
• Doppler ultrasound can also be used to evaluate blood flow to the kidneys and whether the tumor has spread into the blood vessels of the kidney.
• Abdominal CT scan is also recommended to determine if there has been any spread to other organs, as well and if there is any disease in the other kidney.
• CXR or CT scan of the chest is used to determine if the disease has spread to the lungs.
• MRI, bone scans, and lab tests may also be ordered.

If your child has surgery to remove the tumor, a biopsy will be done at this time to make a definitive diagnosis. The tumor may also be tested for changes in certain chromosomes. This tells the care team which treatments might work best for your child. Blood and urine tests may also be ordered.

How are Wilms Tumors staged?

Staging determines the extent of the cancer and can help create a treatment plan. The most commonly used staging system for Wilms tumor is the Children’s Oncology Group staging system.

Children’s Oncology Group Staging System

Stage I: The tumor is found in 1 kidney and can be completely removed with surgery.

Stage II: Cancer is found in the kidney and in the fat, soft tissue, or blood vessels near the kidney. It may have spread to the renal sinus. The renal sinus is the part of the kidney where blood and fluid enter and exit the organ. The tumor can be completely removed with surgery.

Stage III: Cancer is found in areas near the kidney and cannot be completely removed with surgery. The tumor may have spread to nearby organs and blood vessels or throughout the abdomen and to nearby lymph nodes. Lymph nodes are tiny, bean-shaped organs that help fight infection. Stage III cancer has not spread outside the abdomen.

Stage IV: Cancer has spread to other more distant organs, such as the lungs, liver, bones, and brain, or to lymph nodes outside the abdomen.

Stage V: Cancer cells are in both kidneys at the same time. The tumor in each kidney is staged separately.

Refractory: A refractory tumor is a tumor that does not shrink during or after treatment.

Recurrent: A recurrent tumor is a tumor that has come back after treatment. The tumor may come back in the area where it first started or in another part of the body. If the tumor does return, there will be another round of tests to learn about the extent of the recurrence. These tests and scans are often similar to those done at the time of the original diagnosis.

Risk Group

Instead of stage, your child’s care team may discuss the risk group, which helps to guide treatment (very low, low, standard, higher, or bilateral). These risk groups are based on the stage of the tumor, the age of your child, the weight of the tumor, the histology of the tumor and some of the genetics of the tumor (Loss of heterozygosity or LOH). Each risk group has its own guideline for treatment, discussed below.

How are Wilms Tumors treated?

This cancer is rare and it is important for treatment to be done at a facility that has experience working with children that have Wilms Tumor. Children with Wilms Tumor will be cared for by a large team of care providers which may include a surgeon, an oncologist and a radiation oncologist. The three types of treatments include surgery, chemotherapy, and radiation.

Your child’s care team will use the information gathered to determine which treatment option is best. Risk group-defined treatments focus on the type, stage, and histology of the tumor. Your child’s treatment plan will take into account possible side effects, you and your family’s preferences, as well as your child’s overall health.

Surgery

The most important role of surgery is to remove the whole tumor without rupturing it. The surgeon looks at the area around the kidney for possible metastasis (spread of the cancer). The surgery of choice is often total removal of the involved kidney (a radical nephrectomy), with a biopsy of specific abdominal (belly) lymph nodes.

Chemotherapy

Chemotherapy is the use of medications to kill cancer cells. Chemotherapy can be given in a number of ways including into a vein, by mouth, into a muscle, or into the cerebrospinal fluid. It is most commonly given into a vein (intravenous or IV). Chemotherapy is often used because it can reach almost any cell in the body. Because of this, it is called a systemic (goes through the whole body) therapy.

Patients with very large or extensive tumors may have chemotherapy before surgery. This is called “preoperative chemotherapy.” Before starting chemotherapy, a biopsy through the abdominal (belly) skin (percutaneously) should be done to make the diagnosis. Preoperative chemotherapy makes tumor removal easier and may lower the chance of surgical complications or problems. Other patients may need chemotherapy after the tumor has been removed. Some patients may just be observed after surgery, without chemotherapy.

The chemotherapy drugs commonly used in WT patients are dactinomycin, carboplatin, irinotecan, vincristine, doxorubicin, etoposide and cyclophosphamide. Not all medicines may be used for everyone. For example, in some early stages of WT, only vincristine and dactinomycin may be used after surgery. Mesna, a medication (not a chemotherapy) used to protect the bladder wall from the harmful effects of cyclophosphamide (a chemotherapy medication) may be used.

Radiation Therapy

Radiation therapy is used to treat areas in the belly when there is concern for Wilms tumor cells being left behind after surgery. Radiation is the use of high energy x-rays to kill cancer cells. Sometimes, this radiation is only given to the area where the kidney was (the “flank”). If there is concern that tumor cells are spread through the belly, radiation may be given to the belly also.

Radiation may also be used to treat metastases (spread) to the lungs, liver, and/or bones.

Proton therapy is a type of radiation that allows the delivery of radiation dose, potentially with decreased exposure of nearby organs and tissues. The role of proton therapy in treatment of Wilms tumor is very limited, and proton therapy is only used on clinical trials for treatment of patients with Wilms tumor.

Clinical Trials

There are clinical research trials for most types of cancer, and every stage of the disease. Clinical trials are designed to determine the value of specific treatments. Trials are often designed to treat a certain stage of cancer, either as the first form of treatment offered, or as an option for treatment after other treatments have failed to work. They can be used to evaluate medications or treatments to prevent cancer, detect it earlier, or help manage side effects. Clinical trials are extremely important in furthering our knowledge of disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service.

Follow-Up Care and Survivorship

After treatment is finished, your child will have a plan for follow up care, based on the initial stage and histology of the tumor. At first, the visits with their care team will be frequent, but as time passes, there will be more and more time in between visits. These visits may include blood tests and imaging scans. Having only one working kidney can raise concerns for damage to or a decrease in the functioning of the kidney. It can also lead to high blood pressure, as the kidney regulates blood pressure. The remaining kidney can also be damaged with treatment. Children treated for WT may be at increased risk for developing second cancers. This risk depends on the intensity of their therapy and certain genetic factors.

It is important to continue to be seen by a primary care provider who has information about the cancer treatment, and can follow your child for any long term concerns along with the oncology team. The oncology team will discuss the plan for follow up.

What can you or your child do to live a healthy life after treatment? There is no supplement or specific food you can eat to assure good health, but there are things you can do to live healthier, prevent other diseases, detect cancers early and work with the social and emotional issues, including insurance, employment, relationships, sexual functioning, and fertility, that a prior cancer diagnosis sometimes brings with it. Your oncology team is there to support you and can help you find support resources.

It is important to have a plan for who will provide follow up care (an oncologist, survivorship doctor or primary care doctor). Talk with the team about developing a survivorship care plan or develop one using the Smart ALACC tool. Your child may benefit from being seen in a survivorship clinic. At a survivorship clinic a provider can review your child's history and provide recommendations. You can contact cancer centers in your area to see if they have a survivor's clinic or search for a clinic on  OncoLink's survivorship clinic list.

Having one functioning kidney can raise concerns for damage to or a decrease in the functioning

Resources for more information

Wilms Tumor– The American Cancer Society

Wilms Tumor– St Jude Children’s Research Hospital