Wilms Tumor - Childhood

General comments about treatment

Overall, about 9 of 10 children with Wilms tumor are cured. A great deal of progress has been made in treating this disease with surgery, radiation therapy, and chemotherapy. Much of this progress in the United States has been because of the work of the National Wilms Tumor Study Group (now part of the Children's Oncology Group), which conducts clinical trials of new treatments for most children with Wilms tumor. Today, most children with this cancer are treated in a clinical trial to try and improve on what doctors believe is the best treatment. The goal of these studies is to find ways to cure as many children as possible while limiting side effects by giving as little treatment as is necessary.

Because Wilms tumors are rare, few doctors outside of those in children's cancer centers have much experience in treating them. Most doctors recommend a team approach that includes the child's pediatrician as well as specialists at a child's cancer center. For Wilms tumors, the doctors on this team often include:

A pediatric surgeon or pediatric urologist (doctor who treats urinary system problems in children [and genital problems in boys])

A pediatric oncologist (doctor who uses chemotherapy and other medicines to treat childhood cancers)

A pediatric radiation oncologist (doctor who uses radiation therapy to treat cancer in children)

Many other specialists may be involved in your child's care as well, including nurse practitioners, nurses, psychologists, social workers, rehabilitation specialists, and other health professionals.

After your child's Wilms tumor is found and its stage and histology are determined, your cancer care team will suggest a treatment plan. Take your time and think about all of your options.

You can often get a second opinion if you have questions about the recommended plan (or if you just want to confirm this is the best option). If you get one, it's important to get it fairly quickly because Wilms tumors are usually very large and tend to grow fast.

The main types of treatment that can be used for Wilms tumor are:

Surgery

Chemotherapy

Radiation therapy

Most children will get more than one type of treatment.

In the United States, surgery is the first treatment for most Wilms tumors. In Europe, doctors prefer to give a short course of chemotherapy before the surgery. There seems to be no difference in the results from these 2 approaches.

If any cancer cells remain after the first operation, radiation therapy or more surgery may be needed. The first goal of treatment is to remove the primary (main) tumor even if the cancer has spread to distant parts of the body. Sometimes the tumor may be hard to remove. It may be very large, it may have spread into nearby blood vessels or other vital structures, or it may be in both kidneys. For these children, doctors might use chemotherapy, radiation therapy, or a combination of the 2 to shrink the tumor(s) before trying surgery.

The next few sections describe the types of treatments used for Wilms tumors. This is followed by a description of the most common approaches used for these tumors based on the tumor stage (extent) and histology (appearance under a microscope).

Surgery for Wilms tumors

Surgery is the main treatment for nearly all children with Wilms tumor. It should be done by a surgeon who specializes in operating on children and has experience in treating these cancers.

Removing the tumor

The main goal of surgery is to remove the Wilms tumor. A major concern during the operation is to try to remove the entire tumor in one piece to prevent the possible spread of cancer cells within the abdomen. Surgeons who operate on these tumors are careful to limit the chance of this type of cancer spread whenever possible. If the surgeon finds (either with imaging tests done before surgery, or upon starting the operation) that the entire tumor can’t be removed safely, other treatments may be used. If these treatments shrink the tumor enough, surgery can then be done more safely.

Depending on the situation, different operations may be used.

Radical nephrectomy: This is the most common operation for Wilms tumor that is only in one kidney, as it provides the best chance of making sure all of the tumor is removed. During this procedure, the surgeon makes an incision (usually down the middle of the abdomen) and removes the cancer along with the whole kidney, the fatty tissue around the kidney, the ureter (tube that carries urine from the kidney to the bladder), and the attached adrenal gland (a hormone-making gland that sits on top of the kidney). Most children can live very well with only one kidney.

Partial nephrectomy (nephron-sparing surgery): In the small number of children who have Wilms tumors in both kidneys, the surgeon will try to save some normal kidney tissue, if possible. The surgeon may remove the kidney containing the most tumor with a radical nephrectomy. In the other kidney the surgeon may do a partial nephrectomy, which removes just the tumor and a margin of normal kidney around it. Another option may be to do partial nephrectomies in both kidneys.

Sometimes, both kidneys may need to be removed completely. The child will then need dialysis several times a week. In this procedure, a machine does the job of the kidneys by filtering waste products out of the blood. Once the child is healthy enough, a kidney transplant may be an option if a donor kidney becomes available.

Assessing the extent of the disease (surgical exploration)

Another main goal of the operation to remove the tumor (radical or partial nephrectomy) is to determine the extent of the cancer and whether or not it can all be removed. Lymph nodes near the kidney will also be removed to look for cancer cells in them. (Lymph nodes are bean-sized collections of immune cells to which cancer often spreads.) Lymph node removal is known as a regional lymphadenectomy.

The other kidney and nearby organs such as the liver may also be looked at closely, and any suspicious areas biopsied (samples taken to be looked at under a microscope).

Knowing if a Wilms tumor has spread to the lymph nodes, the other kidney, or other nearby organs is important in determining its stage and further treatment options.

Placing a central venous access line or device (port)

Often, if the child is going to get chemotherapy, a surgeon will insert a small plastic tube called a catheter into a large blood vessel – usually under the collar bone. This tube may be called a venous access line, venous access device, central venous catheter, or just a port. The end of the tube will be just under the skin or sticking out of the chest area or upper arm. This can be left in place for several months to take blood samples for tests and to give intravenous (IV) chemotherapy drugs and blood transfusions, without needing to puncture the skin in the arm each time. Members of the cancer care team will teach you how to care for your child's venous access device to reduce the risk of problems such as infections.

Possible risks and side effects of surgery

Surgery to remove a Wilms tumor is a serious operation, and surgeons are very careful to try to limit any problems either during or after surgery. Complications during surgery such as bleeding, injuries to major blood vessels or other organs, or reactions to anesthesia are rare, but they can happen.

Almost all children will have some pain for a while after the operation, although this can usually be helped with medicines if needed. Other problems after surgery are uncommon but can include internal bleeding, infections, or problems with food moving through the intestines.

If there are tumors in both kidneys, another concern is the loss of kidney function. In these cases, doctors must balance between making sure the tumors are removed completely and removing only as much tissue as is needed. Children who have all or parts of both kidneys removed may need dialysis, and may eventually need a kidney transplant.

Chemotherapy for Wilms tumors

Chemotherapy (often called chemo) uses anti-cancer drugs that are given into a vein or by mouth (in pill form). These drugs enter the blood and reach all areas of the body, which makes this treatment useful for cancer that has spread or might have spread to organs beyond the kidney.

Most children with Wilms tumors will get chemotherapy at some point during their treatment. In the United States, chemo is usually given after surgery. Sometimes it may be needed before surgery to shrink a tumor to make the operation possible. In Europe, chemo is given before surgery and continued afterward. In both cases, the type and amount of chemotherapy depend on the stage and histology of the cancer.

The chemo drugs used most often to treat Wilms tumor are actinomycin D (dactinomycin) and vincristine. For tumors at more advanced stages, those with unfavorable histology, or tumors that recur after treatment, other drugs such as doxorubicin (Adriamycin), cyclophosphamide, etoposide, irinotecan, and/or carboplatin may also be used.

These drugs are injected into a vein or into a venous access device. Different drugs, doses, and lengths of treatment are used, depending on the type and stage of the Wilms tumor and the child's age. In most cases, the drugs are given once a week for at least several months. They are usually given by a nurse in the doctor's office or in the outpatient section of the hospital. In some cases, children with Wilms tumors stay in the hospital while they are getting chemotherapy, but usually this is not necessary.

Possible side effects of chemotherapy

Chemo drugs attack cells that are dividing quickly, which is why they often work against cancer cells. But other cells in the body, such as those in the bone marrow, the lining of the mouth and intestines, and the hair follicles, also divide quickly. These cells are also likely to be affected by chemotherapy, which can lead to side effects.

The side effects of chemotherapy depend on the type of drugs, the amount taken, and the length of treatment. Possible short-term side effects can include:

Hair loss

Mouth sores

Loss of appetite

Nausea and vomiting

Diarrhea or constipation

Increased chance of infections (from low white blood cell counts)

Easy bruising or bleeding (from low blood platelet counts)

Fatigue (from low red blood cell counts)

Your child's doctor and treating team will watch closely for any side effects that develop. There are often ways to lessen these side effects. For example, drugs can be given to help prevent or reduce nausea and vomiting. Be sure to ask your child's doctor or nurse about medicines to help reduce side effects, and let him or her know if your child has side effects so they can be managed.

Along with the effects listed above, some drugs can have specific side effects. For example:

Vincristine can damage nerves. Some patients may notice weakness, tingling, numbness, or pain, particularly in the hands and feet.

Doxorubicin may cause heart damage. The risk of this happening goes up as the total amount of the drug that is given goes up. Doctors try to reduce this risk as much as possible by not giving more than the recommended doses and by checking the heart with a test called an echocardiogram (an ultrasound of the heart) during treatment.

Cyclophosphamide can damage the bladder, which can cause blood in the urine. The chance of this happening can be lowered by giving the drug with plenty of fluids and with a drug called mesna, which helps protect the bladder.

Lab tests to check for side effects of chemotherapy

Before giving chemotherapy, your child's doctor will check blood test results to check liver, kidney, and bone marrow function. If there are problems, chemotherapy may need to be delayed or the doses reduced.

The complete blood count (CBC) includes counts of white blood cells (WBCs), red blood cells (RBCs), and blood platelets. Chemotherapy can lower the numbers of these blood cells, so blood counts will be watched closely during and after chemotherapy.

Blood chemistry tests measure certain blood chemicals that tell doctors how well the liver and the kidneys are working. Some chemo drugs can damage the kidneys and liver.

Long-term side effects of chemotherapy

Possible long-term effects of treatment are one of the major challenges facing children after cancer treatment.

For example, if your child is given doxorubicin (Adriamycin), there is a chance it could damage his or her heart. Your child's doctor will carefully watch the doses used and will check your child's heart function with imaging tests.

Some chemotherapy drugs can increase the risk of developing a second type of cancer (such as leukemia) years after the Wilms tumor is cured. But this small increase in risk has to be weighed against the importance of chemotherapy in treating Wilms tumor.

Radiation therapy for Wilms tumor

Radiation therapy uses high-energy rays or particles to kill cancer cells. Radiation therapy is usually part of treatment only for more advanced Wilms tumors (stages III, IV, and V) and for some earlier stage tumors with unfavorable histology.

The type of radiation used for Wilms tumors, known as external beam radiation therapy, focuses radiation from outside the body on the cancer. It is much like getting an x-ray, although the dose of radiation is much higher. The total dose of radiation is divided into daily fractions, usually given over a couple of weeks.

Before treatments start, the radiation team takes careful measurements with imaging tests such as CT or MRI scans to determine the correct angles for aiming the radiation beams and the proper dose of radiation.

For each treatment session, your child lies on a special table while a machine delivers the radiation from a precise angle. Your child may be fitted with a plastic mold resembling a body cast to keep him or her in the same position each time so that the radiation can be aimed more accurately. Each session lasts about 15 to 30 minutes, with most of the time being spent making sure the radiation is aimed correctly. The actual treatment time each day is much shorter. The treatment is not painful, but some younger children may be given medicine to make them drowsy before each treatment to help make sure they stay still.

Some newer radiation techniques allow doctors to focus the radiation more precisely.

Three-dimensional conformal radiation therapy (3D-CRT)

3D-CRT uses the results of imaging tests such as MRI and special computers to precisely map the location of the tumor. Several radiation beams are then shaped and aimed at the tumor from different directions. Each beam alone is fairly weak, which makes it less likely to damage normal body tissues, but the beams converge at the tumor to give a higher dose of radiation there.

Intensity modulated radiation therapy (IMRT)

IMRT is an advanced form of 3D therapy. In addition to shaping the beams and aiming them at the tumor from several angles, the intensity (strength) of the beams can be adjusted to limit the dose reaching the nearby normal tissues. This may allow the doctor to deliver a higher dose to the tumor. Many major hospitals and cancer centers now use IMRT.

Possible side effects of radiation therapy

Radiation is often an important part of treatment, but young children’s bodies are very sensitive to it, so doctors try to use as little radiation as possible to help avoid or limit any problems. Radiation therapy can cause both short-term and long-term side effects. Side effects depend on the dose of radiation and where it is aimed.

Possible short-term effects:

Effects on skin areas that receive radiation can range from mild sunburn-like changes and hair loss to more severe skin reactions.

Radiation to the abdomen (belly) can cause nausea or diarrhea.

Radiation therapy can make a child tired, especially toward the end of treatment.

Possible long-term effects:

Radiation therapy can slow the growth of normal body tissues (such as bones) that get radiation, especially in younger children. In the past this led to problems such as short bones or a curving of the spine, but this is less likely with the lower doses of radiation used today.

Radiation that reaches the chest area can affect the heart and lungs. This does not usually cause problems right away, but in some children it may eventually lead to heart or lung problems as they get older.

Radiation to the abdomen in girls may damage the ovaries. This might lead to abnormal menstrual cycles or problems getting pregnant or having children later on.

Radiation can damage DNA. As a result, radiation therapy slightly increases the risk of developing a second cancer in the areas that get radiation, usually many years after the radiation is given. This doesn't happen often with Wilms tumor because the amount of radiation used is low.

Parents should continue to have their child watched closely by doctors so that they can treat any problems quickly if they come up. 

Treatment by type and stage of Wilms tumor

Below are some of the most common treatment approaches for patients with Wilms tumors. Most children with this type of cancer are treated in clinical trials developed by the Children's Oncology Group. The goal of these studies is to cure as many children as possible while limiting side effects by giving as little treatment as is necessary. This is done by comparing the current best treatment with one the doctors think might be better. Because of this, treatment may differ slightly from those described below in some cases.

Treatment for Wilms tumor is based mainly on the stage of the cancer and whether its histology (appearance under the microscope) is favorable or unfavorable. In the United States, doctors prefer to use surgery as the first treatment in most cases, and then give chemotherapy (and possibly radiation therapy) afterward. In Europe, doctors prefer to begin the chemotherapy before surgery. The results seem to be about the same.

In most cases, the stage and histology of the cancer are actually determined when surgery is done to remove the cancer, because the true extent of the tumor often can’t be determined by imaging tests alone. The findings from surgery are then used to guide further treatment. But sometimes it is clear that the cancer has already spread beyond the kidney even before surgery is done, based on imaging tests. This may affect the order in which treatments are given, as well as the extent of surgery.

Stage I :These tumors are only in the kidney. Surgery (radical nephrectomy) has completely removed the tumor along with the entire kidney, nearby structures, and some nearby lymph nodes.

Favorable histology: Children younger than 2 years with small tumors (weighing less than 550 grams) may not need further treatment, such as chemotherapy. But they need to be watched closely because the chance the cancer will come back is slightly higher than if they had chemotherapy. If the cancer does come back, chemotherapy with the drugs actinomycin D (dactinomycin) and vincristine (and possibly more surgery) is very likely to be effective at this point.

For children older than 2 and for those of any age who have larger tumors, surgery is usually followed by chemotherapy with actinomycin D and vincristine. If the tumor cells have certain chromosome changes, the drug doxorubicin (Adriamycin) may be given as well. The chemotherapy is given for several months.

Unfavorable histology: For children of any age who have tumors with unfavorable histology, surgery is usually followed by radiation therapy to the area of the tumor, along with chemotherapy with actinomycin D, vincristine, and doxorubicin (Adriamycin) for several months.

Stage II: These tumors have grown outside the kidney into nearby tissues, but surgery (radical nephrectomy) was able to remove all visible signs of cancer.

Favorable histology: After surgery, standard treatment is chemotherapy with actinomycin D and vincristine. If the tumor cells have certain chromosome changes, the drug doxorubicin (Adriamycin) may be given as well. The chemotherapy is given for several months.

Unfavorable histology with focal (only a little) anaplasia: When the child recovers from surgery, radiation therapy is given to the abdomen for several days. When this is finished, chemotherapy (doxorubicin, actinomycin D, and vincristine) is given for about 6 months.

Unfavorable histology with diffuse (widespread) anaplasia: After surgery, these children get radiation to the abdomen for several days. This is followed by a more intense type of chemotherapy using the drugs vincristine, doxorubicin, etoposide, cyclophosphamide, and carboplatin, along with mesna (a drug that protects the bladder from the effects of cyclophosphamide), which is given for about 6 months.

Stage III :These tumors were not removed completely with surgery because of their size or location or for other reasons. In some cases, surgery to remove the tumor (radical nephrectomy) may be postponed until other treatments are able to shrink the tumor first (see below).

Favorable histology: Treatment is usually surgery if it can be done, followed by radiation therapy to the abdomen over several days. This is followed by chemotherapy with 3 drugs (actinomycin D, vincristine, and doxorubicin) for about 6 months.

Unfavorable histology with focal (only a little) anaplasia: Treatment begins with surgery if it can be done, followed by radiation therapy to the abdomen for several days. This is followed by chemotherapy, usually with 3 drugs (actinomycin D, vincristine, and doxorubicin) for about 6 months.

Unfavorable histology with diffuse (widespread) anaplasia: Treatment begins with surgery if it can be done, followed by radiation therapy to the abdomen for several days. This is followed by chemotherapy, usually with the drugs vincristine, doxorubicin, etoposide, cyclophosphamide, and carboplatin, along with mesna (a drug that protects the bladder from the effects of cyclophosphamide). Chemotherapy lasts about 6 months.

In some instances the tumor may be very large or may have grown into nearby blood vessels or other structures so that it cannot be removed safely. In these children a small biopsy sample is taken from the tumor to be sure that it is a Wilms tumor and to determine its histology. Then chemotherapy is started. If the tumor doesn’t shrink enough with chemotherapy, then radiation therapy is given. Usually the tumor will shrink enough within several weeks so that a radical nephrectomy can be done. Chemotherapy will be started again after surgery. If radiation was not given before surgery, it is given after surgery.

Stage IV:These tumors have already spread to distant parts of the body at the time of diagnosis. As with stage III tumors, surgery to remove the tumor (radical nephrectomy) may be the first treatment, or it may need to be delayed until other treatments can shrink the tumor (see below).

Favorable histology and unfavorable histology with focal (only a little) anaplasia: Standard treatment is usually surgery, followed by radiation therapy to the abdomen. The entire abdomen will be treated if there is still some cancer in the abdomen. If the cancer has spread to the lungs, low doses of radiation will also be given to that area. This is followed by chemotherapy, usually with 3 drugs (actinomycin D, vincristine, and doxorubicin) for about 6 months.

Unfavorable histology with diffuse (widespread) anaplasia: Treatment usually begins with surgery, followed by radiation therapy to the abdomen. The entire abdomen will be treated if there is still some cancer in the abdomen. Low doses of radiation will also be given to both lungs if there is spread to the lungs. This is followed by chemotherapy with the drugs vincristine, doxorubicin, etoposide, cyclophosphamide, and carboplatin, along with mesna given for about 6 months.

If the tumor is too large or has grown too extensively to be safely treated with surgery first, a small biopsy sample may be taken from the tumor to be sure that it is a Wilms tumor and to determine its histology. Chemotherapy and/or radiation therapy may then be used to shrink the tumor. Surgery may be an option at this point. This would be followed by more chemotherapy (and radiation therapy if it wasn't given already).

For stage IV cancers that have spread to the liver, surgery may be an option to remove any liver tumors that still remain after chemotherapy and radiation therapy.

Stage V: Treatment for children with tumors in both kidneys is unique for each child, although it typically includes surgery, chemotherapy, and radiation therapy at some point.

Biopsies (tissue samples) of tumors in both kidneys and of nearby lymph nodes may be taken first, although not all doctors feel this is needed because when both kidneys have tumors, the chance that they are Wilms tumors is very high.

Chemotherapy is typically given first to try to shrink the tumors. The drugs used will depend on the extent and histology (if known) of the tumors. After about 6 weeks of chemotherapy, surgery (partial nephrectomy) may be done to remove the tumors if enough normal kidney tissue can be left behind. If the tumors haven’t shrunk enough, treatment may include more chemotherapy or radiation therapy for about another 6 weeks. Surgery (either partial or radical nephrectomy) may then be done. This is followed by more chemotherapy, possibly along with radiation therapy if it hasn’t been given already.

If not enough functioning kidney tissue is left after surgery, a child may need to be placed on dialysis, a procedure where a special machine filters waste products out of the blood several times a week. If there is no evidence of any cancer after a year or two, a donor kidney transplant may be done.

Recurrent Wilms tumor: The prognosis and treatment for children with Wilms tumor that recurs (comes back after treatment) depends on their prior treatment, the cancer's histology (favorable or unfavorable), and where it recurs. The outlook is generally better for recurrent Wilms tumor with the following features:

Favorable histology

Initial stage of I or II

Initial chemotherapy with vincristine and actinomycin D only

No previous radiation therapy

Recurrence at least 12 months after initial diagnosis

The usual treatment for these children is surgery to remove the recurrent cancer (if possible), radiation therapy (if not already given to the area), and chemotherapy, often with drugs different from those used during first treatment.

What happens after treatment for Wilms tumor?