Treatment by Type and Stage of Wilms Tumor

In the United States, most children with Wilms tumors 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 what is described here.

Treatment for Wilms tumor is based mainly on the stage of the cancer and whether its histology (how it looks under the microscope) is favorable or anaplastic. Other factors can influence treatment as well, including:

• The child’s age
• If the tumor cells have certain chromosome changes
• The size of the main tumor

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 start the chemotherapy before surgery. The results from these approaches seem to be about the same.

Most often, 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 doctors use what they learn during surgery to guide further treatment. But sometimes it’s clear that the cancer has already spread beyond the kidney even before surgery is done, based on imaging tests. This can affect the order in which treatments are given, as well as the extent of surgery.

Stage I

These tumors are only in the kidney, and surgery 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 after surgery. But they need to be watched closely because the chance the cancer will come back is slightly higher than if they also got chemo. If the cancer does come back, the chemo drugs actinomycin D (dactinomycin) and vincristine (and possibly more surgery) are 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 chemo for several months, with the drugs actinomycin D and vincristine. If the tumor cells have certain chromosome changes, the drug doxorubicin (Adriamycin) may be given as well.

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

Stage II

These tumors have grown outside the kidney into nearby tissues, but surgery has removed all visible signs of cancer.

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

Anaplastic histology, with focal (only a little) anaplasia: When the child recovers from surgery, radiation therapy is given over several weeks. When this is finished, chemo (doxorubicin, actinomycin D, and vincristine) is given for about 6 months.

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

Stage III

Surgery cannot remove these tumors completely because of their size or location or for other reasons. In some cases, surgery 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 over several days. This is followed by chemo with 3 drugs (actinomycin D, vincristine, and doxorubicin). If the tumor cells have certain chromosome changes, the drugs cyclophosphamide and etoposide may be given as well. Chemo is given for about 6 months.

Anaplastic histology, with focal (only a little) anaplasia: Treatment starts with surgery if it can be done, followed by radiation therapy over several weeks. This is followed by chemo, usually with 3 drugs (actinomycin D, vincristine, and doxorubicin) for about 6 months.

Anaplastic histology, with diffuse (widespread) anaplasia: Treatment starts with surgery if it can be done, followed by radiation therapy over several weeks. This is followed by chemo, usually with the drugs vincristine, doxorubicin, etoposide, cyclophosphamide, and carboplatin, along with mesna (a drug that helps protect the bladder from the effects of cyclophosphamide). Chemo 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 can’t be removed safely. In these children, a small biopsy sample is taken from the tumor to be sure that it’s a Wilms tumor and to determine its histology. Then chemo is started. Usually the tumor will shrink enough within several weeks so that surgery can be done. If not, then radiation therapy might be given as well. Chemo will be started again after surgery. If radiation was not given before surgery, it’s 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 might be the first treatment, but it might need to be delayed until other treatments can shrink the tumor (see below).

Favorable histology: Surgery to remove the tumor is the first treatment if it can be done, followed by radiation therapy. The entire abdomen will be treated if there is still some cancer left after surgery. If the cancer has spread to the lungs, low doses of radiation might also be given to that area. This is followed by chemo, usually with 3 drugs (actinomycin D, vincristine, and doxorubicin) for about 6 months. If the tumor cells have certain chromosome changes, the drugs cyclophosphamide and etoposide may be given as well.

Anaplastic histology: Treatment might start with surgery if it can be done, followed by radiation therapy. The entire abdomen will be treated if there is still some cancer left after surgery. Low doses of radiation will also be given to the lungs if the cancer has spread there. This is followed by chemo with the drugs vincristine, doxorubicin, etoposide, cyclophosphamide, and carboplatin, along with mesna given for about 6 months. If the tumor cells have diffuse (widespread) anaplasia, some doctors might try the chemo drugs irinotecan and vincristine first instead (although this is not yet a commonly used treatment). The treatment would then be adjusted if the tumor shrinks in response to these drugs.

If the tumor is too large or has grown too much to be removed safely with surgery first, a small biopsy sample may be taken from the tumor to be sure that it’s a Wilms tumor and to determine its histology. Chemo and/or radiation therapy may then be used to shrink the tumor. Surgery might be an option at this point. This would be followed by more chemo 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 chemo and radiation therapy.

Stage V

Treatment for children with tumors in both kidneys is unique for each child, although it typically includes surgery, chemo, 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.

Chemo 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 chemo, 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 chemo or radiation therapy for about another 6 weeks. Surgery (either partial or radical nephrectomy) may then be done. This is followed by more chemo, 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 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 anaplastic), and where it recurs. The outlook is generally better for recurrent Wilms tumors with the following features:

• Favorable histology
• Initial diagnosis of stage I or II
• Initial chemo with vincristine and actinomycin D only
• No previous radiation therapy

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 chemo, often with drugs different from those used during first treatment.

Recurrent Wilms tumors that do not have the features above are much harder to treat. These children are usually treated with aggressive chemo, such as the ICE regimen (ifosfamide, carboplatin, and etoposide) or others being studied in clinical trials. Very high-dose chemo followed by a stem cell transplant (sometimes called a bone marrow transplant) might also be an option in this situation, although this is still being studied.