Wilms Tumor Treatment & Management

The usual approach in most patients is nephrectomy followed by chemotherapy, with or without postoperative radiotherapy. Table 1 summarizes the current approach to patients with favorable histology Wilms tumor according to Children’s Oncology Group (COG) studies. Children found to have loss of heterozygosity at 1p and 16q receive more aggressive chemotherapy because they have a worse prognosis than do children without this heterozygosity loss.^[5]

Table 1. Current Approach to Favorable Histology Wilms Tumor by Stage (Open Table in a new window)

Currently, patients enrolled in the COG AREN0321 protocol for high risk Wilms tumor are treated as follows:

• Focal anaplastic stage I-III Wilms tumors and diffuse anaplastic stage I Wilms tumors - Nephrectomy followed by vincristine, actinomycin-D, and doxorubicin in addition to local radiotherapy
• Focal anaplastic stage IV Wilms tumors and diffuse anaplastic stage II-III tumors –Patients undergo the same treatment, with the addition of cyclophosphamide, etoposide, and carboplatin
• Stage IV diffuse anaplastic Wilms tumors - More aggressive treatment is delivered; nephrectomy is followed by initial irinotecan and vincristine administration, which in turn is followed by actinomycin-D, doxorubicin, cyclophosphamide, carboplatin, etoposide, and radiotherapy.

Management of lung metastasis

Patients with negative findings on chest radiography and positive findings on CT scanning of the lungs require tissue diagnosis of the lung nodules because several conditions (eg, histoplasmosis, atelectasis, pseudotumor, intrapulmonary lymph node, pneumonia) can mimic pulmonary metastases.

NWTS studies have not shown any survival benefit from treating nodules that have negative chest radiograph findings but positive CT scan findings with whole lung radiotherapy. In one study, patients treated with whole lung radiotherapy had fewer lung relapses but suffered higher treatment-related deaths.^[27]

In the current COG study, patients with favorable histology Wilms tumor with lung metastasis and no other sites of distant spread or presence of 1p and 16q deletion undergo 6 weeks of actinomycin-D, doxorubicin, and vincristine. If a complete response in the pulmonary nodules occurs, then patients are not given whole lung irradiation.

Management of bilateral Wilms tumor

One report of patients with bilateral Wilms tumor treated according to the National Wilms Tumor Study-4 demonstrated that preservation of renal parenchyma is possible following initial preoperative chemotherapy. Patients with bilateral Wilms tumor had an increased incidence of end-stage renal failure, including patients who did not have bilateral nephrectomies. Further investigation is required to determine the need for earlier biopsy in nonresponsive tumors and earlier definitive surgery in patients with unfavorable histology.^[28]

Additional treatment considerations

Whether patients younger than age 6 months who have stage III disease should receive radiation therapy is controversial. In the NWTS-5 protocol, physicians were required to call an NWTS-5 radiation oncologist to discuss guidelines. The late toxicity of irradiating young children has been a concern for many, even with relatively low doses of radiation.

Female patients have an increased risk of giving birth prematurely. Possible explanations include loss of elasticity of the uterine wall, surgical adhesions, and a high incidence of uterine anomalies.

As many as one third of patients with Wilms tumor present with hypertension. Their blood pressure usually normalizes after nephrectomy, but they occasionally require prolonged therapeutic intervention.

Activity

No precautions regarding activity are advised, although the patient and his or her parents should be aware that the patient will have only 1 kidney after therapy. Activities that carry an inherent risk of kidney injury, such as boxing and hockey, should be avoided.

Consultations

The patient should be referred to a pediatric surgeon, a pediatric oncologist, and, in some cases, a radiation oncologist.

About 5-10% of patients present with acquired von Willebrand disease at the time of diagnosis. Several hypothesis have been postulated to explain acquired von Willebrand disease, including absorption of the von Willebrand factor (vWF) by tumor cells, hyperviscosity caused by elevated serum levels of hyaluronic acid, and an immunoglobulin G (IgG)–type antibody that prevents aggregation of normal platelet cells (immunologic inactivation).

If present, excessive bleeding during surgery should be expected and prenephrectomy therapy should be started. Whenever possible, the use of blood derivatives should be avoided because of the potential to transmit viral infections. Instead, an initial trial of desmopressin (DDAVP), a drug that promotes the release of vWF from storage sites, is recommended. DDAVP has been effective in most patients with type I von Willebrand disease and in some with type II disease. If DDAVP is administered, fluid and electrolyte balance should be carefully monitored. If DDAVP is ineffective, cryoprecipitator (a specific vWF concentrate) should be administered.

The lungs are the most common site of relapse. This site is affected in more than two thirds of children who have a relapse. The tumor bed is the site of relapse only in about one fourth of patients. The brain and the bones are not usual sites of relapse for Wilms tumors with favorable histology.

The patient must be examined at the follow-up clinic after he or she completes all therapy. The purpose of follow-up care is to check for recurrence and for late effects of therapy.

Table 2 outlines the types and frequency of radiographic studies during follow-up according to the NWTSG.^[29] For follow-up of late effects and recommended studies, please refer to the Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers, from the COG.

Table 2. Recommended Follow-Up Imaging Studies in Children with Wilms Tumor Without Metastasis at Diagnosis^* (Open Table in a new window)