Preoperative chemotherapy prior to nephrectomy is indicated in the following situations:[10,17,20,21,22,23]
- Metachronous bilateral Wilms tumor.
- Wilms tumor in a solitary kidney.
- Extension of tumor thrombus above the level of the hepatic veins.
- Tumor involves contiguous structures whereby the only means of removing the kidney tumor requires removal of the other structures (e.g., spleen, pancreas, colon but excluding the adrenal gland).
- Pulmonary compromise due to extensive pulmonary metastases.
- Retroperitoneal rupture with free fluid contained by Gerota fascia.
Patients with massive, nonresectable unilateral tumors, bilateral tumors, or venacaval tumor thrombus extending above the hepatic veins are candidates for preoperative chemotherapy because of the risk of initial surgical resection.[10,17,20,21] Preoperative chemotherapy should follow a biopsy, except in the setting of bilateral disease (COG-AREN0534). The biopsy may be performed percutaneously through a flank approach.[24,25,26,27,28,29] Preoperative chemotherapy should include doxorubicin in addition to vincristine and dactinomycin unless there is anaplastic histology present, which then includes treatment with other agents. The chemotherapy generally makes tumor removal easier because of the decreased size and vascular supply of the tumor and may reduce the frequency of surgical complications.[17,20,29,30,31] Postoperative radiation therapy to the tumor bed is required when a biopsy is performed or in the setting of local tumor stage III.
Newborns and all infants younger than 12 months require a reduction in chemotherapy doses to 50% of those given to older children. This reduction diminishes toxic effects reported in children in this age group enrolled in NWTS studies while maintaining an excellent overall outcome. Liver function tests in children with Wilms tumor should be monitored closely during the early course of therapy based on hepatic toxic effects (sinusoidal obstructive syndrome, previously called veno-occlusive disease) reported in those patients.[34,35] Dactinomycin should not be administered during radiation therapy. Patients who develop renal failure while on therapy can continue receiving chemotherapy with vincristine, dactinomycin, and doxorubicin. Vincristine and doxorubicin can be given at full doses; however, dactinomycin is associated with severe neutropenia. Reductions in dosing these agents may not be necessary, but accurate pharmacologic and pharmacokinetic studies are needed while the patient is receiving the therapy.[36,37]