Chemotherapy

Preoperative chemotherapy before nephrectomy is indicated in the following situations, which have been listed previously under situations requiring a biopsy:[228,238,243-246]

For more information, see the Diagnostic and Staging Evaluation for Wilms Tumor section.

A large contemporary series included 124 patients with Wilms tumor and intracaval extension who were treated at North American centers. Most patients (82%) received a three-drug neoadjuvant chemotherapy regimen. Neoadjuvant chemotherapy reduced the need for cardiopulmonary bypass and also avoided the complexity of intrahepatic caval thrombus resection.[246]

Preoperative chemotherapy follows a biopsy. The biopsy may be performed through a flank approach.[178,247-251] Adequate tissue is essential for accurate histological assessment and molecular studies. Preoperative chemotherapy includes doxorubicin in addition to vincristine and dactinomycin unless anaplastic histology is present. In these cases, chemotherapy then includes treatment with regimen I (see Table 2). The chemotherapy generally makes tumor removal easier by decreasing the size and vascular supply of the tumor. Chemotherapy may also reduce the frequency of surgical complications.[173,178,238,243,252,253]

In a meta-analysis that investigated the effect of neoadjuvant chemotherapy on thrombus viability for Wilms tumor where intravascular extension was defined as any Wilms tumor with extension beyond the renal vein. Neoadjuvant chemotherapy was found to be effective in achieving thrombus nonviability in around 50% of patients with tumor extension into the inferior vena cava. No added benefit was identified from extended cycles of neoadjuvant chemotherapy. Most patients received chemotherapy consisting of dactinomycin and vincristine with or without doxorubicin.[254]

In North America, the use of preoperative chemotherapy in patients with evidence of a contained preoperative rupture has been suggested to avoid intraoperative spill, but this is controversial.[255,256] The preoperative diagnosis of a contained retroperitoneal rupture on CT is difficult, even for experienced pediatric radiologists.[162]

All infants younger than 12 months (including newborns) who will be treated with chemotherapy require a 50% reduction in chemotherapy dose compared with the dose given to older children.[257] Dosing for infants (younger than 12 months) is calculated per kilogram of weight, not body surface area. This reduction diminishes the toxic effects reported in children in this age group enrolled in NWTS studies while maintaining an excellent overall outcome.[258]

Liver function tests in children with Wilms tumor are monitored closely during the early course of therapy because severe hepatic toxic effects (including sinusoidal obstructive syndrome, which was previously called veno-occlusive disease) have been reported in these patients.[259,260] In a cohort of 8,862 children with renal tumors from the NWTS-3, -4, and -5 trials, the incidence of severe hepatopathy was low (0.8%). Careful reintroduction of chemotherapy appeared to be feasible for most patients who developed severe chemotherapy- and/or radiation therapy–induced liver toxicity.[261] Dactinomycin or doxorubicin should not be administered during radiation therapy.

Patients who develop renal failure while undergoing therapy can continue chemotherapy with vincristine, dactinomycin, and doxorubicin. Vincristine and doxorubicin can be given at full doses. However, dactinomycin is associated with severe neutropenia. Dose reductions for these agents may not be necessary, but accurate pharmacological and pharmacokinetic studies are needed while the patient is receiving therapy.[262,263]

Augmentation of therapy improves EFS for patients with FH Wilms tumor and loss of heterozygosity of 1p and 16q. In the AREN0532 (NCT00352534) and AREN0533 (NCT00379340) trials, patients with stage I and stage II FH Wilms tumor who were treated with the DD-4A regimen (dactinomycin, vincristine, and doxorubicin) demonstrated a 4-year EFS rate of 87.3%, compared with the 4-year EFS rate of 68.8% (P = .042) for stage I and stage II patients treated on the NWTS-5 trial. Patients with stage III and stage IV disease had a 4-year EFS rate of 90.2% when treated with regimen M (see Table 2), compared with a 61.3% 4-year EFS rate (P = .001) for stage III and stage IV patients treated on the NWTS-5 trial. Trends toward improved 4-year OS rates were seen in stage I and II patients and in stage III and IV patients.[264][Level of evidence C2]

Postoperative radiation therapy to the tumor bed is required when a biopsy is performed or in the setting of local tumor stage III. In a study of 1,488 patients with Wilms tumors who underwent surgery and radiation therapy, delay in starting radiation therapy after surgery of greater than 14 days was associated with an increased risk of mortality for patients with nonmetastatic Wilms tumor.[265][Level of evidence C1]

Table 2 describes the accepted chemotherapy regimens used to treat Wilms tumor.