Bilateral Wilms' tumors with progressive or nonresponsive disease

Background: To provide guidelines for future cooperative group trials, we reviewed the outcomes of children with bilateral Wilms' tumors (BWTs) treated on National Wilms Tumor Study-4 (NWTS-4) who had progressive or nonresponsive disease (PNRD). Methods: NWTS-4 enrolled 3335 patients from August 1986 to September 1994 including 188 patients with BWT (5.6%). Treatment and outcome data were collected on patients with BWT. Treatment guidelines were outlined in the protocol, but patients were not on study. Results: Thirty-eight children with BWT had PNRD. Preoperative chemotherapy was given for a median of 7 months (range, 2-29 months) before definitive resection. After the initial chemotherapy regimen, 36 children went on to a second regimen, and of these, 21 children received a third regimen before resection. Eleven patients received irradiation to one or both kidneys. Pathology at resection revealed previously undiagnosed anaplasia in 3 patients (2 diffuse and 1 focal) treated for 14, 15, and 15 months before resection. A fourth patient developed a diffusely anaplastic tumor 13 months after therapy. Other pathological findings included rhabdomyomatous (4 patients) or differentiated stromal elements (10 patients) and complete necrosis (1 patient). Ten kidneys from 7 patients lacked biopsy at presentation or pathology review of those specimens. Conclusions: BWT patients with PNRD received prolonged courses of chemotherapy. Early and sequential biopsies to establish the reason for failure to respond should be obtained. This will identify anaplastic tumors managed best by early nephrectomy and intensive chemotherapy and will also distinguish differentiated tumors that are best managed with early resection, but less intensive therapy after nephrectomy.