Complete necrosis induced by preoperative chemotherapy in Wilms tumor as an indicator of low risk: report of the international society of paediatric oncology (SIOP) nephroblastoma trial and study 9

Abstract

Background: The SIOP Nephroblastoma therapeutic protocols include a period of preoperative chemotherapy followed by nephrectomy and a period of postoperative chemotherapy. From the outset, identification of low-risk groups has been an aim of the SIOP Nephroblastoma Trials and Studies. Now that 90% of children with Wilms tumor can be cured, attention is even more focused on the identification of patients who could benefit from less aggressive postoperative therapy, thus minimizing the morbidity and late effects associated with treatment. The prognostic implications of total necrosis in nephroblastoma after chemotherapy have not been investigated hitherto.

Procedure: Between November 1, 1987 and June 30, 1993, 599 patients referred to the SIOP-9 Nephroblastoma Trial and Study were preoperatively treated and classified as stages I-IV nonanaplastic Wilms tumor.

Results: Of these 599 patients, pathologic examination of the nephrectomy specimen revealed a completely necrotic Wilms tumor (CNWT) with no viable tumor remaining in 59 (10%): these comprised 37 stages I-III and 22 stage IV. Of these patients, 58 (98%) had no evidence of disease at 5 years vs. 90% for the rest of the cohort (P < 0.05). Stages I-III patients represented 63% of CNWT and had a 97% overall survival rate. The only death was related to veno-occlusive disease and occurred in a stage I patient in the month following nephrectomy. Stage IV patients represented 37% of CNWT (vs. only 10% of all other cases of unilateral nonanaplastic Wilms tumor) and had a 100% rate of survival. Children with CNWT were older (mean 59 months vs. 43 months); their tumor at diagnosis was larger and had regressed more significantly at subsequent ultrasound examination. The data also uphold the hypothesis that Wilms tumors of blastemic pattern are most aggressive, but also are extremely responsive to chemotherapy.

Conclusions: Patients with unilateral nonanaplastic WT that showed total necrosis following preoperative chemotherapy had excellent outcome and should benefit from less aggressive postoperative treatment in further trials. Other very responsive tumors, such as Wilms with <10% viable tumor, should also be assessed.