Peter F. Ehrlich

Introduction The purpose of this study is to examine the outcomes in children with anaplastic bilateral Wilms tumor (BWT) from study AREN0534 in order to define potential prognostic factors and areas to target in future clinical trials. Methods Demographic and clinical data from AREN0534 study patients with anaplasia (focal anaplasia [FA], or diffuse anaplasia [DA]) were compared. Event‐free survival (EFS) and overall survival (OS) were reported using Kaplan–Meier estimation with 95% confidence bands, and differences in outcomes between FA and DA compared using log‐rank tests. The impact of margin status was analyzed. Results Twenty‐seven children who enrolled on AREN0534 had evidence of anaplasia (17 DA, 10 FA) in at least one kidney and were included in this analysis. Twenty‐six (96%) had BWT. Nineteen percent had anaplastic histology in both kidneys (four of 17 DA, and one of 10 FA). Forty‐six percent with BWT had bilateral nephron‐sparing surgery (NSS); one child who went off protocol therapy, eventually required bilateral completion nephrectomies. Median follow‐up for EFS and OS was 8.6 and 8.7 years from enrollment. Four‐ and 8‐year EFS was 53% [95% confidence interval (CI): 34%–83%] for DA; 4‐year EFS was 80% [95% CI: 59%–100%], and 8‐year EFS 70% [95% CI: 47%–100%] for FA. Three out of 10 children with FA and eight out of 17 children with DA had events. EFS did not differ statistically by margin status ( p = .79; HR = 0.88). Among the six children who died (five DA, one FA), all experienced prior relapse or progression within 18 months. Conclusion Events in children with DA/FA in the setting of BWT occurred early. Caution should be taken about interpreting the impact of margin status outcomes in the context of contemporary multimodal therapy. Future targeted investigations in children with BWT and DA/FA are needed.