TUMOR CHARACTERISTICS, TREATMENT APPROACH and OUTCOMES in CHILDREN with WAGR SYNDROME and WILMS TUMOR – an ANALYSIS of the INTERNATIONAL WAGR SYNDROME ASSOCIATION REGISTRY (IWSA)

Background: WAGR syndrome (Wilms Tumor Aniridia Genitourinary Malformations and range of development delays) is a rare disease. Children with WAGR have a predisposition to Wilms Tumor (WT). We present an epidemiological analysis of tumor characteristics, treatment and associated congenital risk factors in WAGR patients with WT.

Methods: The IWSA conducted a survey between 2015-2021. Demographic, surgical, chemotherapeutic, radiotherapy and congenital anomalies that predisposed to WT were analyzed. Categorical comparisons were made with chi-squared test and continuous comparisons were made using t-test and ANOVA.

Results: Parents of 145 children with WAGR completed the questionnaire, of whom 64(44.1%) had WT and 12(8.2%) had nephrogenic rests. Median length of follow-up from the diagnosis of WT was 6.7 years (IQR 2.5-13.4 years), median age at diagnosis was 26 months (IQR 18-26 months). One child was diagnosed after 5 years of age. Fifty-four(84.3%) had unilateral stage 1-2 disease and 59(92.1%) had favorable histology WT(FHWT). One child developed bilateral WT (BWT); only 2 had stage IV disease. Treatment included preoperative chemotherapy for 47 children and primary nephrectomy for 15. At least one kidney was removed in 38. Nephron sparing surgery (NSS) was associated with preoperative chemotherapy 19/24(79.1%) compared to upfront surgery 5/24(20.8%). The duration of chemotherapy was between 1-12 months in 50 children and was more prolonged in 8 (duration was unknown for 6 children). Chemotherapy included a two-drug regimen for 21 and a three-drug or more intensive therapy in 34. Relapse occurred in 3(4.6%) children. There was one death. No congenital genitourinary anomalies in children with WAGR (e.g. hypospadias, cryptorchidism) were associated with the development of WT.

Conclusion: In this analysis of children with WAGR syndrome and WT their disease was primarily unilateral and FHWT with infrequent relapse. Regrettably, NSS was performed in only 1/3 of children.