Abstract

Abstract Background In the fifth National Wilms Tumor Study, patients received vincristine and dactinomycin (VA) without radiation for stage I focal anaplastic Wilms tumor (FAWT) and VA plus doxorubicin (DD4A) and radiation for stage II–IV FAWT. Four‐year event‐free survival (EFS) and overall survival (OS) for stage I FAWT were 67.5% and 88.9% and for stage IV FAWT were 61.4% and 71.6%, respectively. Therapy intensification for stage I and IV FAWT was evaluated as secondary objectives in AREN0321. Methods Central review in the AREN03B2 Renal Tumors Classification, Biology, and Banking Study confirmed patient stage and tumor histology. Patients were then enrolled in AREN0321 and received DD4A with radiation for stage I–III FAWT and vincristine, doxorubicin, cyclophosphamide, carboplatin, and etoposide (UH‐1/revised UH‐1) with radiation for stage IV FAWT. Outcomes of patients with FAWT who were treated in AREN0321 ( n = 25) and in AREN03B2 ( n = 20) treated as per AREN0321 were analyzed. Results In the pooled data analysis from AREN0321 and AREN03B2, 4‐year EFS and OS were both 100% for stage I–II FAWT ( n = 21), 82.4% (95% CI, 66.1%–100%) and 87.8% (95% CI, 73.4%–100%) for stage III FAWT ( n = 17), respectively, and both 85.7% (95% CI, 63.3%–100%) for stage IV FAWT ( n = 7). Four patients enrolled in AREN0321 had events: treatment failure occurred in three patients with stage III FAWT, and one treatment‐related death was observed in a patient with stage IV FAWT following revised UH‐1. No EFS or OS events occurred in patients with FAWT enrolled in AREN03B2 only. Conclusions Patients with stage I and II FAWT have outstanding survival when treated with DD4A and radiation. Intensification of therapy may have improved survival for stage IV FAWT, albeit with an increased toxicity risk.