Treatment of Wilms' tumor. Results of the third national Wilms' tumor study

TLDR

The study aimed to reduce therapy intensity for low‑risk Wilms’ tumor patients and identify more effective chemotherapy for high‑risk patients. A randomized trial of 1,439 patients stratified by stage (I–IV) and histology (favorable or unfavorable) assigned low‑risk patients to shorter versus standard chemotherapy, while high‑risk patients received varying doses of postoperative radiation (0–2000 cGy) and chemotherapy. Four‑year survival was 96.5% for Stage I/FH patients on 10‑week dactinomycin‑vincristine, 92.2% for Stage II/FH, 86.9% for Stage III/FH, and 73.0% for high‑risk patients receiving radiation plus multi‑agent chemotherapy; the study concluded that reduced therapy did not compromise outcomes for low‑risk patients and cyclophosphamide offered no benefit for high‑risk patients.

Abstract

The Third National Wilms' Tumor Study sought to reduce treatment for low-risk patients and find better chemotherapy for those at high risk for relapse. Eligible patients (1439) were randomized according to stage (I–IV) and histology (favorable [FH] or unfavorable [UH]), and contributed data to survival and relapse-free survival (RFS) analyses. Four-year (postnephrectomy) survival percentages and randomized treatment regimens for low-risk patients were 96.5% for 607 Stage I/FH patients who received dactinomycin (Actinomycin D [AMD], Merck Sharp & Dohme, West Point, PA) and vincristine (VCR) for 10 weeks versus 6 months; 92.2% for 278 Stage II/FH patients; and 86.9% for 275 Stage III/FH patients who received AMD + VCR ± Adriamycin (ADR, Adria Laboratories, Columbus, OH) for 15 months. Stage II/FH patients also had either zero or 2000 cGy irradiation (RT) postoperatively and Stage III/FH patients either 1000 or 2000 cGy. Four-year survival was 73.0% for 279 high-risk patients (any Stage IV, all UH) who received postoperative radiation therapy (RT) and AMD + VCR + ADR ± cyclophosphamide (CPM). Statistical analysis of survival and RFS experience shows that the less intensive therapy does not worsen results for low-risk patients and CPM does not benefit those at high risk.