Outcome and Prognostic Factors in Stage III Favorable-Histology Wilms Tumor: A Report From the Children's Oncology Group Study AREN0532

Fernandez, CV et al, 2018, Journal of Clinical Oncology

Link to abstract



This is a report on the outcomes of children with stage III favorable-histology Wilms tumours treated on the most recently closed COG trial AREN0532. The goal of the prospective therapeutic cohort trial was to identify clinical and biologic variables that affect the prognosis of patients with stage III favorable-histology Wilms tumor, as well as to maintain an EFS >85% and OS >95%.


588 children with stage III disease were included whether they had upfront nephrectomy or delayed nephrectomy. Any children with evidence of metastases or with LOH of 1p AND 16q or with anaplastic histology were excluded. This was a single-arm trial with central review of imaging and pathology. All children received Regimen DD4A (vincristine, doxorubicin, and dactinomycin) as well as flank or abdominal radiation depending on the local extent of disease. 

Results Summary

Overall 4-yr EFS was 88% and 4-yr OS was 97%. Both were improved from NWTS5, the last published North American Wilms tumor trial; 116/535 children had neoadjuvant chemotherapy; 7 children with neoadjuvant chemotherapy had completely necrotic disease - none relapsed; 7 children with neoadjuvant chemotherapy had blastemal-predominant disease - five relapsed. 
A combination of positive lymph nodes and LOH of 1p OR 16q conferred worse outcome. Conversely, children without nodal metastases and no LOH of 1p or 16q had exceptionally good outcomes. Most relapses occurred early (within 2 years of diagnosis) and the majority were metastatic relapses.


This was a single-arm observational trial so comparisons to other outcomes are difficult. It is especially difficult to compare to SIOP outcomes even in children who received neoadjuvant chemotherapy because the radiation doses were different and some parts of the chemotherapy regimens differed as well. Children with high-risk post-operative histology (i.e. blastemal predominance) did not have their therapy intensified unlike in SIOP. There is also likely stage migration affecting the results of this trial as all patients with lung nodules on CT and those with LOH of 1p AND 16q were excluded in this trial but not from NWTS5. There was a trend noted toward a higher rate of delayed nephrectomy, resulting in some patients who may have had stage I or II disease being upstaged due to biopsy.

Bottom Line

There were overall good outcomes using the AREN0532 protocol of DD4A with radiation therapy, including EFS 88% and OS 97%. DD4A chemotherapy and 10-11 Gy of flank/abdo radiation after upfront nephrectomy is still the standard of care for stage III disease in North America. However, this trial indicates that there is no difference in outcome if neoadjuvant chemotherapy is used and so this is a viable option for surgically difficult cases. An association between lymph node positivity and LOH status and EFS was found to be significant. New risk groups may have also been identified based on lymph node metastases and LOH of a single chromosome. In particular, the group with no nodal metastases and no LOH may be able to have a reduction in therapy. Finally, all clinicians treating Wilms tumours should carefully consider intensification of therapy in cases of blastemal-predominance.

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