The bulk of the guidelines laid out what Dr Mullen described as an “elaborate scheme” of chemotherapy, radiation, and other therapies patients should receive depending on their risk group. Notably, recommendations are softer in some areas where there is currently less clarity around the optimal course of treatment, Dr Mullen said. That applies, for instance, to patients with tumors of favorable histology that express a loss of heterozygosity in chromosomes 1p and 16q or a gain in chromosome 1q, which are associated with increased risk of relapse.7

The COG studies AREN0532 and AREN0533 ( Identifiers: NCT00352534, NCT00379340) offered intensified therapy for patients with a finding of combined loss of heterozygosity of 1p and 16q. Patients with stage I/II disease received regimen DD4A (vincristine, dactinomycin, and doxorubicin) without radiation, while patients with stage III/IV disease received the more intense regimen M (vincristine, dactinomycin and doxorubicin alternating with cyclophosphamide and etoposide) and radiation therapy.8 The studies showed improved 4-year event-free survival in stage I/II tumors (87.3%) and stage III/IV disease (90.2%) compared with a previous trial (68.8% and 61.3% respectively; Identifier: NCT00002611), but the studies were not powered to detect differences in 4-year overall survival.

This uncertainty is reflected in the guidelines, in which patients at low risk (ie, with certain stage I/II tumors) with unilateral disease expressing these markers are recommended to either continue on an EE4A regimen (vincristine and dactinomycin) following primary nephrectomy or switch to the more intense DD4A regimen. Patients in higher risk groups (ie, stages III/IV) with unilateral disease and lung-only metastases have the option of regimen DD4A or M.

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The clinical benefits with these more intense regimens come with added risk, which should be discussed with families and put into context with the possibility of relapse, which requires marked further intensification of therapy, Dr Mullen added. As for patients with the 1q anomaly, no trial has yet studied whether intensifying therapy will lead to better outcomes. “In this in-between [stage] before the studies have been done …  it’s up to the individual provider and the family to weigh the risks of some intensification of therapy.”

“These guidelines allow us to have a central repository to have the most updated information available to us, as opposed to [having to] comb through the literature each time a patient is diagnosed,” Dr Harrison noted of the new guidelines. “Now you can look through these slides and you have a kind of algorithm that really guides the approach.”

Of course, there still remain many open questions in the treatment of Wilms tumor. “We’re curing the vast majority of children, but we’re not curing all, and we still have a lot of work to do,” Dr Harrison said. Certain subgroups are in particular need of more research, such as those with diffuse anaplastic tumors or with favorable histology who experience relapse, Dr Mullen added.  The guidelines “are kind of a living document,” she said. “Once we have new information, there is the possibility for refinement of the guidelines to continue to update what the best care is.”


  1. NCCN clinical practice guidelines in oncology (NCCN guidelines): pediatric acute lymphoblastic leukemia. National Comprehensive Cancer Network. Accessed March 16, 2021.
  2. NCCN clinical practice guidelines in oncology (NCCN guidelines): pediatric Hodgkin lymphoma. National Comprehensive Cancer Network. Accessed March 16, 2021.
  3. NCCN clinical practice guidelines in oncology (NCCN guidelines): pediatric aggressive mature B-cell lymphoma. National Comprehensive Cancer Network. Accessed March 16, 2021.
  4. NCCN clinical practice guidelines in oncology (NCCN guidelines): Wilms tumor. National Comprehensive Cancer Network. Accessed February 17, 2021.
  5. Ehrlich P, Chi YY, Chintagumpala MM et al. Results of the first prospective multi-institutional treatment study in children with bilateral Wilms tumor (AREN0534): a report from the children’s oncology group. Ann Surg. 2017;266(3), doi:10.1097/SLA.0000000000002356
  6. D’Angio CJ, Breslow N, Beckwith JB, et al. Treatment of Wilms tumor. Results of the Third National Wilms’ Tumor Study. Cancer. 1989;64(2), doi:10.1002/1097-0142(19890715)64:2<349::aid-cncr2820640202>;2-q
  7. Hing S, Lu Y, Summersgill B, et al. Gain of 1q is associated with adverse outcome in favorable histology Wilms’ tumors. Am J Pathol. 2001;158(2), doi:10.1016/S0002-9440(10)63982-X
  8. Dix DB, Fernandez CV, Chi Y, et al. Augmentation of therapy for combined loss of heterozygosity 1p and 16q in favorable histology Wilms tumor: a Children’s Oncology Group AREN0532 and AREN0533 Study Report. J Clin Oncol. 2019;37(30). doi:10.1200/JCO.18.01972