The current AREN0532 Children’s Oncology Group (COG) Wilms tumor study is testing the hypothesis that children less than 2 years old with stage I favorable histology Wilms tumor weighing less than 550 grams can be effectively managed with nephrectomy only. A decisiontree analysis supports this as a reasonable strategy[1
] and preliminary observations in eight patients demonstrated this to be plausible[2
]. A larger study undertaken by Green et al[3
], was halted because a stopping rule was reached when the relapse rate exceeded 10%. This stopping rule was set anticipating that the salvage rate would be only 50%. However, a much higher rate of more than 90% was observed[3
] and in longer term follow up this has been maintained[4
Advantages of nephrectomy alone as a treatment strategy in this very young patient population include avoiding chemotherapy in the majority (estimated to be more than 85%), thereby limiting the risk of veno-occlusive disease (up to 5%) [5
], decreasing clinic or hospital visits, and avoiding central venous access devices. Standard treatment in this group of patients in North America would usually be considered as regimen EE4A (vincristine and actinomycin D × 18 weeks) although vincristine alone has also been used successfully[6
]. A disadvantage of the nephrectomy only strategy is that patients with recurrence typically receive a more intensive regimen than they would have with Regimen DD4A (vincristine, actinomycin D, doxorubicin×24 weeks and involved field radiotherapy). In addition there is a theoretically greater psychological burden for parents during the observation period[7
Review of National Wilms Tumor Study-5 (NWTS-5) data demonstrated that approximately 75% of eligible patients were enrolled on the observation only arm of the Green et al study (Breslow NWTS personal communication). Those who did not enroll were not formally surveyed, but sporadically recorded reasons for lack of enrollment included parental refusal, physician choice and ‘medically ineligible’. The current observation only arm of the AREN0532 study was projected to accrue 20–25 patients per year over 5 years based on the experience of NWTS5. We have noted a slightly lower accrual rate on the observation only arm compared to other renal tumor studies and exploration of this observation demonstrated that approximately 40% of eligible patients were not enrolled.
We therefore surveyed all institutions with potentially eligible patients who did not enroll on AREN0532 to determine reasons and outcomes for non-enrolled patients. We speculated that a large portion of non-enrollment was due to parental refusal, or that treating physicians consider nephrectomy only the current standard of care. Understanding the determinants of enrollment will be important to future study design, especially when a reduction in therapy question is at stake, and potentially important in addressing parental concerns.