Immediate nephrectomy versus preoperative chemotherapy in the management of non-metastatic Wilms’ tumour: Results of a randomised trial (UKW3) by the UK Children’s Cancer Study Group

Rationale for the treatment of Wilms tumour in the UMBRELLA SIOP–RTSG 2016 protocol

“…Similar to the SIOP−2001 protocol, the UMBRELLA protocol continues to recommend preoperative actinomycin D and vincristine for patients newly diagnosed with Wilms tumour aged ≥6 months, based on results of previous SIOP trials that showed tumour downstaging using this regimen 2,6,8,9,14,17 . This benefit was also independently observed in the randomized, controlled UKW3 trial conducted by the UK Children's Cancer and Leukaemia Group (UKCCLG, previously known as the UK Children's Cancer Study Group) 18 . In patients receiving preoperative chemotherapy, the use of radiotherapy or doxorubicin could be reduced by 20% compared with those treated with direct nephrectomy, with no significant difference in survival 18 .…”

“…This benefit was also independently observed in the randomized, controlled UKW3 trial conducted by the UK Children's Cancer and Leukaemia Group (UKCCLG, previously known as the UK Children's Cancer Study Group) 18 . In patients receiving preoperative chemotherapy, the use of radiotherapy or doxorubicin could be reduced by 20% compared with those treated with direct nephrectomy, with no significant difference in survival 18 . The SIOP-RTSG accounts for the risk of misdiagnosis of Wilms tumour by recommending direct surgery instead of preoperative chemotherapy for children <6 months old, and the consideration of fine-needle biopsy for patients who have unusual clinical presentations or unusual findings on imaging.…”

Rationale for the treatment of children with CCSK in the UMBRELLA SIOP–RTSG 2016 protocol

“…Preoperative chemotherapy given according to the SIOP policy has been shown to result in downstaging of paediatric renal tumours, leading to a reduction in therapy. The two regimens (SIOP and NWTS-COG) were compared in the UK Wilms Tumour trial 3 (UKW3), in which patients were randomly assigned either to immediate nephrectomy or to preoperative chemo therapy; 20% of renal tumour survivors were spared the late effects of doxorubicin and radiotherapy by treating them with preoperative chemotherapy 24 . In addition, the SIOP policy enables assessment of histological response to treatment 24 .…”

“…The two regimens (SIOP and NWTS-COG) were compared in the UK Wilms Tumour trial 3 (UKW3), in which patients were randomly assigned either to immediate nephrectomy or to preoperative chemo therapy; 20% of renal tumour survivors were spared the late effects of doxorubicin and radiotherapy by treating them with preoperative chemotherapy 24 . In addition, the SIOP policy enables assessment of histological response to treatment 24 . Upfront resection according to the NWTS and COG protocol enables immediate, accurate assessment of the histological diagnosis and tumour extent as well as the harvesting of pretherapy tumour tissue, which is useful for research purposes.…”

“…The UMBRELLA protocol recommends continuing to treat all patients with renal tumours (including CCSK) between 6 months and 16 years of age with preoperative chemotherapy (vincristine and actinomycin for localized disease and vincristine, actinomycin, and doxorubicin for metastatic disease) based on the demonstrated downstaging effect of preoperative chemotherapy, resulting in treatment reduction 24 (TABLE 2).…”