title: 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.
abstract: OBJECTIVE
  To determine if patients receiving preoperative chemotherapy with vincristine and actinomycin D for non-metastatic Wilms' tumour have a more advantageous stage distribution and so need less treatment compared to patients who have immediate nephrectomy, without adversely affecting outcome.
  
  
  METHODS
  Between 1991 and 2001, a total of 205 patients with newly diagnosed non-metastatic renal tumours, of which 186 had Wilms' histologies, were randomly assigned either to immediate surgery or to 6 weeks preoperative chemotherapy and then delayed surgery. Both groups of children received postoperative chemotherapy according to tumour stage and histology determined at the time of nephrectomy.
  
  
  RESULTS
  There was a significant improvement in the stage distribution for patients with Wilms' histologies receiving delayed surgery compared to those having immediate nephrectomy (stage I: 65.2% versus 54.3%; stage II: 23.9% versus 14.9%; stage III: 9.8% versus 29.8%, chi2 test for trend=7.02, p=0.008). This improvement resulted in 20% fewer children receiving radiotherapy or doxorubicin yet event-free and overall survivals at 5 years of 79.6% and 89.0%, respectively, were similar in the two groups.
  
  
  CONCLUSIONS
  Six weeks of preoperative chemotherapy with vincristine and actinomycin D results in a significant shift towards a more advantageous stage distribution and hence reduction in therapy, while maintaining excellent event free and overall survival in children with non-metastatic Wilms' tumour. Around 20% of survivors were therefore spared the late-effects of doxorubicin or radiotherapy. Our results suggest that all children with non-metastatic Wilms' tumour should receive chemotherapy prior to tumour resection.
authors.affiliation: Department of Pediatric Hematology/Oncology, John Radcliffe Hospital, Oxford OX3 9DU, and UKCCSG Data Centre, University of Leicester, UK. chris.mitchell@paediatrics.ox.ac.uk
authors.forename: Christopher
authors.initials: C
authors.lastname: Mitchell
authors.forename: Kathy
authors.initials: K
authors.lastname: Pritchard-Jones
authors.forename: Rosemary
authors.initials: R
authors.lastname: Shannon
authors.forename: Carolyn
authors.initials: C
authors.lastname: Hutton
authors.forename: Suzanne
authors.initials: S
authors.lastname: Stevens
authors.forename: David
authors.initials: D
authors.lastname: Machin
authors.forename: John
authors.initials: J
authors.lastname: Imeson
authors.forename: Anna
authors.initials: A
authors.lastname: Kelsey
authors.forename: Gordan M
authors.initials: GM
authors.lastname: Vujanic
authors.forename: Peter
authors.initials: P
authors.lastname: Gornall
authors.forename: Jenny
authors.initials: J
authors.lastname: Walker
authors.forename: Roger
authors.initials: R
authors.lastname: Taylor
authors.forename: Pat
authors.initials: P
authors.lastname: Sartori
authors.forename: Juliet
authors.initials: J
authors.lastname: Hale
authors.forename: Gill
authors.initials: G
authors.lastname: Levitt
authors.forename: Boo
authors.initials: B
authors.lastname: Messahel
authors.forename: Helen
authors.initials: H
authors.lastname: Middleton
authors.forename: Richard
authors.initials: R
authors.lastname: Grundy
authors.forename: Jon
authors.initials: J
authors.lastname: Pritchard
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003609:Dactinomycin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000401:mortality / Q000628:therapy*; D008297:Male; D009367:Neoplasm Staging; D009392:Nephrectomy; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D009396:Wilms Tumor / Q000401:mortality / Q000628:therapy*
chemical_list: D003609:Dactinomycin; D014750:Vincristine