To enhance risk stratification for Wilms tumour (WT) in a pre-operative chemotherapy setting, we explored the prognostic significance and optimal age cutoffs in patients treated according to International Society of Paediatric Oncology Renal Tumour Study Group (SIOP-RTSG) protocols.

Patients(6 months-18 years) with unilateral WT were selected from prospective SIOP 93-01 and 2001 studies(1993-2016). Martingale residual analysis was used to explore optimal age cutoffs. Outcome according to age was analyzed by uni- and multivariable analysis, adjusted for sex, biopsy(yes/no), stage, histology and tumour volume at surgery.

5631 patients were included; median age was 3.4 years(IQR: 2-5.1). Estimated 5-year event-free survival (EFS) and overall survival (OS) were 85%(95%CI 83.5-85.5) and 93%(95%CI 92.0-93.4). Martingale residual plots detected no optimal age cutoffs. Multivariable analysis showed lower EFS with increasing age(linear trend P<0.001). Using previously described age categories, EFS was lower for patients aged 2-4(HR 1.34, P = 0.02), 4-10(HR 1.83, P<0.0001) and 10-18 years(HR 1.74, P = 0.01) as compared to patients aged 6 months-2 years. OS was lower for patients 4-10 years(HR 1.67, P = 0.01) and 10-18 years(HR 1.87, P = 0.04), but not for 2-4 years(HR 1.29, P = 0.23). Higher stage, histological risk group and tumour volume were independent adverse prognostic factors.

Although optimal age cutoffs could not be identified, we demonstrated the prognostic significance of age as well as previously described cutoffs for EFS (2 and 4 years) and OS (4 years) in children with WT treated with pre-operative chemotherapy. These findings encourage the consideration of age in the design of future SIOP-RTSG protocols.

PloS one. 2019 Aug 19*** epublish ***

J A Hol, M I Lopez-Yurda, H Van Tinteren, M Van Grotel, J Godzinski, G Vujanic, F Oldenburger, B De Camargo, G L Ramírez-Villar, C Bergeron, K Pritchard-Jones, N Graf, M M Van den Heuvel-Eibrink

Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Department of Biometrics, Netherlands Cancer Institute, Amsterdam, The Netherlands., Department of Paediatric Surgery, Marciniak Hospital, Wroclaw, Poland., Department of Pathology, Sidra Medicine, Doha, Qatar., Department of Radiotherapy, Academic Medical Center, Amsterdam, The Netherlands., Paediatric Haematology-Oncology Program, Instituto Nacional de Cancer (INCA), Rio de Janeiro, Brazil., Department of Paediatric Oncology, Hospital Universitario Virgen del Rocío, Seville, Spain., Department of Paediatric Oncology, Institut d’Hematologie et d’Oncologie Pédiatrique, Centre Léon Bérard, Lyon, France., UCL Great Ormond Street Institute of Child Health, University College London, London, United Kingdom., Department of Paediatric Oncology & Haematology, Saarland University, Homburg, Germany.