Relapse of Wilms' tumour and detection methods: a retrospective analysis of the 2001 Renal Tumour Study Group-International Society of Paediatric Oncology Wilms' tumour protocol database

Wilms' tumour is the most common renal cancer in childhood and about 15% of patients will relapse. There is scarce evidence about optimal surveillance schedules and methods for detection of tumour relapse after therapy.

The Renal Tumour Study Group-International Society of Paediatric Oncology (RTSG-SIOP) Wilms' tumour 2001 trial and study is an international, multicentre, prospective registration, biological study with an embedded randomised clinical trial for children with renal tumours aged between 6 months and 18 years. The study covers 243 different centres in 27 countries grouped into five consortia. The current protocol of SIOP surveillance for Wilms' tumour recommends that abdominal ultrasound and chest x-ray should be done every 3 months for the first 2 years after treatment and be repeated every 4-6 months in the third and fourth year and annually in the fifth year. In this retrospective cohort study of the protocol database, we analysed data from participating institutions on timing, anatomical site, and mode of detection of all first relapses of Wilms' tumour. The primary outcomes were how relapse of Wilms' tumour was detected (ie, at or between scheduled surveillance and with or without clinical symptoms, scan modality, and physical examination) and to estimate the number of scans needed to capture one subclinical relapse. The RTSG-SIOP study is registered with Eudra-CT, number 2007-004591-39.

Between June 26, 2001, and May 8, 2015, of 4271 eligible patients in the 2001 RTSG-SIOP Wilms' tumour database, 538 (13%) relapsed. Median follow-up from surgery was 62 months (IQR 32-93). The method used to detect relapse was registered for 410 (76%) of 538 relapses. Planned surveillance imaging captured 289 (70%) of these 410 relapses. The primary imaging modality used to detect relapse was reported for 251 patients, among which relapse was identified by abdominal ultrasound (80 [32%] patients), chest x-ray (78 [31%]), CT scan of the chest (64 [25%]) or abdomen (20 [8%]), and abdominal MRI (nine [4%]). 279 (68%) of 410 relapses were not detectable by physical examination and 261 (64%) patients did not have clinical symptoms at relapse. The estimated number of scans needed to detect one subclinical relapse during the first 2 years after nephrectomy was 112 (95% CI 106-119) and, for 2-5 years after nephrectomy, 500 (416-588).

Planned surveillance imaging captured more than two-thirds of predominantly asymptomatic relapses of Wilms' tumours, with most detected by abdominal ultrasound, chest x-ray, or chest CT scan. Beyond 2 years post-nephrectomy, a substantial number of surveillance scans are needed to capture one relapse, which places a burden on families and health-care systems.

Great Ormond Street Hospital Children's Charity, the European Expert Paediatric Oncology Reference Network for Diagnostics and Treatment, The Danish Childhood Cancer Foundation, Cancer Research UK, the UK National Cancer Research Network and Children's Cancer and Leukaemia Group, Société Française des Cancers de l'Enfant and Association Leon Berard Enfant Cancéreux and Enfant et Santé, Gesellschaft für Pädiatrische Onkologie und Hämatologie and Deutsche Krebshilfe, Grupo Cooperativo Brasileiro para o Tratamento do Tumor de Wilms and Sociedade Brasileira de Oncologia Pediátrica, the Spanish Society of Pediatric Haematology and Oncology and the Spanish Association Against Cancer, and SIOP-Netherlands.

The Lancet. Oncology. 2018 Jun 27 [Epub ahead of print]

Jesper Brok, Marta Lopez-Yurda, Harm V Tinteren, Taryn D Treger, Rhoikos Furtwängler, Norbert Graf, Christophe Bergeron, Marry M van den Heuvel-Eibrink, Kathy Pritchard-Jones, Øystein E Olsen, Beatriz de Camargo, Arnauld Verschuur, Filippo Spreafico

University College London Great Ormond Street Institute of Child Health, London, UK; Department of Paediatric Oncology and Haematology, Rigshospitalet, Copenhagen, Denmark. Electronic address: ., Department of Biometrics, Netherlands Cancer Institute, Amsterdam, Netherlands., University College London Great Ormond Street Institute of Child Health, London, UK; Department of Paediatrics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Department of Paediatric Haematology and Oncology, Saarland University Hospital, Homburg, Germany., Centre Léon Bérard, Institut d'Haematology and d'Oncology Paediatric, Lyon, France., Princess Máxima Centre for Pediatric Oncology, Utrecht, Netherlands., University College London Great Ormond Street Institute of Child Health, London, UK., Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK., Instituto Nacional do Cancer, Rio de Janeiro, Brazil., Department of Pediatric Hematology and Oncology, Hôpital de la Timone Enfant, Marseille, France., Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.