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Long-term adverse effects of modern Wilms tumour therapies: implications for monitoring

Nature Reviews Urology (2026)Cite this article

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Abstract

Wilms tumour is the most common kidney tumour in children. Owing to global collaboration and advances in clinical care, 90% of affected children, including those with metastatic disease, can now be cured. Further improvements in this outstanding outcome will depend on implementing strategies to prevent treatment-related mortality and gaining insights into the molecular and clinical drivers of Wilms tumour to introduce tailored therapies. The main treatments for Wilms tumour are nephrectomy and chemotherapy, with radiotherapy used selectively. Wilms tumour therapies can lead to long-term chronic health conditions, such as chronic kidney disease, infertility, second primary neoplasms and cardiovascular disease, despite the use of risk-adapted protocols to optimize the therapeutic index. Research into therapy de-escalation has been enhanced by survivor cohort studies investigating the chronic health conditions associated with specific Wilms tumour therapies. Understanding these relationships and which patients are most susceptible to specific toxic effects is crucial for counselling Wilms tumour survivors and their health-care providers on survivorship care planning. A classification framework could stratify survivors by their risk of treatment-related long-term morbidity, to tailor long-term follow-up monitoring and care.

Key points

  • Nearly one-third of Wilms tumour survivors experience at least one grade 3–5 chronic health condition (CHC) by age 35 years. The most common CHCs are cardiovascular disease, chronic kidney disease and secondary primary neoplasms.

  • Knowing which patients with Wilms tumour are most vulnerable to late toxic effects is crucial for counselling survivors and their health-care providers on long-term survivorship care planning.

  • An improved understanding of genetic predispositions to kidney impairment and secondary primary neoplasms might help refine future screening strategies for at-risk individuals.

  • Radical nephrectomy is the standard surgical approach in Wilms tumour treatment and can have lasting effects on kidney and cardiovascular function.

  • Treatment de-escalation efforts in Wilms tumour have led to reduced long-term morbidity and mortality, lowering the health-care burden.

  • Novel radiotherapy techniques that minimize irradiated field volumes could reduce the risk of radiotherapy-related CHCs.

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Fig. 1: Treatment planning and dosimetry comparison between photon and proton therapy for Wilms tumour.

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Change history

  • 10 February 2026

    In the version of this article initially published, the email listed for Filippo Spreafico was incorrect; the email is now amended in the HTML and PDF versions of the article.

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Authors and Affiliations

  1. Oncology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy

    Filippo Spreafico

  2. Department of Medical Oncology and Hematology, Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Giovanna Gattuso, Marta G. Podda, Olga Nigro, Valeria Colombo, Maura Massimino & Monica Terenziani

  3. Department of Radiology and Radiotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Sabina Vennarini

  4. Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Antonio Mastrangelo & Giovanni Montini

  5. Infertility Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Francesca Filippi

  6. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

    Giovanni Montini

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F.S., M.G.P., O.N., V.C., S.V., A.M., F.F. and M.T. researched data for the article. F.S., G.G., A.M., F.F., G.M., M.M. and M.T. contributed substantially to discussion of the content. F.S., G.G., M.G.P., O.N., S.V., V.C., F.F., G.M. and M.T. wrote the article. F.S., A.M., G.M. and M.T. reviewed and/or edited the manuscript before submission.

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Spreafico, F., Gattuso, G., Podda, M.G. et al. Long-term adverse effects of modern Wilms tumour therapies: implications for monitoring. Nat Rev Urol (2026). https://doi.org/10.1038/s41585-026-01126-x

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