Wilms' tumour
- Overview
- Theory
- Diagnosis
- Management
- Follow up
- Resources
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
COG criteria
surgery
Upfront nephrectomy using a transperitoneal approach is recommended for patients with unilateral renal masses who do not have a known Wilms' tumour predisposition.[4]Spreafico F, Fernandez CV, Brok J, et al. Wilms tumour. Nat Rev Dis Primers. 2021 Oct 14;7(1):75. https://www.nature.com/articles/s41572-021-00308-8 http://www.ncbi.nlm.nih.gov/pubmed/34650095?tool=bestpractice.com [52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Surgeons should avoid tumour spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[48]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Wilms tumor (nephroblastoma) [internet publication]. https://www.nccn.org/guidelines/category_1 [94]de Campos Vieira Abib S, Chui CH, Cox S, et al. International Society of Paediatric Surgical Oncology (IPSO) surgical practice guidelines. Ecancermedicalscience. 2022 Feb 17;16:1356. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023308 http://www.ncbi.nlm.nih.gov/pubmed/35510137?tool=bestpractice.com
Palpation of renal vein and inferior vena cava identifies any tumour thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Suspicious metastatic lesions (hepatic or intra-abdominal) may be biopsied or resected at the time of initial surgery for diagnostic or therapeutic purposes. Decisions about extrapulmonary metastatic lesions are highly individualised.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com [106]Benedetti DJ, Varela CR, Renfro LA, et al. Treatment of children with favorable histology Wilms tumor with extrapulmonary metastases: a report from the COG studies AREN0533 and AREN03B2 and NWTSG study NWTS-5. Cancer. 2024 Mar 15;130(6):947-61. https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35099 http://www.ncbi.nlm.nih.gov/pubmed/37933882?tool=bestpractice.com
observation or post-operative chemotherapy
Treatment recommended for ALL patients in selected patient group
Favourable histology Wilms' tumours are subdivided by the Children's Oncology Group (COG) into recurrence risk categories (based on patient age, tumour weight, stage, molecular markers, and biological factors), which determine post-operative treatment.[95]Nelson MV, van den Heuvel-Eibrink MM, Graf N, et al. New approaches to risk stratification for Wilms tumor. Curr Opin Pediatr. 2021 Feb 1;33(1):40-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919941 http://www.ncbi.nlm.nih.gov/pubmed/33394739?tool=bestpractice.com [96]Dome JS, Fernandez CV, Mullen EA, et al. Children's Oncology Group's 2013 blueprint for research: renal tumors. Pediatr Blood Cancer. 2013 Jun;60(6):994-1000. http://www.ncbi.nlm.nih.gov/pubmed/23255438?tool=bestpractice.com
COG very-low-risk patients (stage I, <2 years of age, <550 g tumour weight, without loss of heterozygosity (LOH) at 11p15, without LOH at combined 1p and 16q, provided lymph nodes were sampled and proved negative: observation alone (no chemotherapy or radiotherapy).[98]Fernandez CV, Perlman EJ, Mullen EA, et al. Clinical outcome and biological predictors of relapse after nephrectomy only for very low-risk Wilms tumor: a report from Children's Oncology Group AREN0532. Ann Surg. 2017 Apr;265(4):835-40. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5145762 http://www.ncbi.nlm.nih.gov/pubmed/27811504?tool=bestpractice.com [109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com
COG low-risk patients (stage I, any age or tumour weight, without LOH at combined 1p and 16q): post-operative chemotherapy with vincristine and dactinomycin (EE-4A regimen).[109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com
COG standard-risk patients (stage I, with LOH at combined 1p and 16q): post-operative chemotherapy with vincristine, dactinomycin, and doxorubicin (DD-4A regimen).[109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com [110]Dix DB, Fernandez CV, Chi YY, et al. Augmentation of therapy for combined loss of heterozygosity 1p and 16q in favorable histology Wilms tumor: a Children's Oncology Group AREN0532 and AREN0533 study report. J Clin Oncol. 2019 Oct 20;37(30):2769-77. https://ascopubs.org/doi/10.1200/JCO.18.01972 http://www.ncbi.nlm.nih.gov/pubmed/31449468?tool=bestpractice.com
See local specialist protocol for dosing guidelines.
Primary options
EE-4A regimen
vincristine
and
dactinomycin
OR
DD-4A regimen
vincristine
and
dactinomycin
and
doxorubicin
surgery
Upfront nephrectomy using a transperitoneal approach is recommended for patients with unilateral renal masses who do not have a known Wilms' tumour predisposition.[4]Spreafico F, Fernandez CV, Brok J, et al. Wilms tumour. Nat Rev Dis Primers. 2021 Oct 14;7(1):75. https://www.nature.com/articles/s41572-021-00308-8 http://www.ncbi.nlm.nih.gov/pubmed/34650095?tool=bestpractice.com [52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Surgeons should avoid tumour spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]de Campos Vieira Abib S, Chui CH, Cox S, et al. International Society of Paediatric Surgical Oncology (IPSO) surgical practice guidelines. Ecancermedicalscience. 2022 Feb 17;16:1356. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023308 http://www.ncbi.nlm.nih.gov/pubmed/35510137?tool=bestpractice.com
Palpation of renal vein and inferior vena cava identifies any tumour thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Suspicious metastatic lesions (hepatic or intra-abdominal) may be biopsied or resected at the time of initial surgery for diagnostic or therapeutic purposes. Decisions about extrapulmonary metastatic lesions are highly individualised.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com [106]Benedetti DJ, Varela CR, Renfro LA, et al. Treatment of children with favorable histology Wilms tumor with extrapulmonary metastases: a report from the COG studies AREN0533 and AREN03B2 and NWTSG study NWTS-5. Cancer. 2024 Mar 15;130(6):947-61. https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35099 http://www.ncbi.nlm.nih.gov/pubmed/37933882?tool=bestpractice.com
post-operative chemotherapy
Treatment recommended for ALL patients in selected patient group
Favourable histology Wilms' tumours are subdivided by the Children's Oncology Group (COG) into recurrence risk categories (based on patient age, tumour weight, stage, molecular markers, and biological factors), which determine post-operative treatment.[95]Nelson MV, van den Heuvel-Eibrink MM, Graf N, et al. New approaches to risk stratification for Wilms tumor. Curr Opin Pediatr. 2021 Feb 1;33(1):40-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919941 http://www.ncbi.nlm.nih.gov/pubmed/33394739?tool=bestpractice.com [96]Dome JS, Fernandez CV, Mullen EA, et al. Children's Oncology Group's 2013 blueprint for research: renal tumors. Pediatr Blood Cancer. 2013 Jun;60(6):994-1000. http://www.ncbi.nlm.nih.gov/pubmed/23255438?tool=bestpractice.com
Chemotherapy regimen for stage II disease depends on the biology of the tumour.
COG low-risk patients (stage II, without loss of heterozygosity [LOH] at combined 1p and 16q): post-operative chemotherapy with vincristine and dactinomycin (EE-4A regimen).[109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com
COG standard-risk patients (stage II, with LOH at combined 1p and 16q): post-operative chemotherapy with vincristine, dactinomycin, and doxorubicin (DD-4A regimen).[109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com [110]Dix DB, Fernandez CV, Chi YY, et al. Augmentation of therapy for combined loss of heterozygosity 1p and 16q in favorable histology Wilms tumor: a Children's Oncology Group AREN0532 and AREN0533 study report. J Clin Oncol. 2019 Oct 20;37(30):2769-77. https://ascopubs.org/doi/10.1200/JCO.18.01972 http://www.ncbi.nlm.nih.gov/pubmed/31449468?tool=bestpractice.com
See local specialist protocol for dosing guidelines.
Primary options
EE-4A regimen
vincristine
and
dactinomycin
OR
DD-4A regimen
vincristine
and
dactinomycin
and
doxorubicin
surgery
Upfront nephrectomy using a transperitoneal approach is recommended for patients with unilateral renal masses who do not have a known Wilms' tumour predisposition.[4]Spreafico F, Fernandez CV, Brok J, et al. Wilms tumour. Nat Rev Dis Primers. 2021 Oct 14;7(1):75. https://www.nature.com/articles/s41572-021-00308-8 http://www.ncbi.nlm.nih.gov/pubmed/34650095?tool=bestpractice.com [52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Surgeons should avoid tumour spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]de Campos Vieira Abib S, Chui CH, Cox S, et al. International Society of Paediatric Surgical Oncology (IPSO) surgical practice guidelines. Ecancermedicalscience. 2022 Feb 17;16:1356. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023308 http://www.ncbi.nlm.nih.gov/pubmed/35510137?tool=bestpractice.com
Palpation of renal vein and inferior vena cava identifies any tumour thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Suspicious metastatic lesions (hepatic or intra-abdominal) may be biopsied or resected at the time of initial surgery for diagnostic or therapeutic purposes. Decisions about extrapulmonary metastatic lesions are highly individualised.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com [106]Benedetti DJ, Varela CR, Renfro LA, et al. Treatment of children with favorable histology Wilms tumor with extrapulmonary metastases: a report from the COG studies AREN0533 and AREN03B2 and NWTSG study NWTS-5. Cancer. 2024 Mar 15;130(6):947-61. https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35099 http://www.ncbi.nlm.nih.gov/pubmed/37933882?tool=bestpractice.com
post-operative chemotherapy
Treatment recommended for ALL patients in selected patient group
Favourable histology Wilms' tumours are subdivided by the Children's Oncology Group (COG) into recurrence risk categories (based on patient age, tumour weight, stage, molecular markers, and biological factors), which determine post-operative treatment.[95]Nelson MV, van den Heuvel-Eibrink MM, Graf N, et al. New approaches to risk stratification for Wilms tumor. Curr Opin Pediatr. 2021 Feb 1;33(1):40-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919941 http://www.ncbi.nlm.nih.gov/pubmed/33394739?tool=bestpractice.com [96]Dome JS, Fernandez CV, Mullen EA, et al. Children's Oncology Group's 2013 blueprint for research: renal tumors. Pediatr Blood Cancer. 2013 Jun;60(6):994-1000. http://www.ncbi.nlm.nih.gov/pubmed/23255438?tool=bestpractice.com
Chemotherapy regimen for stage III disease depends on the biology of the tumour.
COG standard-risk patients (stage III, with no loss of heterozygosity [LOH] at combined 1p and 16q): post-operative chemotherapy with vincristine, dactinomycin, and doxorubicin (DD-4A regimen).[109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com [110]Dix DB, Fernandez CV, Chi YY, et al. Augmentation of therapy for combined loss of heterozygosity 1p and 16q in favorable histology Wilms tumor: a Children's Oncology Group AREN0532 and AREN0533 study report. J Clin Oncol. 2019 Oct 20;37(30):2769-77. https://ascopubs.org/doi/10.1200/JCO.18.01972 http://www.ncbi.nlm.nih.gov/pubmed/31449468?tool=bestpractice.com
COG higher-risk patients (stage III, with LOH at combined 1p and 16q): post-operative chemotherapy with DD-4A regimen for 6 weeks, and then switched to vincristine, dactinomycin, doxorubicin, cyclophosphamide, and etoposide (regimen M).[109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com [110]Dix DB, Fernandez CV, Chi YY, et al. Augmentation of therapy for combined loss of heterozygosity 1p and 16q in favorable histology Wilms tumor: a Children's Oncology Group AREN0532 and AREN0533 study report. J Clin Oncol. 2019 Oct 20;37(30):2769-77. https://ascopubs.org/doi/10.1200/JCO.18.01972 http://www.ncbi.nlm.nih.gov/pubmed/31449468?tool=bestpractice.com
See local specialist protocol for dosing guidelines.
Primary options
DD-4A regimen
vincristine
and
dactinomycin
and
doxorubicin
OR
Regimen M
vincristine
and
dactinomycin
and
doxorubicin
and
cyclophosphamide
and
etoposide
radiotherapy
Treatment recommended for ALL patients in selected patient group
All stage III tumours receive either flank irradiation or whole abdomen irradiation.[109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com [110]Dix DB, Fernandez CV, Chi YY, et al. Augmentation of therapy for combined loss of heterozygosity 1p and 16q in favorable histology Wilms tumor: a Children's Oncology Group AREN0532 and AREN0533 study report. J Clin Oncol. 2019 Oct 20;37(30):2769-77. https://ascopubs.org/doi/10.1200/JCO.18.01972 http://www.ncbi.nlm.nih.gov/pubmed/31449468?tool=bestpractice.com
Radiotherapy (either flank irradiation or whole abdomen irradiation) is used for the regional management of local stage III favourable histology Wilms' tumour.[4]Spreafico F, Fernandez CV, Brok J, et al. Wilms tumour. Nat Rev Dis Primers. 2021 Oct 14;7(1):75. https://www.nature.com/articles/s41572-021-00308-8 http://www.ncbi.nlm.nih.gov/pubmed/34650095?tool=bestpractice.com In most cases, flank radiation is used; whole abdominal radiation is only used in cases with peritoneal seeding, preoperative tumour rupture, or an intraoperative spill that is widespread in the opinion of the operating surgeon.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com [99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com [129]Pater L, Melchior P, Rübe C, et al. Wilms tumor. Pediatr Blood Cancer. 2021 May;68 Suppl 2:e28257. https://onlinelibrary.wiley.com/doi/10.1002/pbc.28257 http://www.ncbi.nlm.nih.gov/pubmed/32893998?tool=bestpractice.com
surgery
Upfront nephrectomy using a transperitoneal approach is recommended for patients with unilateral renal masses who do not have a known Wilms' tumour predisposition.[4]Spreafico F, Fernandez CV, Brok J, et al. Wilms tumour. Nat Rev Dis Primers. 2021 Oct 14;7(1):75. https://www.nature.com/articles/s41572-021-00308-8 http://www.ncbi.nlm.nih.gov/pubmed/34650095?tool=bestpractice.com [52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Surgeons should avoid tumour spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]de Campos Vieira Abib S, Chui CH, Cox S, et al. International Society of Paediatric Surgical Oncology (IPSO) surgical practice guidelines. Ecancermedicalscience. 2022 Feb 17;16:1356. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023308 http://www.ncbi.nlm.nih.gov/pubmed/35510137?tool=bestpractice.com
Palpation of renal vein and inferior vena cava identifies any tumour thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Suspicious metastatic lesions (hepatic or intra-abdominal) may be biopsied or resected at the time of initial surgery for diagnostic or therapeutic purposes. Decisions about extrapulmonary metastatic lesions are highly individualised.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com [106]Benedetti DJ, Varela CR, Renfro LA, et al. Treatment of children with favorable histology Wilms tumor with extrapulmonary metastases: a report from the COG studies AREN0533 and AREN03B2 and NWTSG study NWTS-5. Cancer. 2024 Mar 15;130(6):947-61. https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35099 http://www.ncbi.nlm.nih.gov/pubmed/37933882?tool=bestpractice.com
post-operative chemotherapy
Treatment recommended for ALL patients in selected patient group
Favourable histology Wilms' tumours are subdivided by the Children's Oncology Group (COG) into recurrence risk categories (based on patient age, tumour weight, stage, molecular markers, and biological factors), which determine post-operative treatment.[95]Nelson MV, van den Heuvel-Eibrink MM, Graf N, et al. New approaches to risk stratification for Wilms tumor. Curr Opin Pediatr. 2021 Feb 1;33(1):40-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919941 http://www.ncbi.nlm.nih.gov/pubmed/33394739?tool=bestpractice.com [96]Dome JS, Fernandez CV, Mullen EA, et al. Children's Oncology Group's 2013 blueprint for research: renal tumors. Pediatr Blood Cancer. 2013 Jun;60(6):994-1000. http://www.ncbi.nlm.nih.gov/pubmed/23255438?tool=bestpractice.com
Chemotherapy regimen for stage IV disease depends on the location of metastases and biology of the tumour.
Children's Oncology Group (COG) standard-risk patients (stage IV, with no loss of heterozygosity [LOH] at combined 1p and 16q, and no metastases to sites other than lungs): post-operative chemotherapy with vincristine, dactinomycin, and doxorubicin (DD-4A regimen).[109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com Patients with pulmonary metastases with a complete response at week 6 continue receiving DD-4A without whole lung irradiation.[71]Dix DB, Seibel NL, Chi YY, et al. Treatment of stage IV favorable histology Wilms tumor with lung metastases: a report from the Children's Oncology Group AREN0533 study. J Clin Oncol. 2018 Jun 1;36(16):1564-70. https://ascopubs.org/doi/10.1200/JCO.2017.77.1931 http://www.ncbi.nlm.nih.gov/pubmed/29659330?tool=bestpractice.com However, intensification of chemotherapy and whole lung irradiation can be considered for patients with a 1q gain. Rate of event-free survival is lower for patients with 1q gain receiving standard treatment.[71]Dix DB, Seibel NL, Chi YY, et al. Treatment of stage IV favorable histology Wilms tumor with lung metastases: a report from the Children's Oncology Group AREN0533 study. J Clin Oncol. 2018 Jun 1;36(16):1564-70. https://ascopubs.org/doi/10.1200/JCO.2017.77.1931 http://www.ncbi.nlm.nih.gov/pubmed/29659330?tool=bestpractice.com Patients with an incomplete/slow response of pulmonary metastatic lesions at week 6 are switched to vincristine, dactinomycin, doxorubicin, cyclophosphamide, and etoposide (regimen M) and receive whole lung irradiation.[71]Dix DB, Seibel NL, Chi YY, et al. Treatment of stage IV favorable histology Wilms tumor with lung metastases: a report from the Children's Oncology Group AREN0533 study. J Clin Oncol. 2018 Jun 1;36(16):1564-70. https://ascopubs.org/doi/10.1200/JCO.2017.77.1931 http://www.ncbi.nlm.nih.gov/pubmed/29659330?tool=bestpractice.com
COG higher-risk patients (stage IV, with LOH at combined 1p and 16q, or metastases to site other than lungs): post-operative chemotherapy with DD-4A regimen for 6 weeks, and then switched to regimen M.[109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com [110]Dix DB, Fernandez CV, Chi YY, et al. Augmentation of therapy for combined loss of heterozygosity 1p and 16q in favorable histology Wilms tumor: a Children's Oncology Group AREN0532 and AREN0533 study report. J Clin Oncol. 2019 Oct 20;37(30):2769-77. https://ascopubs.org/doi/10.1200/JCO.18.01972 http://www.ncbi.nlm.nih.gov/pubmed/31449468?tool=bestpractice.com
See local specialist protocol for dosing guidelines.
Primary options
DD-4A regimen
vincristine
and
dactinomycin
and
doxorubicin
OR
Regimen M
vincristine
and
dactinomycin
and
doxorubicin
and
cyclophosphamide
and
etoposide
radiotherapy
Additional treatment recommended for SOME patients in selected patient group
Radiotherapy (either flank irradiation or whole abdomen irradiation) is used for the regional management of local stage III favourable histology Wilms' tumour (staging at primary tumour regardless of metastases).[4]Spreafico F, Fernandez CV, Brok J, et al. Wilms tumour. Nat Rev Dis Primers. 2021 Oct 14;7(1):75. https://www.nature.com/articles/s41572-021-00308-8 http://www.ncbi.nlm.nih.gov/pubmed/34650095?tool=bestpractice.com In most cases, flank radiation is used; whole abdominal radiation is only used in cases with peritoneal seeding, preoperative tumour rupture, or an intraoperative spill that is widespread in the opinion of the operating surgeon.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com [99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com [129]Pater L, Melchior P, Rübe C, et al. Wilms tumor. Pediatr Blood Cancer. 2021 May;68 Suppl 2:e28257. https://onlinelibrary.wiley.com/doi/10.1002/pbc.28257 http://www.ncbi.nlm.nih.gov/pubmed/32893998?tool=bestpractice.com
The Children's Oncology Group (COG) standard-risk patients: abdominal/flank irradiation is given to patients with local/abdominal stage III disease. Patients with pulmonary metastases with an incomplete/slow response of pulmonary metastatic lesions at week 6 of chemotherapy receive whole lung irradiation.[71]Dix DB, Seibel NL, Chi YY, et al. Treatment of stage IV favorable histology Wilms tumor with lung metastases: a report from the Children's Oncology Group AREN0533 study. J Clin Oncol. 2018 Jun 1;36(16):1564-70. https://ascopubs.org/doi/10.1200/JCO.2017.77.1931 http://www.ncbi.nlm.nih.gov/pubmed/29659330?tool=bestpractice.com [109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com
Standard-risk patients with pulmonary metastases with a complete response at week 6 continue chemotherapy without whole lung irradiation.[71]Dix DB, Seibel NL, Chi YY, et al. Treatment of stage IV favorable histology Wilms tumor with lung metastases: a report from the Children's Oncology Group AREN0533 study. J Clin Oncol. 2018 Jun 1;36(16):1564-70. https://ascopubs.org/doi/10.1200/JCO.2017.77.1931 http://www.ncbi.nlm.nih.gov/pubmed/29659330?tool=bestpractice.com However, intensification of chemotherapy and whole lung irradiation can be considered for patients with a 1q gain. Rate of event-free survival is lower for patients with 1q gain receiving standard treatment.[71]Dix DB, Seibel NL, Chi YY, et al. Treatment of stage IV favorable histology Wilms tumor with lung metastases: a report from the Children's Oncology Group AREN0533 study. J Clin Oncol. 2018 Jun 1;36(16):1564-70. https://ascopubs.org/doi/10.1200/JCO.2017.77.1931 http://www.ncbi.nlm.nih.gov/pubmed/29659330?tool=bestpractice.com
COG higher-risk patients: abdominal/flank irradiation is given to patients with local/abdominal stage III disease. Patients receive whole lung irradiation or radiation to non-lung metastatic sites.[109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com [110]Dix DB, Fernandez CV, Chi YY, et al. Augmentation of therapy for combined loss of heterozygosity 1p and 16q in favorable histology Wilms tumor: a Children's Oncology Group AREN0532 and AREN0533 study report. J Clin Oncol. 2019 Oct 20;37(30):2769-77. https://ascopubs.org/doi/10.1200/JCO.18.01972 http://www.ncbi.nlm.nih.gov/pubmed/31449468?tool=bestpractice.com
Treatment of extrapulmonary metastatic lesions is highly individualised.[106]Benedetti DJ, Varela CR, Renfro LA, et al. Treatment of children with favorable histology Wilms tumor with extrapulmonary metastases: a report from the COG studies AREN0533 and AREN03B2 and NWTSG study NWTS-5. Cancer. 2024 Mar 15;130(6):947-61. https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35099 http://www.ncbi.nlm.nih.gov/pubmed/37933882?tool=bestpractice.com
preoperative chemotherapy
Patients who cannot undergo upfront nephrectomy have a tumour biopsy performed, followed by neoadjuvant chemotherapy until delayed nephrectomy. Chemotherapy is then completed post-operatively.
The Children's Oncology Group (COG) recommends upfront biopsy and preoperative chemotherapy if the tumour extends into inferior vena cava above the hepatic vein or the primary tumour is unresectable at presentation.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
If a tumour is unresectable, COG recommends an open biopsy or core needle biopsy with a minimum of 10-12 non-necrotic cores to ensure sufficient tissue for molecular testing. Performing a tumour biopsy results in upstaging to local stage III disease.[4]Spreafico F, Fernandez CV, Brok J, et al. Wilms tumour. Nat Rev Dis Primers. 2021 Oct 14;7(1):75. https://www.nature.com/articles/s41572-021-00308-8 http://www.ncbi.nlm.nih.gov/pubmed/34650095?tool=bestpractice.com [52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Preoperative chemotherapy is used to reduce the size of the tumour. For COG standard-risk patients, vincristine, dactinomycin, and doxorubicin (DD-4A regimen) is given until delayed nephrectomy. Higher-risk patients are given DD-4A regimen for 6 weeks and then switched to vincristine, dactinomycin, doxorubicin, cyclophosphamide, and etoposide (regimen M) until delayed nephrectomy.
See local specialist protocol for dosing guidelines.
Primary options
DD-4A regimen
vincristine
and
dactinomycin
and
doxorubicin
OR
Regimen M
vincristine
and
dactinomycin
and
doxorubicin
and
cyclophosphamide
and
etoposide
surgery
Treatment recommended for ALL patients in selected patient group
Delayed nephrectomy using a transperitoneal approach is recommended following preoperative chemotherapy for patients with unresectable, favourable histology tumours.[4]Spreafico F, Fernandez CV, Brok J, et al. Wilms tumour. Nat Rev Dis Primers. 2021 Oct 14;7(1):75. https://www.nature.com/articles/s41572-021-00308-8 http://www.ncbi.nlm.nih.gov/pubmed/34650095?tool=bestpractice.com [52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Surgeons should avoid tumour spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]de Campos Vieira Abib S, Chui CH, Cox S, et al. International Society of Paediatric Surgical Oncology (IPSO) surgical practice guidelines. Ecancermedicalscience. 2022 Feb 17;16:1356. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023308 http://www.ncbi.nlm.nih.gov/pubmed/35510137?tool=bestpractice.com
Palpation of renal vein and inferior vena cava identifies any tumour thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Suspicious metastatic lesions (hepatic or intra-abdominal) may be biopsied or resected at the time of initial surgery for diagnostic or therapeutic purposes. Decisions about extrapulmonary metastatic lesions are highly individualised.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com [106]Benedetti DJ, Varela CR, Renfro LA, et al. Treatment of children with favorable histology Wilms tumor with extrapulmonary metastases: a report from the COG studies AREN0533 and AREN03B2 and NWTSG study NWTS-5. Cancer. 2024 Mar 15;130(6):947-61. https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35099 http://www.ncbi.nlm.nih.gov/pubmed/37933882?tool=bestpractice.com
post-operative chemotherapy
Treatment recommended for ALL patients in selected patient group
Post-operative chemotherapy is recommended to complete the initial preoperative chemotherapy regimen, either with vincristine, dactinomycin, and doxorubicin (DD-4A regimen) or vincristine, dactinomycin, doxorubicin, cyclophosphamide, and etoposide (regimen M).
See local specialist protocol for dosing guidelines.
Primary options
DD-4A regimen
vincristine
and
dactinomycin
and
doxorubicin
OR
Regimen M
vincristine
and
dactinomycin
and
doxorubicin
and
cyclophosphamide
and
etoposide
radiotherapy
Treatment recommended for ALL patients in selected patient group
Radiotherapy (either flank irradiation or whole abdomen irradiation) is used for the regional management of local stage III favourable histology Wilms' tumour (staging at primary tumour regardless of metastases).[4]Spreafico F, Fernandez CV, Brok J, et al. Wilms tumour. Nat Rev Dis Primers. 2021 Oct 14;7(1):75. https://www.nature.com/articles/s41572-021-00308-8 http://www.ncbi.nlm.nih.gov/pubmed/34650095?tool=bestpractice.com In most cases, flank radiation is used; whole abdominal radiation is only used in cases with peritoneal seeding, preoperative tumour rupture, or an intraoperative spill that is widespread in the opinion of the operating surgeon.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com [99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com [129]Pater L, Melchior P, Rübe C, et al. Wilms tumor. Pediatr Blood Cancer. 2021 May;68 Suppl 2:e28257. https://onlinelibrary.wiley.com/doi/10.1002/pbc.28257 http://www.ncbi.nlm.nih.gov/pubmed/32893998?tool=bestpractice.com
Stage IV standard-risk patients with pulmonary metastases who do not show complete response to chemotherapy at week 6 receive whole lung irradiation.[71]Dix DB, Seibel NL, Chi YY, et al. Treatment of stage IV favorable histology Wilms tumor with lung metastases: a report from the Children's Oncology Group AREN0533 study. J Clin Oncol. 2018 Jun 1;36(16):1564-70. https://ascopubs.org/doi/10.1200/JCO.2017.77.1931 http://www.ncbi.nlm.nih.gov/pubmed/29659330?tool=bestpractice.com
Stage IV higher-risk patients receive whole lung irradiation or radiotherapy to non-lung sites of metastasis.[109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com [110]Dix DB, Fernandez CV, Chi YY, et al. Augmentation of therapy for combined loss of heterozygosity 1p and 16q in favorable histology Wilms tumor: a Children's Oncology Group AREN0532 and AREN0533 study report. J Clin Oncol. 2019 Oct 20;37(30):2769-77. https://ascopubs.org/doi/10.1200/JCO.18.01972 http://www.ncbi.nlm.nih.gov/pubmed/31449468?tool=bestpractice.com Treatment of extrapulmonary metastatic lesions is highly individualised.[106]Benedetti DJ, Varela CR, Renfro LA, et al. Treatment of children with favorable histology Wilms tumor with extrapulmonary metastases: a report from the COG studies AREN0533 and AREN03B2 and NWTSG study NWTS-5. Cancer. 2024 Mar 15;130(6):947-61. https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35099 http://www.ncbi.nlm.nih.gov/pubmed/37933882?tool=bestpractice.com
preoperative chemotherapy
In patients with bilateral Wilms' tumour or bilaterally predisposed unilateral Wilms' tumour, preoperative chemotherapy is followed by nephron-sparing surgery and modified post-operative chemotherapy based on histological response.[97]Ehrlich PF, Chi YY, Chintagumpala MM, et al. Results of treatment for patients with multicentric or bilaterally predisposed unilateral Wilms tumor (AREN0534): a report from the Children's Oncology Group. Cancer. 2020 Aug 1;126(15):3516-25. https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.32958 http://www.ncbi.nlm.nih.gov/pubmed/32459384?tool=bestpractice.com [109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com [113]Ehrlich P, Chi YY, Chintagumpala MM, et al. Results of the first prospective multi-institutional treatment study in children with bilateral Wilms tumor (AREN0534): a report from the Children's Oncology Group. Ann Surg. 2017 Sep;266(3):470-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629006 http://www.ncbi.nlm.nih.gov/pubmed/28795993?tool=bestpractice.com
The goal of preoperative chemotherapy is to shrink the tumour to allow maximum preservation of renal parenchyma.[97]Ehrlich PF, Chi YY, Chintagumpala MM, et al. Results of treatment for patients with multicentric or bilaterally predisposed unilateral Wilms tumor (AREN0534): a report from the Children's Oncology Group. Cancer. 2020 Aug 1;126(15):3516-25. https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.32958 http://www.ncbi.nlm.nih.gov/pubmed/32459384?tool=bestpractice.com
For patients with bilateral Wilms' tumour, or with bilaterally predisposed unilateral Wilms' tumour with metastatic disease: vincristine, dactinomycin, and doxorubicin (VAD regimen) are given preoperatively.[113]Ehrlich P, Chi YY, Chintagumpala MM, et al. Results of the first prospective multi-institutional treatment study in children with bilateral Wilms tumor (AREN0534): a report from the Children's Oncology Group. Ann Surg. 2017 Sep;266(3):470-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629006 http://www.ncbi.nlm.nih.gov/pubmed/28795993?tool=bestpractice.com
For patients with bilaterally predisposed unilateral Wilms' tumour that is localised (no metastatic disease): vincristine and dactinomycin (VA regimen) are used preoperatively.[113]Ehrlich P, Chi YY, Chintagumpala MM, et al. Results of the first prospective multi-institutional treatment study in children with bilateral Wilms tumor (AREN0534): a report from the Children's Oncology Group. Ann Surg. 2017 Sep;266(3):470-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629006 http://www.ncbi.nlm.nih.gov/pubmed/28795993?tool=bestpractice.com
See local specialist protocol for dosing guidelines.
Primary options
VAD regimen
vincristine
and
dactinomycin
and
doxorubicin
OR
VA regimen
vincristine
and
dactinomycin
surgery
Treatment recommended for ALL patients in selected patient group
Radical nephrectomies can potentially be avoided and nephron-sparing surgery used to preserve renal parenchyma and function.[113]Ehrlich P, Chi YY, Chintagumpala MM, et al. Results of the first prospective multi-institutional treatment study in children with bilateral Wilms tumor (AREN0534): a report from the Children's Oncology Group. Ann Surg. 2017 Sep;266(3):470-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629006 http://www.ncbi.nlm.nih.gov/pubmed/28795993?tool=bestpractice.com
post-operative chemotherapy
Treatment recommended for ALL patients in selected patient group
Post-operative chemotherapy is based on stage and histological response.[97]Ehrlich PF, Chi YY, Chintagumpala MM, et al. Results of treatment for patients with multicentric or bilaterally predisposed unilateral Wilms tumor (AREN0534): a report from the Children's Oncology Group. Cancer. 2020 Aug 1;126(15):3516-25. https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.32958 http://www.ncbi.nlm.nih.gov/pubmed/32459384?tool=bestpractice.com [109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com [113]Ehrlich P, Chi YY, Chintagumpala MM, et al. Results of the first prospective multi-institutional treatment study in children with bilateral Wilms tumor (AREN0534): a report from the Children's Oncology Group. Ann Surg. 2017 Sep;266(3):470-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629006 http://www.ncbi.nlm.nih.gov/pubmed/28795993?tool=bestpractice.com
Each kidney should be individually staged and treated accordingly.
See local specialist protocol for regimen and dosing guidelines.
renal transplant
Additional treatment recommended for SOME patients in selected patient group
Rarely, disease is extensive bilaterally requiring bilateral complete nephrectomies and resulting in renal failure and need for a renal transplant.[114]Aronson DC, Slaar A, Heinen RC, et al. Long-term outcome of bilateral Wilms tumors (BWT). Pediatr Blood Cancer. 2011 Jul 1;56(7):1110-3. http://www.ncbi.nlm.nih.gov/pubmed/21370428?tool=bestpractice.com
surgery
Upfront nephrectomy using a transperitoneal approach is recommended for patients with unilateral renal masses who do not have a known Wilms' tumour predisposition.[4]Spreafico F, Fernandez CV, Brok J, et al. Wilms tumour. Nat Rev Dis Primers. 2021 Oct 14;7(1):75. https://www.nature.com/articles/s41572-021-00308-8 http://www.ncbi.nlm.nih.gov/pubmed/34650095?tool=bestpractice.com [52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Surgeons should avoid tumour spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]de Campos Vieira Abib S, Chui CH, Cox S, et al. International Society of Paediatric Surgical Oncology (IPSO) surgical practice guidelines. Ecancermedicalscience. 2022 Feb 17;16:1356. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023308 http://www.ncbi.nlm.nih.gov/pubmed/35510137?tool=bestpractice.com
Palpation of renal vein and inferior vena cava identifies any tumour thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Suspicious metastatic lesions (hepatic or intra-abdominal) may be biopsied or resected at the time of initial surgery for diagnostic or therapeutic purposes. Decisions about extrapulmonary metastatic lesions are highly individualised.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
post-operative chemotherapy
Treatment recommended for ALL patients in selected patient group
Stage I patients with either focal or diffuse anaplasia receive post-operative chemotherapy with vincristine, dactinomycin, and doxorubicin (DD-4A regimen).[115]Daw NC, Chi YY, Kim Y, et al. Treatment of stage I anaplastic Wilms' tumour: a report from the Children's Oncology Group AREN0321 study. Eur J Cancer. 2019 Sep;118:58-66. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690766 http://www.ncbi.nlm.nih.gov/pubmed/31325873?tool=bestpractice.com [116]Armstrong AE, Daw NC, Renfro LA, et al. Treatment of focal anaplastic Wilms tumor: a report from the Children's Oncology Group AREN0321 and AREN03B2 studies. Cancer. 2025 Jan 15;131(2):e35713. http://www.ncbi.nlm.nih.gov/pubmed/39803937?tool=bestpractice.com
See local specialist protocol for dosing guidelines.
Primary options
DD-4A regimen
vincristine
and
dactinomycin
and
doxorubicin
radiotherapy
Treatment recommended for ALL patients in selected patient group
Stage I patients with either focal or diffuse anaplasia receive flank irradiation.[115]Daw NC, Chi YY, Kim Y, et al. Treatment of stage I anaplastic Wilms' tumour: a report from the Children's Oncology Group AREN0321 study. Eur J Cancer. 2019 Sep;118:58-66. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690766 http://www.ncbi.nlm.nih.gov/pubmed/31325873?tool=bestpractice.com [116]Armstrong AE, Daw NC, Renfro LA, et al. Treatment of focal anaplastic Wilms tumor: a report from the Children's Oncology Group AREN0321 and AREN03B2 studies. Cancer. 2025 Jan 15;131(2):e35713. http://www.ncbi.nlm.nih.gov/pubmed/39803937?tool=bestpractice.com
surgery
Upfront nephrectomy using a transperitoneal approach is recommended for patients with unilateral renal masses who do not have a known Wilms' tumour predisposition.[4]Spreafico F, Fernandez CV, Brok J, et al. Wilms tumour. Nat Rev Dis Primers. 2021 Oct 14;7(1):75. https://www.nature.com/articles/s41572-021-00308-8 http://www.ncbi.nlm.nih.gov/pubmed/34650095?tool=bestpractice.com [52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Surgeons should avoid tumour spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]de Campos Vieira Abib S, Chui CH, Cox S, et al. International Society of Paediatric Surgical Oncology (IPSO) surgical practice guidelines. Ecancermedicalscience. 2022 Feb 17;16:1356. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023308 http://www.ncbi.nlm.nih.gov/pubmed/35510137?tool=bestpractice.com
Palpation of renal vein and inferior vena cava identifies any tumour thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Suspicious metastatic lesions (hepatic or intra-abdominal) may be biopsied or resected at the time of initial surgery for diagnostic or therapeutic purposes. Decisions about extrapulmonary metastatic lesions are highly individualised.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
post-operative chemotherapy
Treatment recommended for ALL patients in selected patient group
Treatment regimen depends on whether anaplasia is focal or diffuse.
Focal anaplasia: post-operative chemotherapy with vincristine, dactinomycin, and doxorubicin (DD-4A regimen).[116]Armstrong AE, Daw NC, Renfro LA, et al. Treatment of focal anaplastic Wilms tumor: a report from the Children's Oncology Group AREN0321 and AREN03B2 studies. Cancer. 2025 Jan 15;131(2):e35713. http://www.ncbi.nlm.nih.gov/pubmed/39803937?tool=bestpractice.com [117]Dome JS, Cotton CA, Perlman EJ, et al. Treatment of anaplastic histology Wilms' tumor: results from the fifth National Wilms' Tumor Study. J Clin Oncol. 2006 May 20;24(15):2352-8. http://www.ncbi.nlm.nih.gov/pubmed/16710034?tool=bestpractice.com
Diffuse anaplasia: post-operative chemotherapy with vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan (revised UH-2 regimen).[109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com [118]Daw NC, Chi YY, Kalapurakal JA, et al. Activity of vincristine and irinotecan in diffuse anaplastic Wilms tumor and therapy outcomes of stage II to IV disease: results of the Children's Oncology Group AREN0321 study. J Clin Oncol. 2020 May 10;38(14):1558-68. https://ascopubs.org/doi/10.1200/JCO.19.01265 http://www.ncbi.nlm.nih.gov/pubmed/32134700?tool=bestpractice.com
See local specialist protocol for dosing guidelines.
Primary options
DD-4A regimen
vincristine
and
dactinomycin
and
doxorubicin
OR
revised UH-2 regimen
vincristine
and
doxorubicin
and
cyclophosphamide
and
carboplatin
and
etoposide
and
irinotecan
radiotherapy
Treatment recommended for ALL patients in selected patient group
Patients with focal or diffuse anaplasia should receive flank irradiation.[109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com [116]Armstrong AE, Daw NC, Renfro LA, et al. Treatment of focal anaplastic Wilms tumor: a report from the Children's Oncology Group AREN0321 and AREN03B2 studies. Cancer. 2025 Jan 15;131(2):e35713. http://www.ncbi.nlm.nih.gov/pubmed/39803937?tool=bestpractice.com [117]Dome JS, Cotton CA, Perlman EJ, et al. Treatment of anaplastic histology Wilms' tumor: results from the fifth National Wilms' Tumor Study. J Clin Oncol. 2006 May 20;24(15):2352-8. http://www.ncbi.nlm.nih.gov/pubmed/16710034?tool=bestpractice.com
surgery
Upfront nephrectomy using a transperitoneal approach is recommended for patients with unilateral renal masses who do not have a known Wilms' tumour predisposition.[4]Spreafico F, Fernandez CV, Brok J, et al. Wilms tumour. Nat Rev Dis Primers. 2021 Oct 14;7(1):75. https://www.nature.com/articles/s41572-021-00308-8 http://www.ncbi.nlm.nih.gov/pubmed/34650095?tool=bestpractice.com [52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Surgeons should avoid tumour spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]de Campos Vieira Abib S, Chui CH, Cox S, et al. International Society of Paediatric Surgical Oncology (IPSO) surgical practice guidelines. Ecancermedicalscience. 2022 Feb 17;16:1356. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023308 http://www.ncbi.nlm.nih.gov/pubmed/35510137?tool=bestpractice.com
Palpation of renal vein and inferior vena cava identifies any tumour thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Suspicious metastatic lesions (hepatic or intra-abdominal) may be biopsied or resected at the time of initial surgery for diagnostic or therapeutic purposes. Decisions about extrapulmonary metastatic lesions are highly individualised.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
post-operative chemotherapy
Treatment recommended for ALL patients in selected patient group
Treatment regimen depends on whether anaplasia is focal or diffuse.
Focal anaplasia: post-operative chemotherapy with vincristine, dactinomycin, and doxorubicin (DD-4A regimen).[116]Armstrong AE, Daw NC, Renfro LA, et al. Treatment of focal anaplastic Wilms tumor: a report from the Children's Oncology Group AREN0321 and AREN03B2 studies. Cancer. 2025 Jan 15;131(2):e35713. http://www.ncbi.nlm.nih.gov/pubmed/39803937?tool=bestpractice.com [117]Dome JS, Cotton CA, Perlman EJ, et al. Treatment of anaplastic histology Wilms' tumor: results from the fifth National Wilms' Tumor Study. J Clin Oncol. 2006 May 20;24(15):2352-8. http://www.ncbi.nlm.nih.gov/pubmed/16710034?tool=bestpractice.com
Diffuse anaplasia: post-operative chemotherapy with vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan (revised UH-2 regimen).[109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com [118]Daw NC, Chi YY, Kalapurakal JA, et al. Activity of vincristine and irinotecan in diffuse anaplastic Wilms tumor and therapy outcomes of stage II to IV disease: results of the Children's Oncology Group AREN0321 study. J Clin Oncol. 2020 May 10;38(14):1558-68. https://ascopubs.org/doi/10.1200/JCO.19.01265 http://www.ncbi.nlm.nih.gov/pubmed/32134700?tool=bestpractice.com
See local specialist protocol for dosing guidelines.
Primary options
DD-4A regimen
vincristine
and
dactinomycin
and
doxorubicin
OR
revised UH-2 regimen
vincristine
and
doxorubicin
and
cyclophosphamide
and
carboplatin
and
etoposide
and
irinotecan
radiotherapy
Treatment recommended for ALL patients in selected patient group
Patients with focal or diffuse anaplasia should receive abdomen/flank irradiation, with a boost to residual tumour.[109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com [116]Armstrong AE, Daw NC, Renfro LA, et al. Treatment of focal anaplastic Wilms tumor: a report from the Children's Oncology Group AREN0321 and AREN03B2 studies. Cancer. 2025 Jan 15;131(2):e35713. http://www.ncbi.nlm.nih.gov/pubmed/39803937?tool=bestpractice.com [117]Dome JS, Cotton CA, Perlman EJ, et al. Treatment of anaplastic histology Wilms' tumor: results from the fifth National Wilms' Tumor Study. J Clin Oncol. 2006 May 20;24(15):2352-8. http://www.ncbi.nlm.nih.gov/pubmed/16710034?tool=bestpractice.com
surgery
Upfront nephrectomy using a transperitoneal approach is recommended for patients with unilateral renal masses who do not have a known Wilms' tumour predisposition.[4]Spreafico F, Fernandez CV, Brok J, et al. Wilms tumour. Nat Rev Dis Primers. 2021 Oct 14;7(1):75. https://www.nature.com/articles/s41572-021-00308-8 http://www.ncbi.nlm.nih.gov/pubmed/34650095?tool=bestpractice.com [52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Surgeons should avoid tumour spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]de Campos Vieira Abib S, Chui CH, Cox S, et al. International Society of Paediatric Surgical Oncology (IPSO) surgical practice guidelines. Ecancermedicalscience. 2022 Feb 17;16:1356. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023308 http://www.ncbi.nlm.nih.gov/pubmed/35510137?tool=bestpractice.com
Palpation of renal vein and inferior vena cava identifies any tumour thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Suspicious metastatic lesions (hepatic or intra-abdominal) may be biopsied or resected at the time of initial surgery for diagnostic or therapeutic purposes. Decisions about extrapulmonary metastatic lesions are highly individualised.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
post-operative chemotherapy
Treatment recommended for ALL patients in selected patient group
Treatment regimen depends on whether anaplasia is focal or diffuse.
Focal anaplasia: post-operative chemotherapy with vincristine, doxorubicin, cyclophosphamide, carboplatin, and etoposide (revised UH-1 regimen).[116]Armstrong AE, Daw NC, Renfro LA, et al. Treatment of focal anaplastic Wilms tumor: a report from the Children's Oncology Group AREN0321 and AREN03B2 studies. Cancer. 2025 Jan 15;131(2):e35713. http://www.ncbi.nlm.nih.gov/pubmed/39803937?tool=bestpractice.com [117]Dome JS, Cotton CA, Perlman EJ, et al. Treatment of anaplastic histology Wilms' tumor: results from the fifth National Wilms' Tumor Study. J Clin Oncol. 2006 May 20;24(15):2352-8. http://www.ncbi.nlm.nih.gov/pubmed/16710034?tool=bestpractice.com
Diffuse anaplasia: vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan (revised UH-2 regimen).[109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com [118]Daw NC, Chi YY, Kalapurakal JA, et al. Activity of vincristine and irinotecan in diffuse anaplastic Wilms tumor and therapy outcomes of stage II to IV disease: results of the Children's Oncology Group AREN0321 study. J Clin Oncol. 2020 May 10;38(14):1558-68. https://ascopubs.org/doi/10.1200/JCO.19.01265 http://www.ncbi.nlm.nih.gov/pubmed/32134700?tool=bestpractice.com
See local specialist protocol for dosing guidelines.
Primary options
revised UH-1 regimen
vincristine
and
doxorubicin
and
cyclophosphamide
and
carboplatin
and
etoposide
OR
revised UH-2 regimen
vincristine
and
doxorubicin
and
cyclophosphamide
and
carboplatin
and
etoposide
and
irinotecan
radiotherapy
Treatment recommended for ALL patients in selected patient group
Patients with either focal or diffuse anaplasia receive abdomen/flank irradiation, with a boost to residual tumour.[109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com [117]Dome JS, Cotton CA, Perlman EJ, et al. Treatment of anaplastic histology Wilms' tumor: results from the fifth National Wilms' Tumor Study. J Clin Oncol. 2006 May 20;24(15):2352-8. http://www.ncbi.nlm.nih.gov/pubmed/16710034?tool=bestpractice.com Radiotherapy is given to metastatic sites.
preoperative chemotherapy
In patients with bilateral Wilms' tumour or bilaterally predisposed unilateral Wilms' tumour, preoperative chemotherapy is followed by nephron-sparing surgery and modified post-operative chemotherapy based on histological response.[97]Ehrlich PF, Chi YY, Chintagumpala MM, et al. Results of treatment for patients with multicentric or bilaterally predisposed unilateral Wilms tumor (AREN0534): a report from the Children's Oncology Group. Cancer. 2020 Aug 1;126(15):3516-25. https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.32958 http://www.ncbi.nlm.nih.gov/pubmed/32459384?tool=bestpractice.com [109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com [113]Ehrlich P, Chi YY, Chintagumpala MM, et al. Results of the first prospective multi-institutional treatment study in children with bilateral Wilms tumor (AREN0534): a report from the Children's Oncology Group. Ann Surg. 2017 Sep;266(3):470-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629006 http://www.ncbi.nlm.nih.gov/pubmed/28795993?tool=bestpractice.com
The goal of preoperative chemotherapy is to shrink the tumour to allow maximum preservation of renal parenchyma.[97]Ehrlich PF, Chi YY, Chintagumpala MM, et al. Results of treatment for patients with multicentric or bilaterally predisposed unilateral Wilms tumor (AREN0534): a report from the Children's Oncology Group. Cancer. 2020 Aug 1;126(15):3516-25. https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.32958 http://www.ncbi.nlm.nih.gov/pubmed/32459384?tool=bestpractice.com
For patients with bilateral Wilms' tumour, or with bilaterally predisposed unilateral Wilms' tumour with metastatic disease: vincristine, dactinomycin, and doxorubicin (VAD regimen) is used preoperatively.[113]Ehrlich P, Chi YY, Chintagumpala MM, et al. Results of the first prospective multi-institutional treatment study in children with bilateral Wilms tumor (AREN0534): a report from the Children's Oncology Group. Ann Surg. 2017 Sep;266(3):470-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629006 http://www.ncbi.nlm.nih.gov/pubmed/28795993?tool=bestpractice.com
For patients with bilaterally predisposed unilateral Wilms' tumour that is localised (no metastatic disease): vincristine and dactinomycin (VA regimen) is used preoperatively.[113]Ehrlich P, Chi YY, Chintagumpala MM, et al. Results of the first prospective multi-institutional treatment study in children with bilateral Wilms tumor (AREN0534): a report from the Children's Oncology Group. Ann Surg. 2017 Sep;266(3):470-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629006 http://www.ncbi.nlm.nih.gov/pubmed/28795993?tool=bestpractice.com
See local specialist protocol for dosing guidelines.
Primary options
VAD regimen
vincristine
and
dactinomycin
and
doxorubicin
OR
VA regimen
vincristine
and
dactinomycin
surgery
Treatment recommended for ALL patients in selected patient group
Radical nephrectomies can potentially be avoided and nephron-sparing surgery used to preserve renal parenchyma and function.[113]Ehrlich P, Chi YY, Chintagumpala MM, et al. Results of the first prospective multi-institutional treatment study in children with bilateral Wilms tumor (AREN0534): a report from the Children's Oncology Group. Ann Surg. 2017 Sep;266(3):470-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629006 http://www.ncbi.nlm.nih.gov/pubmed/28795993?tool=bestpractice.com
post-operative chemotherapy
Treatment recommended for ALL patients in selected patient group
Post-operative chemotherapy is based on stage and histological response.[97]Ehrlich PF, Chi YY, Chintagumpala MM, et al. Results of treatment for patients with multicentric or bilaterally predisposed unilateral Wilms tumor (AREN0534): a report from the Children's Oncology Group. Cancer. 2020 Aug 1;126(15):3516-25. https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.32958 http://www.ncbi.nlm.nih.gov/pubmed/32459384?tool=bestpractice.com [113]Ehrlich P, Chi YY, Chintagumpala MM, et al. Results of the first prospective multi-institutional treatment study in children with bilateral Wilms tumor (AREN0534): a report from the Children's Oncology Group. Ann Surg. 2017 Sep;266(3):470-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629006 http://www.ncbi.nlm.nih.gov/pubmed/28795993?tool=bestpractice.com [109]Dome JS, Mullen EA, Dix DB, et al. Impact of the first generation of Children's Oncology Group clinical trials on clinical practice for Wilms tumor. J Natl Compr Canc Netw. 2021 Aug 1;19(8):978-85. https://jnccn.org/view/journals/jnccn/19/8/article-p978.xml http://www.ncbi.nlm.nih.gov/pubmed/34416705?tool=bestpractice.com
Each kidney should be staged individually and treated accordingly.
See local specialist protocol for dosing guidelines.
renal transplant
Additional treatment recommended for SOME patients in selected patient group
Rarely, disease is extensive bilaterally, requiring bilateral complete nephrectomies and resulting in renal failure and need for a renal transplant.[114]Aronson DC, Slaar A, Heinen RC, et al. Long-term outcome of bilateral Wilms tumors (BWT). Pediatr Blood Cancer. 2011 Jul 1;56(7):1110-3. http://www.ncbi.nlm.nih.gov/pubmed/21370428?tool=bestpractice.com
SIOP criteria
preoperative chemotherapy
The UMBRELLA International Society of Paediatric Oncology (SIOP)-Renal Tumour Study Group (RTSG) 2016 protocol (known as the UMBRELLA protocol) recommends upfront chemotherapy for patients aged ≥6 months newly diagnosed with Wilms' tumour (prior to any attempt at resection regardless of initial stage).[73]Vujanić GM, Parsons LN, D'Hooghe E, et al. Pathology of Wilms' tumour in International Society of Paediatric Oncology (SIOP) and Children's Oncology Group (COG) renal tumour studies: similarities and differences. Histopathology. 2022 Jun;80(7):1026-37. http://www.ncbi.nlm.nih.gov/pubmed/35275409?tool=bestpractice.com [99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com
For children <6 months, the UMBRELLA protocol recommends upfront surgery and consideration of fine-needle biopsy for patients with unusual clinical presentations, or unusual findings on imaging, to decrease the risk of misdiagnosis of Wilms' tumour.[99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com [119]Jackson TJ, Brisse HJ, Pritchard-Jones K, et al. How we approach paediatric renal tumour core needle biopsy in the setting of preoperative chemotherapy: a review from the SIOP Renal Tumour Study Group. Pediatr Blood Cancer. 2022 Sep;69(9):e29702. https://onlinelibrary.wiley.com/doi/10.1002/pbc.29702 http://www.ncbi.nlm.nih.gov/pubmed/35587187?tool=bestpractice.com
SIOP any risk: preoperative chemotherapy with dactinomycin and vincristine (AV regimen) for 4 weeks.
See local specialist protocol for dosing guidelines.
Primary options
AV regimen
dactinomycin
and
vincristine
surgery
Treatment recommended for ALL patients in selected patient group
After preoperative chemotherapy in patients aged ≥6 months, radical tumour nephrectomy is the standard of care.[99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com
The UMBRELLA protocol specifies that nephron-sparing surgery is acceptable for the following patients with non-syndromic unilateral Wilms' tumours: small tumour volume (<300 mL) and the expectation of a substantial remnant kidney function in patients with tumours <300 mL who never had lymph node involvement.[99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com
Surgeons should avoid tumour spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]de Campos Vieira Abib S, Chui CH, Cox S, et al. International Society of Paediatric Surgical Oncology (IPSO) surgical practice guidelines. Ecancermedicalscience. 2022 Feb 17;16:1356. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023308 http://www.ncbi.nlm.nih.gov/pubmed/35510137?tool=bestpractice.com
Palpation of renal vein and inferior vena cava identifies any tumour thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Suspicious metastatic lesions (hepatic or intra-abdominal) may be biopsied or resected at the time of initial surgery for diagnostic or therapeutic purposes. Decisions about extrapulmonary metastatic lesions are highly individualised.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com [106]Benedetti DJ, Varela CR, Renfro LA, et al. Treatment of children with favorable histology Wilms tumor with extrapulmonary metastases: a report from the COG studies AREN0533 and AREN03B2 and NWTSG study NWTS-5. Cancer. 2024 Mar 15;130(6):947-61. https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35099 http://www.ncbi.nlm.nih.gov/pubmed/37933882?tool=bestpractice.com
post-operative chemotherapy
Additional treatment recommended for SOME patients in selected patient group
Chemotherapy regimen depends on post-operative staging and histology of tumour.
International Society of Paediatric Oncology (SIOP) histological classification divides patients with all stages (I to IV) into 3 groups: low-risk (completely necrotic Wilms' tumour), high-risk (blastemal type and diffuse anaplasia), and intermediate-risk tumours (all other types).[53]Vujanić GM, Gessler M, Ooms AHAG, et al. The UMBRELLA SIOP-RTSG 2016 Wilms tumour pathology and molecular biology protocol. Nat Rev Urol. 2018 Nov;15(11):693-701. https://www.nature.com/articles/s41585-018-0100-3 http://www.ncbi.nlm.nih.gov/pubmed/30310143?tool=bestpractice.com [73]Vujanić GM, Parsons LN, D'Hooghe E, et al. Pathology of Wilms' tumour in International Society of Paediatric Oncology (SIOP) and Children's Oncology Group (COG) renal tumour studies: similarities and differences. Histopathology. 2022 Jun;80(7):1026-37. http://www.ncbi.nlm.nih.gov/pubmed/35275409?tool=bestpractice.com
SIOP low-risk patients: no post-operative chemotherapy.
SIOP intermediate-risk patients: post-operative chemotherapy with dactinomycin and vincristine (AV regimen) for 4 weeks.
SIOP high-risk patients: post-operative chemotherapy with dactinomycin, vincristine, and doxorubicin (AVD regimen) for 27 weeks.
See local specialist protocol for dosing guidelines.
Primary options
AV regimen
dactinomycin
and
vincristine
OR
AVD regimen
dactinomycin
and
vincristine
and
doxorubicin
preoperative chemotherapy
The UMBRELLA International Society of Paediatric Oncology (SIOP)-Renal Tumour Study Group (RTSG) 2016 protocol (known as the UMBRELLA protocol) recommends upfront chemotherapy for patients aged ≥6 months newly diagnosed with Wilms' tumour (prior to any attempt at resection regardless of initial stage).[73]Vujanić GM, Parsons LN, D'Hooghe E, et al. Pathology of Wilms' tumour in International Society of Paediatric Oncology (SIOP) and Children's Oncology Group (COG) renal tumour studies: similarities and differences. Histopathology. 2022 Jun;80(7):1026-37. http://www.ncbi.nlm.nih.gov/pubmed/35275409?tool=bestpractice.com [99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com
For children <6 months, the UMBRELLA protocol recommends upfront surgery and consideration of fine-needle biopsy for patients with unusual clinical presentations, or unusual findings on imaging, to decrease the risk of misdiagnosis of Wilms' tumour.[99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com [119]Jackson TJ, Brisse HJ, Pritchard-Jones K, et al. How we approach paediatric renal tumour core needle biopsy in the setting of preoperative chemotherapy: a review from the SIOP Renal Tumour Study Group. Pediatr Blood Cancer. 2022 Sep;69(9):e29702. https://onlinelibrary.wiley.com/doi/10.1002/pbc.29702 http://www.ncbi.nlm.nih.gov/pubmed/35587187?tool=bestpractice.com
SIOP any-risk: preoperative chemotherapy with dactinomycin and vincristine (AV regimen) for 4 weeks.
See local specialist protocol for dosing guidelines.
Primary options
AV regimen
dactinomycin
and
vincristine
surgery
Treatment recommended for ALL patients in selected patient group
After preoperative chemotherapy in patients aged ≥6 months, radical tumour nephrectomy is the standard of care.[99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com
The UMBRELLA protocol specifies that nephron-sparing surgery is acceptable for the following patients with non-syndromic unilateral Wilms' tumours: small tumour volume (<300 mL) and the expectation of a substantial remnant kidney function in patients with tumours <300 mL who never had lymph node involvement.[99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com
Surgeons should avoid tumour spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]de Campos Vieira Abib S, Chui CH, Cox S, et al. International Society of Paediatric Surgical Oncology (IPSO) surgical practice guidelines. Ecancermedicalscience. 2022 Feb 17;16:1356. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023308 http://www.ncbi.nlm.nih.gov/pubmed/35510137?tool=bestpractice.com
Palpation of renal vein and inferior vena cava identifies any tumour thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Suspicious metastatic lesions (hepatic or intra-abdominal) may be biopsied or resected at the time of initial surgery for diagnostic or therapeutic purposes. Decisions about extrapulmonary metastatic lesions are highly individualised.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com [106]Benedetti DJ, Varela CR, Renfro LA, et al. Treatment of children with favorable histology Wilms tumor with extrapulmonary metastases: a report from the COG studies AREN0533 and AREN03B2 and NWTSG study NWTS-5. Cancer. 2024 Mar 15;130(6):947-61. https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35099 http://www.ncbi.nlm.nih.gov/pubmed/37933882?tool=bestpractice.com
post-operative chemotherapy
Treatment recommended for ALL patients in selected patient group
Chemotherapy regimen depends on post-operative staging and histology of tumour.
International Society of Paediatric Oncology (SIOP) histological classification divides patients with all stages (I to IV) into 3 groups: low-risk (completely necrotic Wilms' tumour), high-risk (blastemal type and diffuse anaplasia), and intermediate-risk tumours (all other types).[53]Vujanić GM, Gessler M, Ooms AHAG, et al. The UMBRELLA SIOP-RTSG 2016 Wilms tumour pathology and molecular biology protocol. Nat Rev Urol. 2018 Nov;15(11):693-701. https://www.nature.com/articles/s41585-018-0100-3 http://www.ncbi.nlm.nih.gov/pubmed/30310143?tool=bestpractice.com [73]Vujanić GM, Parsons LN, D'Hooghe E, et al. Pathology of Wilms' tumour in International Society of Paediatric Oncology (SIOP) and Children's Oncology Group (COG) renal tumour studies: similarities and differences. Histopathology. 2022 Jun;80(7):1026-37. http://www.ncbi.nlm.nih.gov/pubmed/35275409?tool=bestpractice.com
SIOP low-risk patients: post-operative chemotherapy with dactinomycin and vincristine (AV regimen) for 27 weeks.
SIOP intermediate-risk patients (stromal or epithelial-type disease): post-operative chemotherapy with AV regimen for 27 weeks.
SIOP intermediate-risk patients (non-stromal- or non-epithelial-type disease, i.e., mixed and focal anaplasia-type tumours): post-operative chemotherapy with dactinomycin, vincristine, and doxorubicin (AVD regimen) for 27 weeks.
SIOP high-risk patients: post-operative chemotherapy with etoposide, carboplatin, cyclophosphamide, and doxorubicin (HR-1 regimen) for 34 weeks.
See local specialist protocol for dosing guidelines.
Primary options
AV regimen
dactinomycin
and
vincristine
OR
AVD regimen
dactinomycin
and
vincristine
and
doxorubicin
OR
HR-1 regimen
etoposide
and
carboplatin
and
cyclophosphamide
and
doxorubicin
radiotherapy
Additional treatment recommended for SOME patients in selected patient group
Flank irradiation is indicated in patients with high-risk diffuse anaplasia.[53]Vujanić GM, Gessler M, Ooms AHAG, et al. The UMBRELLA SIOP-RTSG 2016 Wilms tumour pathology and molecular biology protocol. Nat Rev Urol. 2018 Nov;15(11):693-701. https://www.nature.com/articles/s41585-018-0100-3 http://www.ncbi.nlm.nih.gov/pubmed/30310143?tool=bestpractice.com
preoperative chemotherapy
The UMBRELLA International Society of Paediatric Oncology (SIOP)-Renal Tumour Study Group (RTSG) 2016 protocol (known as the UMBRELLA protocol) recommends upfront chemotherapy for patients aged ≥6 months with newly diagnosed with Wilms' tumour (prior to any attempt at resection regardless of initial stage).[73]Vujanić GM, Parsons LN, D'Hooghe E, et al. Pathology of Wilms' tumour in International Society of Paediatric Oncology (SIOP) and Children's Oncology Group (COG) renal tumour studies: similarities and differences. Histopathology. 2022 Jun;80(7):1026-37. http://www.ncbi.nlm.nih.gov/pubmed/35275409?tool=bestpractice.com [99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com
For children <6 months, the UMBRELLA protocol recommends upfront surgery and consideration of fine-needle biopsy for patients with unusual clinical presentations, or unusual findings on imaging, to decrease the risk of misdiagnosis of Wilms' tumour.[99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com [119]Jackson TJ, Brisse HJ, Pritchard-Jones K, et al. How we approach paediatric renal tumour core needle biopsy in the setting of preoperative chemotherapy: a review from the SIOP Renal Tumour Study Group. Pediatr Blood Cancer. 2022 Sep;69(9):e29702. https://onlinelibrary.wiley.com/doi/10.1002/pbc.29702 http://www.ncbi.nlm.nih.gov/pubmed/35587187?tool=bestpractice.com
SIOP any risk: preoperative chemotherapy with dactinomycin and vincristine (AV regimen) for 4 weeks.
See local specialist protocol for dosing guidelines.
Primary options
AV regimen
dactinomycin
and
vincristine
surgery
Treatment recommended for ALL patients in selected patient group
After preoperative chemotherapy in patients aged ≥6 months, radical tumour nephrectomy is the standard of care.[99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com
The UMBRELLA protocol specifies that nephron-sparing surgery is acceptable for the following patients with non-syndromic unilateral Wilms' tumours: small tumour volume (<300 mL) and the expectation of a substantial remnant kidney function in patients with tumours <300 mL who never had lymph node involvement.[99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com
Surgeons should avoid tumour spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]de Campos Vieira Abib S, Chui CH, Cox S, et al. International Society of Paediatric Surgical Oncology (IPSO) surgical practice guidelines. Ecancermedicalscience. 2022 Feb 17;16:1356. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023308 http://www.ncbi.nlm.nih.gov/pubmed/35510137?tool=bestpractice.com
Palpation of renal vein and inferior vena cava identifies any tumour thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Suspicious metastatic lesions (hepatic or intra-abdominal) may be biopsied or resected at the time of initial surgery for diagnostic or therapeutic purposes. Decisions about extrapulmonary metastatic lesions are highly individualised.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com [106]Benedetti DJ, Varela CR, Renfro LA, et al. Treatment of children with favorable histology Wilms tumor with extrapulmonary metastases: a report from the COG studies AREN0533 and AREN03B2 and NWTSG study NWTS-5. Cancer. 2024 Mar 15;130(6):947-61. https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35099 http://www.ncbi.nlm.nih.gov/pubmed/37933882?tool=bestpractice.com
post-operative chemotherapy
Treatment recommended for ALL patients in selected patient group
Chemotherapy regimen depends on post-operative staging and histology of tumour.
International Society of Paediatric Oncology (SIOP) histological classification divides patients with all stages (I to IV) into 3 groups: low-risk (completely necrotic Wilms' tumour), high-risk (blastemal type and diffuse anaplasia), and intermediate-risk tumours (all other types).[53]Vujanić GM, Gessler M, Ooms AHAG, et al. The UMBRELLA SIOP-RTSG 2016 Wilms tumour pathology and molecular biology protocol. Nat Rev Urol. 2018 Nov;15(11):693-701. https://www.nature.com/articles/s41585-018-0100-3 http://www.ncbi.nlm.nih.gov/pubmed/30310143?tool=bestpractice.com [73]Vujanić GM, Parsons LN, D'Hooghe E, et al. Pathology of Wilms' tumour in International Society of Paediatric Oncology (SIOP) and Children's Oncology Group (COG) renal tumour studies: similarities and differences. Histopathology. 2022 Jun;80(7):1026-37. http://www.ncbi.nlm.nih.gov/pubmed/35275409?tool=bestpractice.com
SIOP low-risk patients: post-operative chemotherapy with dactinomycin and vincristine (AV regimen) for 27 weeks.
SIOP intermediate-risk patients (tumour volume after preoperative chemotherapy <500 mL of any subtype or tumour volume ≥500 mL of stromal or epithelial-type disease): post-operative chemotherapy with AV regimen for 27 weeks.
SIOP intermediate-risk patients (tumour volume ≥500 mL of non-stromal- or non-epithelial-type disease): post-operative chemotherapy with dactinomycin, vincristine, and doxorubicin (AVD regimen) for 27 weeks.
SIOP high-risk patients: post-operative chemotherapy with etoposide, carboplatin, cyclophosphamide, and doxorubicin (HR-1 regimen) for 34 weeks.
See local specialist protocol for dosing guidelines.
Primary options
AV regimen
dactinomycin
and
vincristine
OR
AVD regimen
dactinomycin
and
vincristine
and
doxorubicin
OR
HR-1 regimen
etoposide
and
carboplatin
and
cyclophosphamide
and
doxorubicin
radiotherapy
Additional treatment recommended for SOME patients in selected patient group
International Society of Paediatric Oncology (SIOP) low-risk patients: no irradiation.
SIOP intermediate-risk patients: flank irradiation is indicated.
SIOP high-risk patients: flank irradiation is indicated.
preoperative chemotherapy
The UMBRELLA International Society of Paediatric Oncology (SIOP)-Renal Tumour Study Group (RTSG) 2016 protocol (known as the UMBRELLA protocol) recommends upfront chemotherapy for patients aged ≥6 months with newly diagnosed with Wilms' tumour (prior to any attempt at resection regardless of initial stage).[73]Vujanić GM, Parsons LN, D'Hooghe E, et al. Pathology of Wilms' tumour in International Society of Paediatric Oncology (SIOP) and Children's Oncology Group (COG) renal tumour studies: similarities and differences. Histopathology. 2022 Jun;80(7):1026-37. http://www.ncbi.nlm.nih.gov/pubmed/35275409?tool=bestpractice.com [99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com
For children <6 months, the UMBRELLA protocol recommends upfront surgery and consideration of fine-needle biopsy for patients with unusual clinical presentations, or unusual findings on imaging, to decrease the risk of misdiagnosis of Wilms' tumour.[99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com [119]Jackson TJ, Brisse HJ, Pritchard-Jones K, et al. How we approach paediatric renal tumour core needle biopsy in the setting of preoperative chemotherapy: a review from the SIOP Renal Tumour Study Group. Pediatr Blood Cancer. 2022 Sep;69(9):e29702. https://onlinelibrary.wiley.com/doi/10.1002/pbc.29702 http://www.ncbi.nlm.nih.gov/pubmed/35587187?tool=bestpractice.com
SIOP any risk: preoperative chemotherapy with dactinomycin, vincristine, and doxorubicin (AVD regimen) for 6 weeks.
See local specialist protocol for dosing guidelines.
Primary options
AVD regimen
dactinomycin
and
vincristine
and
doxorubicin
surgery
Treatment recommended for ALL patients in selected patient group
After preoperative chemotherapy in patients aged ≥6 months, radical tumour nephrectomy is the standard of care.[99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com
Surgeons should avoid tumour spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]de Campos Vieira Abib S, Chui CH, Cox S, et al. International Society of Paediatric Surgical Oncology (IPSO) surgical practice guidelines. Ecancermedicalscience. 2022 Feb 17;16:1356. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023308 http://www.ncbi.nlm.nih.gov/pubmed/35510137?tool=bestpractice.com
Palpation of renal vein and inferior vena cava identifies any tumour thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com
Suspicious metastatic lesions (hepatic or intra-abdominal) may be either biopsied or resected at the time of initial surgery for diagnostic or therapeutic purposes. Decisions about extrapulmonary metastatic lesions are highly individualised.[52]Lopyan NM, Ehrlich PF. Surgical management of Wilms tumor (nephroblastoma) and renal cell carcinoma in children and young adults. Surg Oncol Clin N Am. 2021 Apr;30(2):305-23. http://www.ncbi.nlm.nih.gov/pubmed/33706902?tool=bestpractice.com [106]Benedetti DJ, Varela CR, Renfro LA, et al. Treatment of children with favorable histology Wilms tumor with extrapulmonary metastases: a report from the COG studies AREN0533 and AREN03B2 and NWTSG study NWTS-5. Cancer. 2024 Mar 15;130(6):947-61. https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35099 http://www.ncbi.nlm.nih.gov/pubmed/37933882?tool=bestpractice.com
post-operative chemotherapy
Treatment recommended for ALL patients in selected patient group
Post-operative chemotherapy decisions depend on restratification of patients based on response to treatment, histology of the primary tumour and the metastatic tumour (if resected), and the size of metastatic lesions.
International Society of Paediatric Oncology (SIOP) histological classification divides patients with all stages (I to IV) into 3 groups: low-risk (completely necrotic Wilms' tumour), high-risk (blastemal type and diffuse anaplasia), and intermediate-risk tumours (all other types).[53]Vujanić GM, Gessler M, Ooms AHAG, et al. The UMBRELLA SIOP-RTSG 2016 Wilms tumour pathology and molecular biology protocol. Nat Rev Urol. 2018 Nov;15(11):693-701. https://www.nature.com/articles/s41585-018-0100-3 http://www.ncbi.nlm.nih.gov/pubmed/30310143?tool=bestpractice.com [73]Vujanić GM, Parsons LN, D'Hooghe E, et al. Pathology of Wilms' tumour in International Society of Paediatric Oncology (SIOP) and Children's Oncology Group (COG) renal tumour studies: similarities and differences. Histopathology. 2022 Jun;80(7):1026-37. http://www.ncbi.nlm.nih.gov/pubmed/35275409?tool=bestpractice.com
SIOP low- or intermediate-risk patients (complete or very good partial remission of metastatic lesions to preoperative chemotherapy; representative metastatic nodule resection feasible and had completely necrotic metastasis): post-operative chemotherapy with dactinomycin, vincristine, and doxorubicin (AVD regimen) for 27 weeks.
SIOP low- or intermediate-risk patients (partial remission of metastatic lesions to preoperative chemotherapy and resection of metastatic nodules; representative nodule resection confirmed viable metastasis or metastatic nodule resection is not feasible): post-operative chemotherapy with etoposide, carboplatin, cyclophosphamide, and doxorubicin (HR-1 regimen) for 34 weeks.
SIOP high-risk: discuss best current treatment approach with the principal investigator for stage IV disease.
See local specialist protocol for dosing guidelines.
Primary options
AVD regimen
dactinomycin
and
vincristine
and
doxorubicin
OR
HR-1 regimen
etoposide
and
carboplatin
and
cyclophosphamide
and
doxorubicin
radiotherapy
Additional treatment recommended for SOME patients in selected patient group
Pulmonary radiotherapy is only administered for lung metastases lacking complete response by post-operative week 10 and in all cases with high-risk tumours, despite response to treatment.[4]Spreafico F, Fernandez CV, Brok J, et al. Wilms tumour. Nat Rev Dis Primers. 2021 Oct 14;7(1):75. https://www.nature.com/articles/s41572-021-00308-8 http://www.ncbi.nlm.nih.gov/pubmed/34650095?tool=bestpractice.com [99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com
Consider irradiation to metastases in low-risk disease if resection of nodule resection is not feasible.
Irradiation to metastases in intermediate- and high-risk disease is indicated.
preoperative chemotherapy
In bilateral Wilms' tumour, preoperative chemotherapy with dactinomycin and vincristine (AV regimen) for a maximum of 12 weeks with evaluation of response at 6 weeks followed by surgery.
See local specialist protocol for dosing guidelines.
Primary options
AV regimen
dactinomycin
and
vincristine
surgery
Treatment recommended for ALL patients in selected patient group
Nephron-sparing surgery is advocated for bilateral disease; this may include tumourectomy, wedge resection, polar resection, heminephrectomy, nephrectomy on one side, and partial resection, thus avoiding bilateral radical nephrectomies.[120]Kieran K, Davidoff AM. Nephron-sparing surgery for bilateral Wilms tumor. Pediatr Surg Int. 2015 Mar;31(3):229-36. http://www.ncbi.nlm.nih.gov/pubmed/25633157?tool=bestpractice.com
The UMBRELLA protocol recommends discussion with the International Society of Paediatric Oncology-Renal Tumour Study Group (SIOP-RTSG) surgical panel to assess the feasibility of nephron-sparing surgery and minimise the risk of upstaging by incomplete resection of the tumour.[99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com
post-operative chemotherapy
Treatment recommended for ALL patients in selected patient group
Each tumour is subclassified and staged separately to determine post-operative chemotherapy.
See local specialist protocol for regimen and dosing guidelines.
tumour recurrence
individualised treatment
Treatment of recurrent Wilms' tumours must be individualised to the patient, based on prior chemotherapy treatment, as well as the location of relapse.
Recurrent tumours are typically managed with chemotherapy agents that were not used for primary therapy.[99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com [121]Speafico F, Pritchard Jones K, Malogolowkin MH, et al. Treatment of relapsed Wilms tumors: lessons learned. Expert Rev Anticancer Ther. 2009 Dec;9(12):1807-15. http://www.ncbi.nlm.nih.gov/pubmed/19954292?tool=bestpractice.com [122]Oostveen RM, Pritchard-Jones K. Pharmacotherapeutic management of Wilms tumor: an update. Paediatr Drugs. 2019 Feb;21(1):1-13. http://www.ncbi.nlm.nih.gov/pubmed/30604241?tool=bestpractice.com [123]Malogolowkin M, Cotton CA, Green DM, et al. Treatment of Wilms tumor relapsing after initial treatment with vincristine, actinomycin D, and doxorubicin. A report from the National Wilms Tumor Study Group. Pediatr Blood Cancer. 2008 Feb;50(2):236-41. http://www.ncbi.nlm.nih.gov/pubmed/17539021?tool=bestpractice.com [124]Green DM, Cotton CA, Malogolowkin M, et al. Treatment of Wilms tumor relapsing after initial treatment with vincristine and actinomycin D: a report from the National Wilms Tumor Study Group. Pediatr Blood Cancer. 2007 May;48(5):493-9. http://www.ncbi.nlm.nih.gov/pubmed/16547940?tool=bestpractice.com [125]Schneller N, Daw N, Throckmorton W, et al. Outcomes of relapsed favorable-histology Wilms tumor in non-clinical trial setting. Pediatr Blood Cancer. 2025 Jan;72(1):e31347. http://www.ncbi.nlm.nih.gov/pubmed/39394977?tool=bestpractice.com
The use of high-dose chemotherapy with autologous stem cell rescue or clinical trials utilising novel chemotherapy regimens or agents may be considered.[99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com [126]Dome JS, Graf N, Geller JI, et al. Advances in Wilms tumor treatment and biology: progress through international collaboration. J Clin Oncol. 2015 Sep 20;33(27):2999-3007. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567702 http://www.ncbi.nlm.nih.gov/pubmed/26304882?tool=bestpractice.com [127]Malogolowkin MH, Hemmer MT, Le-Rademacher J, et al. Outcomes following autologous hematopoietic stem cell transplant for patients with relapsed Wilms' tumor: a CIBMTR retrospective analysis. Bone Marrow Transplant. 2017 Nov;52(11):1549-55. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5665725 http://www.ncbi.nlm.nih.gov/pubmed/28869618?tool=bestpractice.com [128]Brok J, Mavinkurve-Groothuis AMC, Drost J, et al. Unmet needs for relapsed or refractory Wilms tumour: mapping the molecular features, exploring organoids and designing early phase trials - a collaborative SIOP-RTSG, COG and ITCC session at the first SIOPE meeting. Eur J Cancer. 2021 Feb;144:113-22. http://www.ncbi.nlm.nih.gov/pubmed/33341445?tool=bestpractice.com
Local control using surgery and/or radiation is highly individualised to the patient. Surgical resection of relapsed disease is considered when complete resection seems possible or when it is useful to evaluate histological tumour response.[99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com
The use of radiotherapy to initially non-irradiated sites is accepted, but the approach to previously irradiated sites must be individualised.[99]van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol. 2017 Dec;14(12):743-52. https://www.nature.com/articles/nrurol.2017.163 http://www.ncbi.nlm.nih.gov/pubmed/29089605?tool=bestpractice.com
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