Wilms tumor

Plus – observation or postoperative chemotherapy

Back

1st line –

surgery

Upfront nephrectomy using a transperitoneal approach is recommended for patients with unilateral renal masses who do not have a known Wilms tumor predisposition.[4][52]

Surgeons should avoid tumor spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[48][94]

Palpation of renal vein and inferior vena cava identifies any tumor thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]

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 individualized.[52][106]

Back

Plus –

observation or postoperative chemotherapy

Treatment recommended for ALL patients in selected patient group

Favorable histology Wilms tumors are subdivided by the Children's Oncology Group (COG) into recurrence risk categories (based on patient age, tumor weight, stage, molecular markers, and biologic factors), which determine postoperative treatment.[95][96]

COG very-low-risk patients (stage I, <2 years of age, <550 g tumor 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 radiation therapy).[98][109]

COG low-risk patients (stage I, any age or tumor weight, without LOH at combined 1p and 16q): postoperative chemotherapy with vincristine and dactinomycin (EE-4A regimen).[109]

COG standard-risk patients (stage I, with LOH at combined 1p and 16q): postoperative chemotherapy with vincristine, dactinomycin, and doxorubicin (DD-4A regimen).[109][110]

See local specialist protocol for dosing guidelines.

Primary options

EE-4A regimen

vincristine

and

dactinomycin

DD-4A regimen

vincristine

and

dactinomycin

and

doxorubicin

favorable histology: stage II

Back

1st line –

surgery

Upfront nephrectomy using a transperitoneal approach is recommended for patients with unilateral renal masses who do not have a known Wilms tumor predisposition.[4][52]

Surgeons should avoid tumor spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]

Palpation of renal vein and inferior vena cava identifies any tumor thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]

favorable histology: resectable, stage III

Back

Plus –

postoperative chemotherapy

Treatment recommended for ALL patients in selected patient group

Chemotherapy regimen for stage II disease depends on the biology of the tumor.

COG low-risk patients (stage II, without loss of heterozygosity [LOH] at combined 1p and 16q): postoperative chemotherapy with vincristine and dactinomycin (EE-4A regimen).[109]

COG standard-risk patients (stage II, with LOH at combined 1p and 16q): postoperative chemotherapy with vincristine, dactinomycin, and doxorubicin (DD-4A regimen).[109][110]

See local specialist protocol for dosing guidelines.

Primary options

EE-4A regimen

vincristine

and

dactinomycin

DD-4A regimen

vincristine

and

dactinomycin

and

doxorubicin

Back

1st line –

surgery

Upfront nephrectomy using a transperitoneal approach is recommended for patients with unilateral renal masses who do not have a known Wilms tumor predisposition.[4][52]

Surgeons should avoid tumor spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]

Palpation of renal vein and inferior vena cava identifies any tumor thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]

Back

Plus –

postoperative chemotherapy

Treatment recommended for ALL patients in selected patient group

Chemotherapy regimen for stage III disease depends on the biology of the tumor.

COG standard-risk patients (stage III, with no loss of heterozygosity [LOH] at combined 1p and 16q): postoperative chemotherapy with vincristine, dactinomycin, and doxorubicin (DD-4A regimen).[109][110]

COG higher-risk patients (stage III, with LOH at combined 1p and 16q): postoperative chemotherapy with DD-4A regimen for 6 weeks, and then switched to vincristine, dactinomycin, doxorubicin, cyclophosphamide, and etoposide (regimen M).[109][110]

See local specialist protocol for dosing guidelines.

Primary options

DD-4A regimen

vincristine

and

dactinomycin

and

doxorubicin

Regimen M

vincristine

and

dactinomycin

and

doxorubicin

and

cyclophosphamide

and

etoposide

favorable histology: resectable, stage IV

Back

Plus –

radiation therapy

Treatment recommended for ALL patients in selected patient group

All stage III tumors receive either flank irradiation or whole abdomen irradiation.[109][110]

Radiation therapy (either flank irradiation or whole abdomen irradiation) is used for the regional management of local stage III favorable histology Wilms tumor.[4] In most cases, flank radiation is used; whole abdominal radiation is only used in cases with peritoneal seeding, preoperative tumor rupture, or an intraoperative spill that is widespread in the opinion of the operating surgeon.[52][99][129]

Back

1st line –

surgery

Upfront nephrectomy using a transperitoneal approach is recommended for patients with unilateral renal masses who do not have a known Wilms tumor predisposition.[4][52]

Surgeons should avoid tumor spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]

Palpation of renal vein and inferior vena cava identifies any tumor thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]

Back

Plus –

postoperative chemotherapy

Treatment recommended for ALL patients in selected patient group

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): postoperative chemotherapy with vincristine, dactinomycin, and doxorubicin (DD-4A regimen).[109] Patients with pulmonary metastases with a complete response at week 6 continue receiving DD-4A without whole lung irradiation.[71] 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] 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]

COG higher-risk patients (stage IV, with LOH at combined 1p and 16q, or metastases to site other than lungs): postoperative chemotherapy with DD-4A regimen for 6 weeks, and then switched to regimen M.[109][110]

See local specialist protocol for dosing guidelines.

Primary options

DD-4A regimen

vincristine

and

dactinomycin

and

doxorubicin

Regimen M

vincristine

and

dactinomycin

and

doxorubicin

and

cyclophosphamide

and

etoposide

favorable histology: unresectable, stage III-IV

Back

Consider –

radiation therapy

Treatment recommended for SOME patients in selected patient group

Radiation therapy (either flank irradiation or whole abdomen irradiation) is used for the regional management of local stage III favorable histology Wilms tumor (staging at primary tumor regardless of metastases).[4] In most cases, flank radiation is used; whole abdominal radiation is only used in cases with peritoneal seeding, preoperative tumor rupture, or an intraoperative spill that is widespread in the opinion of the operating surgeon.[52][99][129]

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][109]

Standard-risk patients with pulmonary metastases with a complete response at week 6 continue chemotherapy without whole lung irradiation.[71] 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]

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 nonlung metastatic sites.[109][110]

Treatment of extrapulmonary metastatic lesions is highly individualized.[106]

Back

1st line –

preoperative chemotherapy

Patients who cannot undergo upfront nephrectomy have a tumor biopsy performed, followed by neoadjuvant chemotherapy until delayed nephrectomy. Chemotherapy is then completed postoperatively.

The Children's Oncology Group (COG) recommends upfront biopsy and preoperative chemotherapy if the tumor extends into inferior vena cava above the hepatic vein or the primary tumor is unresectable at presentation.[52]

If a tumor is unresectable, COG recommends an open biopsy or core needle biopsy with a minimum of 10-12 nonnecrotic cores to ensure sufficient tissue for molecular testing. Performing a tumor biopsy results in upstaging to local stage III disease.[4][52]

Preoperative chemotherapy is used to reduce the size of the tumor. 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

Regimen M

vincristine

and

dactinomycin

and

doxorubicin

and

cyclophosphamide

and

etoposide

Back

Plus –

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, favorable histology tumors.[4][52]

Surgeons should avoid tumor spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]

Palpation of renal vein and inferior vena cava identifies any tumor thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]

Back

Plus –

postoperative chemotherapy

Treatment recommended for ALL patients in selected patient group

Postoperative 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

Regimen M

vincristine

and

dactinomycin

and

doxorubicin

and

cyclophosphamide

and

etoposide

favorable histology: stage V

Back

Plus –

radiation therapy

Treatment recommended for ALL patients in selected patient group

Stage IV standard-risk patients with pulmonary metastases who do not show complete response to chemotherapy at week 6 receive whole lung irradiation.[71]

Stage IV higher-risk patients receive whole lung irradiation or radiation therapy to nonlung sites of metastasis.[109][110] Treatment of extrapulmonary metastatic lesions is highly individualized.[106]

Back

1st line –

preoperative chemotherapy

In patients with bilateral Wilms tumor or bilaterally predisposed unilateral Wilms tumor, preoperative chemotherapy is followed by nephron-sparing surgery and modified postoperative chemotherapy based on histologic response.[97][109][113]

The goal of preoperative chemotherapy is to shrink the tumor to allow maximum preservation of renal parenchyma.[97]

For patients with bilateral Wilms tumor, or with bilaterally predisposed unilateral Wilms tumor with metastatic disease: vincristine, dactinomycin, and doxorubicin (VAD regimen) are given preoperatively.[113]

For patients with bilaterally predisposed unilateral Wilms tumor that is localized (no metastatic disease): vincristine and dactinomycin (VA regimen) are used preoperatively.[113]

See local specialist protocol for dosing guidelines.

Primary options

VAD regimen

vincristine

and

dactinomycin

and

doxorubicin

VA regimen

vincristine

and

dactinomycin

Back

Plus –

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]

Consider – renal transplant

Back

Plus –

postoperative chemotherapy

Treatment recommended for ALL patients in selected patient group

Postoperative chemotherapy is based on stage and histologic response.[97][109][113]

Each kidney should be individually staged and treated accordingly.

See local specialist protocol for regimen and dosing guidelines.

Back

Consider –

renal transplant

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]

anaplastic histology: stage I

Back

1st line –

surgery

Upfront nephrectomy using a transperitoneal approach is recommended for patients with unilateral renal masses who do not have a known Wilms tumor predisposition.[4][52]

Surgeons should avoid tumor spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]

Palpation of renal vein and inferior vena cava identifies any tumor thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]

Back

Plus –

postoperative chemotherapy

Treatment recommended for ALL patients in selected patient group

Stage I patients with either focal or diffuse anaplasia receive postoperative chemotherapy with vincristine, dactinomycin, and doxorubicin (DD-4A regimen).[115][116]

See local specialist protocol for dosing guidelines.

Primary options

DD-4A regimen

vincristine

and

dactinomycin

and

doxorubicin

anaplastic histology: stage II

Back

Plus –

radiation therapy

Treatment recommended for ALL patients in selected patient group

Stage I patients with either focal or diffuse anaplasia receive flank irradiation.[115][116]

Back

1st line –

surgery

Upfront nephrectomy using a transperitoneal approach is recommended for patients with unilateral renal masses who do not have a known Wilms tumor predisposition.[4][52]

Surgeons should avoid tumor spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]

Palpation of renal vein and inferior vena cava identifies any tumor thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]

Back

Plus –

postoperative chemotherapy

Treatment recommended for ALL patients in selected patient group

Treatment regimen depends on whether anaplasia is focal or diffuse.

Focal anaplasia: postoperative chemotherapy with vincristine, dactinomycin, and doxorubicin (DD-4A regimen).[116][117]

Diffuse anaplasia: postoperative chemotherapy with vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan (revised UH-2 regimen).[109][118]

See local specialist protocol for dosing guidelines.

Primary options

DD-4A regimen

vincristine

and

dactinomycin

and

doxorubicin

revised UH-2 regimen

vincristine

and

doxorubicin

and

cyclophosphamide

and

carboplatin

and

etoposide

and

irinotecan

anaplastic histology: stage III

Back

Plus –

radiation therapy

Treatment recommended for ALL patients in selected patient group

Patients with focal or diffuse anaplasia should receive flank irradiation.[109][116][117]

Back

1st line –

surgery

Upfront nephrectomy using a transperitoneal approach is recommended for patients with unilateral renal masses who do not have a known Wilms tumor predisposition.[4][52]

Surgeons should avoid tumor spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]

Palpation of renal vein and inferior vena cava identifies any tumor thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]

Back

Plus –

postoperative chemotherapy

Treatment recommended for ALL patients in selected patient group

Treatment regimen depends on whether anaplasia is focal or diffuse.

Focal anaplasia: postoperative chemotherapy with vincristine, dactinomycin, and doxorubicin (DD-4A regimen).[116][117]

Diffuse anaplasia: postoperative chemotherapy with vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan (revised UH-2 regimen).[109][118]

See local specialist protocol for dosing guidelines.

Primary options

DD-4A regimen

vincristine

and

dactinomycin

and

doxorubicin

revised UH-2 regimen

vincristine

and

doxorubicin

and

cyclophosphamide

and

carboplatin

and

etoposide

and

irinotecan

anaplastic histology: stage IV

Back

Plus –

radiation therapy

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 tumor.[109][116][117]

Back

1st line –

surgery

Upfront nephrectomy using a transperitoneal approach is recommended for patients with unilateral renal masses who do not have a known Wilms tumor predisposition.[4][52]

Surgeons should avoid tumor spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]

Palpation of renal vein and inferior vena cava identifies any tumor thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]

Back

Plus –

postoperative chemotherapy

Treatment recommended for ALL patients in selected patient group

Treatment regimen depends on whether anaplasia is focal or diffuse.

Focal anaplasia: postoperative chemotherapy with vincristine, doxorubicin, cyclophosphamide, carboplatin, and etoposide (revised UH-1 regimen).[116][117]

Diffuse anaplasia: vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan (revised UH-2 regimen).[109][118]

See local specialist protocol for dosing guidelines.

Primary options

revised UH-1 regimen

vincristine

and

doxorubicin

and

cyclophosphamide

and

carboplatin

and

etoposide

revised UH-2 regimen

vincristine

and

doxorubicin

and

cyclophosphamide

and

carboplatin

and

etoposide

and

irinotecan

anaplastic histology: stage V

Back

Plus –

radiation therapy

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 tumor.[109][117] Radiation therapy is given to metastatic sites.

Back

1st line –

preoperative chemotherapy

The goal of preoperative chemotherapy is to shrink the tumor to allow maximum preservation of renal parenchyma.[97]

For patients with bilaterally predisposed unilateral Wilms tumor that is localized (no metastatic disease): vincristine and dactinomycin (VA regimen) is used preoperatively.[113]

See local specialist protocol for dosing guidelines.

Primary options

VAD regimen

vincristine

and

dactinomycin

and

doxorubicin

VA regimen

vincristine

and

dactinomycin

Back

Plus –

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]

Consider – renal transplant

Back

Plus –

postoperative chemotherapy

Treatment recommended for ALL patients in selected patient group

Postoperative chemotherapy is based on stage and histologic response.[97][109][113]

Each kidney should be staged individually and treated accordingly.

See local specialist protocol for dosing guidelines.

Back

Consider –

renal transplant

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]

SIOP criteria

stage I

Back

1st line –

preoperative chemotherapy

The UMBRELLA International Society of Paediatric Oncology (SIOP)-Renal Tumor Study Group (RTSG) 2016 protocol (known as the UMBRELLA protocol) recommends upfront chemotherapy for patients age ≥6 months newly diagnosed with Wilms tumor (prior to any attempt at resection regardless of initial stage).[73][99]

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 tumor.[99][119]

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

Consider – postoperative chemotherapy

Back

Plus –

surgery

Treatment recommended for ALL patients in selected patient group

After preoperative chemotherapy in patients age ≥6 months, radical tumor nephrectomy is the standard of care.[99]

The UMBRELLA protocol specifies that nephron-sparing surgery is acceptable for the following patients with nonsyndromic unilateral Wilms tumors: small tumor volume (<300 mL) and the expectation of a substantial remnant kidney function in patients with tumors <300 mL who never had lymph node involvement.[99]

Surgeons should avoid tumor spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]

Palpation of renal vein and inferior vena cava identifies any tumor thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]

Back

Consider –

postoperative chemotherapy

Treatment recommended for SOME patients in selected patient group

Chemotherapy regimen depends on postoperative staging and histology of tumor.

International Society of Paediatric Oncology (SIOP) histologic classification divides patients with all stages (I through IV) into 3 groups: low-risk (completely necrotic Wilms tumor), high-risk (blastemal type and diffuse anaplasia), and intermediate-risk tumors (all other types).[53][73]

SIOP low-risk patients: no postoperative chemotherapy.

SIOP intermediate-risk patients: postoperative chemotherapy with dactinomycin and vincristine (AV regimen) for 4 weeks.

SIOP high-risk patients: postoperative 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

AVD regimen

dactinomycin

and

vincristine

and

doxorubicin

stage II

Back

1st line –

preoperative chemotherapy

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

Back

Plus –

surgery

Treatment recommended for ALL patients in selected patient group

After preoperative chemotherapy in patients age ≥6 months, radical tumor nephrectomy is the standard of care.[99]

Surgeons should avoid tumor spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]

Palpation of renal vein and inferior vena cava identifies any tumor thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]

Back

Plus –

postoperative chemotherapy

Treatment recommended for ALL patients in selected patient group

Chemotherapy regimen depends on postoperative staging and histology of tumor.

SIOP low-risk patients: postoperative chemotherapy with dactinomycin and vincristine (AV regimen) for 27 weeks.

SIOP intermediate-risk patients (stromal or epithelial-type disease): postoperative chemotherapy with AV regimen for 27 weeks.

SIOP intermediate-risk patients (nonstromal- or nonepithelial-type disease, i.e., mixed and focal anaplasia-type tumors): postoperative chemotherapy with dactinomycin, vincristine, and doxorubicin (AVD regimen) for 27 weeks.

SIOP high-risk patients: postoperative 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

AVD regimen

dactinomycin

and

vincristine

and

doxorubicin

HR-1 regimen

etoposide

and

carboplatin

and

cyclophosphamide

and

doxorubicin

Back

Consider –

radiation therapy

Treatment recommended for SOME patients in selected patient group

Flank irradiation is indicated in patients with high-risk diffuse anaplasia.[53]

stage III

Back

1st line –

preoperative chemotherapy

The UMBRELLA International Society of Paediatric Oncology (SIOP)-Renal Tumor Study Group (RTSG) 2016 protocol (known as the UMBRELLA protocol) recommends upfront chemotherapy for patients age ≥6 months with newly diagnosed with Wilms tumor (prior to any attempt at resection regardless of initial stage).[73][99]

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

Back

Plus –

surgery

Treatment recommended for ALL patients in selected patient group

After preoperative chemotherapy in patients age ≥6 months, radical tumor nephrectomy is the standard of care.[99]

Surgeons should avoid tumor spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]

Palpation of renal vein and inferior vena cava identifies any tumor thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]

Back

Plus –

postoperative chemotherapy

Treatment recommended for ALL patients in selected patient group

Chemotherapy regimen depends on postoperative staging and histology of tumor.

SIOP low-risk patients: postoperative chemotherapy with dactinomycin and vincristine (AV regimen) for 27 weeks.

SIOP intermediate-risk patients (tumor volume after preoperative chemotherapy <500 mL of any subtype or tumor volume ≥500 mL of stromal or epithelial-type disease): postoperative chemotherapy with AV regimen for 27 weeks.

SIOP intermediate-risk patients (tumor volume ≥500 mL of nonstromal- or nonepithelial-type disease): postoperative chemotherapy with dactinomycin, vincristine, and doxorubicin (AVD regimen) for 27 weeks.

SIOP high-risk patients: postoperative 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

AVD regimen

dactinomycin

and

vincristine

and

doxorubicin

HR-1 regimen

etoposide

and

carboplatin

and

cyclophosphamide

and

doxorubicin

Back

Consider –

radiation therapy

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.

stage IV

Back

1st line –

preoperative chemotherapy

The UMBRELLA International Society of Paediatric Oncology (SIOP)-Renal Tumor Study Group (RTSG) 2016 protocol (known as the UMBRELLA protocol) recommends upfront chemotherapy for patients age ≥6 months with newly diagnosed with Wilms tumor (prior to any attempt at resection regardless of initial stage).[73][99]

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

Back

Plus –

surgery

Treatment recommended for ALL patients in selected patient group

After preoperative chemotherapy in patients age ≥6 months, radical tumor nephrectomy is the standard of care.[99]

Surgeons should avoid tumor spillage or incomplete removal. Selective sampling of lymph nodes should be performed.[94]

Palpation of renal vein and inferior vena cava identifies any tumor thrombi (usually free-floating) and may allow for careful removal of thrombus.[52]

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 individualized.[52][106]

Back

Plus –

postoperative chemotherapy

Treatment recommended for ALL patients in selected patient group

Postoperative chemotherapy decisions depend on restratification of patients based on response to treatment, histology of the primary tumor and the metastatic tumor (if resected), and the size of metastatic lesions.

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): postoperative 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): postoperative 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

HR-1 regimen

etoposide

and

carboplatin

and

cyclophosphamide

and

doxorubicin

Back

Consider –

radiation therapy

Treatment recommended for SOME patients in selected patient group

Pulmonary radiation therapy is only administered for lung metastases lacking complete response by postoperative week 10 and in all cases with high-risk tumors, despite response to treatment.[4][99]

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.

stage V

Back

1st line –

preoperative chemotherapy

In bilateral Wilms tumor, 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

Back

Plus –

surgery

Treatment recommended for ALL patients in selected patient group

Nephron-sparing surgery is advocated for bilateral disease; this may include tumorectomy, wedge resection, polar resection, heminephrectomy, nephrectomy on one side and partial resection, thus avoiding bilateral radical nephrectomies.[120]

The UMBRELLA protocol recommends discussion with the International Society of Paediatric Oncology-Renal Tumor Study Group (SIOP-RTSG) surgical panel to assess the feasibility of nephron-sparing surgery and minimize the risk of upstaging by incomplete resection of the tumor.[99]