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Treatment of pulmonary nodules and metastases
Source: Wilms Tumor and Other Childhood Kidney Tumors Treatment (PDQ®)–Health Professional Version, National Cancer Institute.
Source updated: April 15, 2025 · Captured 2026-09-09.
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Context: Wilms Tumor / Treatment of Wilms Tumor / Treatment of stage IV Wilms tumor
Historically, chest x-rays were used to detect pulmonary metastases. The introduction of CT created controversy because many patients had lung nodules detected by chest CT scans that were not seen on chest x-rays. Management of newly diagnosed patients with FH Wilms tumor who have lung nodules detected only by CT scans (with negative chest x-ray) has elicited controversy as to whether they need to be treated with additional intensive treatment that is accompanied by acute and late toxicities.
Evidence (treatment of pulmonary nodules detected by chest CT scan only):
A retrospective review of 186 patients from NWTS-4 and NWTS-5 with CT-only–detected lung nodules reported on the use of doxorubicin, vincristine, and dactinomycin versus the use of two drugs.[280]
A retrospective review of 186 patients from NWTS-4 and NWTS-5 with CT-only–detected lung nodules reported on the use of doxorubicin, vincristine, and dactinomycin versus the use of two drugs.[280]
Patients who received doxorubicin, vincristine, and dactinomycin with or without lung irradiation had a 5-year EFS rate of 80% versus an EFS rate of 56% for patients receiving only two drugs (P = .004).
A retrospective review of 186 patients from NWTS-4 and NWTS-5 with CT-only–detected lung nodules reported on the use of doxorubicin, vincristine, and dactinomycin versus the use of two drugs.[280]
There was no difference in EFS according to whether the lung was irradiated.
A retrospective review of 186 patients from NWTS-4 and NWTS-5 with CT-only–detected lung nodules reported on the use of doxorubicin, vincristine, and dactinomycin versus the use of two drugs.[280]
There was no difference in the 5-year OS rate (87% vs. 86%).
Retrospective studies from Europe have examined the impact of omitting pulmonary radiation in patients with pulmonary metastases diagnosed by chest x-ray. European investigators omitted radiation from the treatment of most patients with Wilms tumor and pulmonary metastases as identified on chest x-ray who were treated on the SIOP-93-01 (NCT00003804) trial. The European approach to renal tumors differs from the approach used in North America. All patients who were shown to have a renal tumor by imaging underwent 9 weeks of prenephrectomy chemotherapy consisting of vincristine, dactinomycin, and doxorubicin.
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Evidence (omission of pulmonary irradiation):
In a retrospective SIOP study, 234 newly diagnosed patients with Wilms tumor presenting with pulmonary metastases were treated according to the response of the pulmonary metastases to the prenephrectomy chemotherapy.[281]
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In a retrospective SIOP study, 234 newly diagnosed patients with Wilms tumor presenting with pulmonary metastases were treated according to the response of the pulmonary metastases to the prenephrectomy chemotherapy.[281]
Patients who were in complete remission (67%) after 6 weeks of therapy continued with the same chemotherapy and did not require radiation to their lungs.
In a retrospective SIOP study, 234 newly diagnosed patients with Wilms tumor presenting with pulmonary metastases were treated according to the response of the pulmonary metastases to the prenephrectomy chemotherapy.[281] › Patients who were in complete remission (67%) after 6 weeks of therapy continued with the same chemotherapy and did not require radiation to their lungs.
The 5-year EFS rate was 77%, and the OS rate was 88%.
In a retrospective SIOP study, 234 newly diagnosed patients with Wilms tumor presenting with pulmonary metastases were treated according to the response of the pulmonary metastases to the prenephrectomy chemotherapy.[281]
Patients who had residual pulmonary metastases were evaluated for metastasectomy.
In a retrospective SIOP study, 234 newly diagnosed patients with Wilms tumor presenting with pulmonary metastases were treated according to the response of the pulmonary metastases to the prenephrectomy chemotherapy.[281] › Patients who had residual pulmonary metastases were evaluated for metastasectomy.
Thirty-seven patients (17%) obtained complete remission with surgery, and their outcome was similar to that of the group of patients who were treated with chemotherapy. Tumor viability in the resected pulmonary metastases was not a factor for omitting radiation therapy.
In a retrospective SIOP study, 234 newly diagnosed patients with Wilms tumor presenting with pulmonary metastases were treated according to the response of the pulmonary metastases to the prenephrectomy chemotherapy.[281] › Patients who had residual pulmonary metastases were evaluated for metastasectomy.
The 5-year EFS rate was 84%, and the OS rate was 92%.
In a retrospective SIOP study, 234 newly diagnosed patients with Wilms tumor presenting with pulmonary metastases were treated according to the response of the pulmonary metastases to the prenephrectomy chemotherapy.[281]
Patients with residual pulmonary metastases that were incompletely resected or inoperable received more aggressive chemotherapy consisting of ifosfamide/anthracycline alternating with carboplatin/etoposide for 9 weeks.
In a retrospective SIOP study, 234 newly diagnosed patients with Wilms tumor presenting with pulmonary metastases were treated according to the response of the pulmonary metastases to the prenephrectomy chemotherapy.[281] › Patients with residual pulmonary metastases that were incompletely resected or inoperable received more aggressive chemotherapy consisting of ifosfamide/anthracycline alternating with carboplatin/etoposide for 9 weeks.
Patients showing a complete remission at that time were spared pulmonary radiation and continued with chemotherapy, whereas patients with residual pulmonary metastases continued with additional chemotherapy (to complete 34 weeks) and pulmonary irradiation. The 5-year OS rate was 48%, compared with the OS rates for patients who responded to chemotherapy alone (88%) and those who underwent metastasectomy (92%) (P < .001).
In a retrospective SIOP study, 234 newly diagnosed patients with Wilms tumor presenting with pulmonary metastases were treated according to the response of the pulmonary metastases to the prenephrectomy chemotherapy.[281] › Patients with residual pulmonary metastases that were incompletely resected or inoperable received more aggressive chemotherapy consisting of ifosfamide/anthracycline alternating with carboplatin/etoposide for 9 weeks.
Patients with high-risk histologies, such as anaplastic Wilms tumor, were treated with more aggressive chemotherapy but had a poorer outcome, compared with that of patients with nonanaplastic histologies (5-year OS rate, 33% vs. 87%; P < .001).
Based on the European experience, the COG AREN0533 (NCT00379340) study applied a new strategy for patients with FH Wilms tumor and isolated lung metastases to improve EFS while reducing exposure to lung irradiation. Therapy was adjusted based on lung nodule response and tumor-specific loss of heterozygosity at 1p and 16q.[266][Level of evidence C2]
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Based on the European experience, the COG AREN0533 (NCT00379340) study applied a new strategy for patients with FH Wilms tumor and isolated lung metastases to improve EFS while reducing exposure to lung irradiation. Therapy was adjusted based on lung nodule response and tumor-specific loss of heterozygosity at 1p and 16q.[266][Level of evidence C2]
Of the 292 patients enrolled in the study, 133 patients (42%) showed a complete lung nodule response after 6 weeks of DD-4A (vincristine, dactinomycin, doxorubicin) and continued receiving the same chemotherapy without lung radiation therapy. The 4-year EFS rate was 80%, and OS rate was 96%.
Based on the European experience, the COG AREN0533 (NCT00379340) study applied a new strategy for patients with FH Wilms tumor and isolated lung metastases to improve EFS while reducing exposure to lung irradiation. Therapy was adjusted based on lung nodule response and tumor-specific loss of heterozygosity at 1p and 16q.[266][Level of evidence C2]
Patients who had an incomplete lung nodule response (n = 145) or loss of heterozygosity at 1p/16q (n = 18) received lung radiation therapy and four cycles of cyclophosphamide/etoposide in addition to the DD-4A drugs (regimen M). The 4-year EFS rate was 89%, and the OS rate was 95% for the incomplete lung nodule response group without loss of heterozygosity. Of the patients with pulmonary metastases only and loss of heterozygosity, the 4-year EFS and OS rates were 100%.
Based on the European experience, the COG AREN0533 (NCT00379340) study applied a new strategy for patients with FH Wilms tumor and isolated lung metastases to improve EFS while reducing exposure to lung irradiation. Therapy was adjusted based on lung nodule response and tumor-specific loss of heterozygosity at 1p and 16q.[266][Level of evidence C2]
In a post hoc analysis of 1q gain in 212 patients enrolled in AREN0533 who had DNA available, patients with lung nodule complete remission with 1q gain had a significantly worse 4-year EFS rate (57% vs. 86%, P = .001) and trend toward inferior OS rates (89% vs. 97%). Relapses were predominantly pulmonary. There was no difference in outcome for patients with incomplete lung nodule response based on 1q gain.
Based on the European experience, the COG AREN0533 (NCT00379340) study applied a new strategy for patients with FH Wilms tumor and isolated lung metastases to improve EFS while reducing exposure to lung irradiation. Therapy was adjusted based on lung nodule response and tumor-specific loss of heterozygosity at 1p and 16q.[266][Level of evidence C2]
Regimen M has a higher potential for late effects (increased risk of secondary leukemias and risk of infertility related to a cumulative dose of cyclophosphamide of 8.8 g/m2).
Based on the European experience, the COG AREN0533 (NCT00379340) study applied a new strategy for patients with FH Wilms tumor and isolated lung metastases to improve EFS while reducing exposure to lung irradiation. Therapy was adjusted based on lung nodule response and tumor-specific loss of heterozygosity at 1p and 16q.[266][Level of evidence C2]
COG showed that initial lung radiation therapy could be avoided in approximately 40% of patients. OS was excellent; however, there was a trend toward more events than expected (expected, 15% and observed, 20%; P = .052).
Although fewer patients were spared pulmonary radiation when treated in the COG trial than in the European trials, it is important to note several differences between the studies and why the studies cannot be directly compared.[266,281] Patients in Europe receive a more dose-dense regimen of dactinomycin and doxorubicin before their pulmonary metastases are reevaluated than do patients in North America (135 ug/kg dactinomycin and 100 mg/m2 doxorubicin in Europe, compared with 45 ug/kg dactinomycin and 45 mg/m2 of doxorubicin in North America). European studies allow lung radiation therapy to be omitted for patients with a complete remission achieved by chemotherapy or pulmonary metastasectomy, whereas radiation therapy was only omitted in the United States for patients with a complete remission using chemotherapy alone. Imaging studies were not centrally reviewed in the European studies, whereas they were in the United States, and the definition of complete remission may have been more stringent in the AREN0533 (NCT00379340) trial.
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