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Wilms Tumor and Other Childhood Kidney Tumors Treatment (PDQ®)

Health Professional Version
Last Modified: 08/15/2014

Treatment of Recurrent Childhood Kidney Tumors

Prognosis, Prognostic Factors, and Risk Categories for Recurrent Wilms Tumor
Treatment of Standard-Risk Relapsed Wilms Tumor
        Surgery, radiation therapy, and chemotherapy
Treatment of High-Risk and Very High-Risk Relapsed Wilms Tumor
        Chemotherapy, surgery, and/or radiation therapy
        HSCT
Treatment of Recurrent Clear Cell Sarcoma of the Kidney
Current Clinical Trials

Patients with recurrent rhabdoid tumor of the kidney, clear cell sarcoma of the kidney, neuroepithelial tumor of the kidney, and renal cell carcinoma should be considered for treatment on available phase I and phase II clinical trials.

Table 8. Treatment Options for Recurrent Childhood Kidney Tumors
Tumor Type Treatment Options 
Standard-risk relapsed Wilms tumorSurgery, radiation therapy, and chemotherapy
High-risk and very high-risk relapsed Wilms tumorChemotherapy, surgery, and/or radiation therapy
Hematopoietic stem cell transplantation
Recurrent clear cell sarcoma of the kidneyChemotherapy, surgery, and/or radiation therapy

Prognosis, Prognostic Factors, and Risk Categories for Recurrent Wilms Tumor

Approximately 15% of patients with favorable-histology (FH) Wilms tumor and 50% of patients with anaplastic Wilms tumor experience recurrence.[1] Historically, the salvage rate for patients with recurrent FH Wilms tumor was 25% to 40%. As a result of modern treatment combinations, the outcome after recurrence has improved up to 60%.[2,3]

A number of potential prognostic features influencing outcome postrecurrence have been analyzed, but it is difficult to separate whether these factors are independent of each other. Also, the following prognostic factors appear to be changing over time as therapy for primary and recurrent Wilms tumor evolves:

  • Anaplastic histology.[4]
  • Advanced tumor stage.[4]
  • Gender: Gender was predictive of outcome, with males faring worse than females.[2,5]

The National Wilms Tumor Study-5 (NWTS-5 [NCT00002611]) showed that time to recurrence and site of recurrence are no longer prognostically significant.[2,5] However, in a Société Internationale d’Oncologie Pédiatrique (SIOP) study, patients who experienced a pulmonary relapse within 12 months of diagnosis had a poorer prognosis (5-year overall survival [OS], 47%) than did patients who experienced a pulmonary relapse 12 months or more after diagnosis (5-year OS, 75%).[6]

On the basis of these results, the following three risk categories have been identified:

  • Standard risk: Patients with FH Wilms tumor who relapse after therapy with only vincristine and/or dactinomycin. These patients are expected to have an event-free survival (EFS) of 70% to 80%.[3] Standard-risk patients experience approximately 30% of recurrences.

  • High risk: Patients with FH Wilms tumor who relapse after therapy with three or more agents. These patients account for 45% to 50% of children with Wilms tumor who relapse and have survival rates in the 40% to 50% range.[3]

  • Very high risk: Patients with recurrent anaplastic or blastemal-predominant Wilms tumor. These patients are expected to have survival rates in the 10% range, and they experience 10% to 15% of all Wilms tumor relapses.[3,7]

Treatment of Standard-Risk Relapsed Wilms Tumor

In children who had small stage I Wilms tumor and were treated with surgery alone, the EFS was 84%. All but one child who relapsed was salvaged with treatment tailored to the site of recurrence.[8,5]

Successful retreatment can be accomplished for Wilms tumor patients whose initial therapy consisted of immediate nephrectomy followed by chemotherapy with vincristine and dactinomycin and who relapse.

Treatment options for standard-risk relapsed Wilms tumor include the following:

  1. Surgery, radiation therapy, and chemotherapy.
Surgery, radiation therapy, and chemotherapy

Evidence (surgery, radiation therapy, and chemotherapy):

  1. Fifty-eight patients were treated on the NWTS-5 (COG-Q9402/NCT00002611) relapse protocol, with surgical excision when feasible, radiation therapy, and alternating courses of vincristine, doxorubicin, and cyclophosphamide; and etoposide and cyclophosphamide.[5]
    • Four-year EFS after relapse was 71%, and OS was 82%.

    • For patients whose site of relapse was only the lungs, the 4-year EFS rate was 68% and the OS rate was 81%.

Treatment of High-Risk and Very High-Risk Relapsed Wilms Tumor

Treatment options for high-risk and very high-risk relapsed Wilms tumor include the following:

  1. Chemotherapy, surgery, and/or radiation therapy.
  2. Hematopoietic stem cell transplantation (HSCT).
Chemotherapy, surgery, and/or radiation therapy

Evidence (chemotherapy, surgery, and/or radiation therapy):

  1. Approximately 50% of unilateral Wilms tumor patients who relapse or progress after initial treatment with vincristine, dactinomycin, and doxorubicin and radiation therapy can be successfully retreated. Sixty patients with unilateral Wilms tumor were treated on the NWTS-5 relapse protocol with alternating courses of cyclophosphamide/etoposide and carboplatin/etoposide, surgery, and radiation therapy.[2][Level of evidence: 2A]
    • The 4-year EFS rate for patients with high-risk Wilms tumor was 42%, and the OS rate was 48%.

    • High-risk patients who relapsed in the lungs only had a 4-year EFS rate of 49% and an OS rate of 53%.

Patients with stage II, stage III, and stage IV anaplastic-histology tumors at diagnosis have a very poor prognosis upon recurrence.[7] The combination of ifosfamide, etoposide, and carboplatin has demonstrated activity in this group of patients, but significant hematologic toxic effects have been observed.[9]

HSCT

High-dose chemotherapy followed by autologous HSCT has been utilized for recurrent high-risk patients.[10-12]

Evidence (HSCT):

  1. An intergroup study of the former Pediatric Oncology Group and the former Children’s Cancer Group used a salvage induction regimen of cyclophosphamide and etoposide (CE) alternating with carboplatin and etoposide (PE) followed by delayed surgery. Disease-free patients with FH tumors were assigned to maintenance chemotherapy with five cycles of alternating CE and PE, and the rest of the patients were assigned to ablative therapy and autologous stem cell rescue. All patients received local radiation therapy.[13]
    • The 3-year survival was 52% for all eligible patients, while the 3-year survival was 64% for the chemotherapy consolidation subgroup and 42% for the autologous stem cell rescue subgroup.

The outcome of autologous stem cell rescue in selected patients is favorable; however, patients with gross residual disease going into transplant do not do as well.[10,12,14] No randomized trials of chemotherapy versus transplant have been reported, and case series suffer from selection bias.

Patients in whom such salvage attempts fail should be offered treatment on available phase I or phase II studies.

Treatment of Recurrent Clear Cell Sarcoma of the Kidney

Clear cell sarcoma of the kidney has been characterized by late relapses. However, in NWTS-5, most relapses occurred within 3 years, and the most common site of recurrence was the brain.[15]

The optimal treatment of relapsed clear cell sarcoma of the kidney has not been established. Treatment of patients with recurrent clear cell sarcoma of the kidney depends on initial therapy and site of recurrence.

Treatment options for recurrent clear cell sarcoma of the kidney include the following:

  1. Chemotherapy, surgery, and/or radiation therapy.

Cyclophosphamide and carboplatin should be considered if not used initially. Patients with recurrent clear cell sarcoma of the kidney involving the brain have responded to treatment with ifosfamide, carboplatin, and etoposide (ICE) coupled with local control consisting of either surgical resection and/or radiation.[16][Level of evidence: 2A]

The use of high-dose chemotherapy followed by stem cell transplant is undefined in patients with recurrent clear cell sarcoma of the kidney.[17]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent Wilms tumor and other childhood kidney tumors. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References
  1. Green DM, Breslow NE, Beckwith JB, et al.: Effect of duration of treatment on treatment outcome and cost of treatment for Wilms' tumor: a report from the National Wilms' Tumor Study Group. J Clin Oncol 16 (12): 3744-51, 1998.  [PUBMED Abstract]

  2. 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 50 (2): 236-41, 2008.  [PUBMED Abstract]

  3. Reinhard H, Schmidt A, Furtwängler R, et al.: Outcome of relapses of nephroblastoma in patients registered in the SIOP/GPOH trials and studies. Oncol Rep 20 (2): 463-7, 2008.  [PUBMED Abstract]

  4. Grundy P, Breslow N, Green DM, et al.: Prognostic factors for children with recurrent Wilms' tumor: results from the Second and Third National Wilms' Tumor Study. J Clin Oncol 7 (5): 638-47, 1989.  [PUBMED Abstract]

  5. 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 48 (5): 493-9, 2007.  [PUBMED Abstract]

  6. Warmann SW, Furtwängler R, Blumenstock G, et al.: Tumor biology influences the prognosis of nephroblastoma patients with primary pulmonary metastases: results from SIOP 93-01/GPOH and SIOP 2001/GPOH. Ann Surg 254 (1): 155-62, 2011.  [PUBMED Abstract]

  7. 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 24 (15): 2352-8, 2006.  [PUBMED Abstract]

  8. Shamberger RC, Anderson JR, Breslow NE, et al.: Long-term outcomes for infants with very low risk Wilms tumor treated with surgery alone in National Wilms Tumor Study-5. Ann Surg 251 (3): 555-8, 2010.  [PUBMED Abstract]

  9. Abu-Ghosh AM, Krailo MD, Goldman SC, et al.: Ifosfamide, carboplatin and etoposide in children with poor-risk relapsed Wilms' tumor: a Children's Cancer Group report. Ann Oncol 13 (3): 460-9, 2002.  [PUBMED Abstract]

  10. Garaventa A, Hartmann O, Bernard JL, et al.: Autologous bone marrow transplantation for pediatric Wilms' tumor: the experience of the European Bone Marrow Transplantation Solid Tumor Registry. Med Pediatr Oncol 22 (1): 11-4, 1994.  [PUBMED Abstract]

  11. Pein F, Michon J, Valteau-Couanet D, et al.: High-dose melphalan, etoposide, and carboplatin followed by autologous stem-cell rescue in pediatric high-risk recurrent Wilms' tumor: a French Society of Pediatric Oncology study. J Clin Oncol 16 (10): 3295-301, 1998.  [PUBMED Abstract]

  12. Campbell AD, Cohn SL, Reynolds M, et al.: Treatment of relapsed Wilms' tumor with high-dose therapy and autologous hematopoietic stem-cell rescue: the experience at Children's Memorial Hospital. J Clin Oncol 22 (14): 2885-90, 2004.  [PUBMED Abstract]

  13. Tannous R, Giller R, Holmes E, et al.: Intensive therapy for high risk (HR) relapsed Wilms' tumor (WT): a CCG-4921/POG-9445 study report. [Abstract] Proceedings of the American Society of Clinical Oncology 19: A2315, 2000. 

  14. Spreafico F, Bisogno G, Collini P, et al.: Treatment of high-risk relapsed Wilms tumor with dose-intensive chemotherapy, marrow-ablative chemotherapy, and autologous hematopoietic stem cell support: experience by the Italian Association of Pediatric Hematology and Oncology. Pediatr Blood Cancer 51 (1): 23-8, 2008.  [PUBMED Abstract]

  15. Seibel NL, Sun J, Anderson JR, et al.: Outcome of clear cell sarcoma of the kidney (CCSK) treated on the National Wilms Tumor Study-5 (NWTS). [Abstract] J Clin Oncol 24 (Suppl 18): A-9000, 502s, 2006. 

  16. Radulescu VC, Gerrard M, Moertel C, et al.: Treatment of recurrent clear cell sarcoma of the kidney with brain metastasis. Pediatr Blood Cancer 50 (2): 246-9, 2008.  [PUBMED Abstract]

  17. Gooskens SL, Furtwängler R, Vujanic GM, et al.: Clear cell sarcoma of the kidney: a review. Eur J Cancer 48 (14): 2219-26, 2012.  [PUBMED Abstract]