Additional Treatment Considerations
        Stage I Wilms tumor
        Stage IV Wilms tumor
        Stage V Wilms tumor
        Inoperable Wilms tumors

Table 1 describes the standard chemotherapy regimens used to treat Wilms tumor.

Table 2 provides an overview of the standard treatment based on published results for all stages of Wilms tumor and survival information.

It may be possible to treat a subset of stage I Wilms tumor patients with surgery alone without chemotherapy. The Children’s Oncology Group is addressing this question in a large study. In the National Wilms Tumor Study-5 (NWTS-5) trial, for children older than 2 years at diagnosis with stage I favorable histology (FH) Wilms tumors that weigh more than 550 g, results suggested the costs of the therapy may outweigh the benefits.[14] In NWTS-5 these patients did not receive any postoperative chemotherapy or radiation. The study was designed conservatively based on the assumption that only 50% of the patients with recurrence could be successfully salvaged. The 3-year interim analysis showed a 2-year event–free survival (EFS) of 86.5% which indicated, according to the statistical design, that there was 95% probability that “no treatment” had failed. This part of the study was closed to further accrual and children with recent nephrectomy were advised to receive treatment as per regimen EE-4A (see Table 1). Of the 75 children treated with nephrectomy only prior to closure of the protocol, 11 patients relapsed or developed metachronous disease in the contralateral kidney 0.3 to 2.3 years after diagnosis (median: 4 months, mean: 0.64 years). The sites of relapse were lung (five patients) and operative bed (three patients). Three patients developed disease in the contralateral kidney. The overall survival (OS) of these 11 relapsed patients was 91%. The salvage rate in this cohort of patients from NWTS-5 was much higher (91%) than the postulated rate of 50%, a finding that supports a less conservative approach.[14]

For patients with stage IV FH Wilms tumor, the role of pulmonary irradiation has been examined retrospectively (based on chest x-ray results) and is being examined prospectively (based on computerized tomography scan results) to identify clinical and radiological features in patients that suggest that radiation can be omitted in certain subsets. Investigators in the United Kingdom reviewed outcomes in children with stage IV Wilms tumor with pulmonary metastases at diagnosis and the factors that contributed to the decision to withhold pulmonary radiation. Patients who underwent pulmonary irradiation had a 9-year EFS of 79% versus 53% in patients who did not, although there was no difference in OS. Pulmonary radiation decreased the chance of lung relapse (8% vs 23%). No consistent features could be identified to aid in the selection of patients who could safely avoid pulmonary irradiation.[15]

The treatment of children with bilateral Wilms tumor must be individualized. The goals of therapy are to eradicate all tumor and to preserve as much normal renal tissue as possible with the hope of decreasing the risk of chronic renal failure among these children.[5,6] Studies demonstrate no difference in survival for children who undergo initial bilateral biopsy followed by chemotherapy and then surgical resection compared with patients who have initial resection followed by chemotherapy. Initially, patients should undergo bilateral renal biopsies with staging of each kidney. Primary tumor excision should not be attempted, but patients should be given preoperative chemotherapy. Initial treatment is with regimen EE-4A (see Table 1) if the renal tumors are of FH and not more extensive than stage II. Those with higher stage and FH disease should receive regimen DD-4A (see Table 1), and those with anaplastic histology (AH) should receive regimen I (see Table 1). Following 6 weeks of chemotherapy, the patient should be reassessed. If serial imaging studies show no further reduction in tumor, a second-look surgical procedure should be performed (partial nephrectomy or wedge excision) if negative margins can be obtained; otherwise, sequential biopsies should be done to establish the reason for failure to respond. This approach will identify patients with anaplasia or differentiation, select them for early surgery, and define the intensity of chemotherapy to be administered.[7,8] Chemotherapy and/or radiation therapy following the second-look operation is dependent on the response to initial therapy, with more aggressive therapy required for patients with inadequate response to initial therapy observed at the second procedure.[7,9-13]

Renal transplantation for children with Wilms tumor is usually delayed until 1 to 2 years have passed without evidence of malignancy.[16] Similarly, renal transplantation for children with Denys-Drash syndrome and Wilms tumor, all of whom require bilateral nephrectomy, is generally delayed 1 to 2 years after completion of treatment for the tumor.[16]

Approximately 10% of patients with bilateral tumors have AH and may benefit from more aggressive chemotherapy and radiation therapy, and an aggressive surgical approach at the second-look operation.[2]

Patients who have tumors with caval extension above the hepatic veins or that are so massive that their surgeons consider the risk of initial surgical removal too great should be biopsied and treated with preoperative chemotherapy.[12,17] If surgery is performed on a patient with caval or atrial extension, care should be taken to ensure that appropriate resources are available for pediatric cardiopulmonary bypass.[18,19] On the NWTS-5, these patients were treated after biopsy by initial chemotherapy with vincristine and dactinomycin with or without doxorubicin. If no reduction in tumor size occurred after using three drugs, then radiation therapy was used.[20] Surgery was performed as soon as sufficient tumor shrinkage had occurred, generally at week 6 of therapy. If resection of the tumor could not occur at that time, the patient had a second-look procedure to confirm a persistent tumor. Failure of the tumor to shrink could be a result of a predominance of skeletal or benign elements. Patients were subsequently treated as for stage III tumors, which includes postoperative radiation therapy.[21] Because of the 5% to 10% error rate in preoperative diagnosis of renal masses after radiographic assessment, confirmation of the diagnosis by biopsy (which may be performed percutaneously) should be obtained prior to chemotherapy.[12]

References

1. Green DM, Breslow NE, Beckwith JB, et al.: Comparison between single-dose and divided-dose administration of dactinomycin and doxorubicin for patients with Wilms' tumor: a report from the National Wilms' Tumor Study Group. J Clin Oncol 16 (1): 237-45, 1998.  [PUBMED Abstract]
   
   
2. 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]
   
   
3. Green DM, Beckwith JB, Breslow NE, et al.: Treatment of children with stages II to IV anaplastic Wilms' tumor: a report from the National Wilms' Tumor Study Group. J Clin Oncol 12 (10): 2126-31, 1994.  [PUBMED Abstract]
   
   
4. 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]
   
   
5. Montgomery BT, Kelalis PP, Blute ML, et al.: Extended followup of bilateral Wilms tumor: results of the National Wilms Tumor Study. J Urol 146 (2 ( Pt 2)): 514-8, 1991.  [PUBMED Abstract]
   
   
6. Breslow NE, Takashima JR, Ritchey ML, et al.: Renal failure in the Denys-Drash and Wilms' tumor-aniridia syndromes. Cancer Res 60 (15): 4030-2, 2000.  [PUBMED Abstract]
   
   
7. Fuchs J, Wünsch L, Flemming P, et al.: Nephron-sparing surgery in synchronous bilateral Wilms' tumors. J Pediatr Surg 34 (10): 1505-9, 1999.  [PUBMED Abstract]
   
   
8. Shamberger RC, Haase GM, Argani P, et al.: Bilateral Wilms' tumors with progressive or nonresponsive disease. J Pediatr Surg 41 (4): 652-7; discussion 652-7, 2006.  [PUBMED Abstract]
   
   
9. Ritchey ML, Green DM, Thomas PR, et al.: Renal failure in Wilms' tumor patients: a report from the National Wilms' Tumor Study Group. Med Pediatr Oncol 26 (2): 75-80, 1996.  [PUBMED Abstract]
   
   
10. Horwitz JR, Ritchey ML, Moksness J, et al.: Renal salvage procedures in patients with synchronous bilateral Wilms' tumors: a report from the National Wilms' Tumor Study Group. J Pediatr Surg 31 (8): 1020-5, 1996.  [PUBMED Abstract]
    
    
11. Wilms' tumor: status report, 1990. By the National Wilms' Tumor Study Committee. J Clin Oncol 9 (5): 877-87, 1991.  [PUBMED Abstract]
    
    
12. Ritchey ML: The role of preoperative chemotherapy for Wilms' tumor: the NWTSG perspective. National Wilms' Tumor Study Group. Semin Urol Oncol 17 (1): 21-7, 1999.  [PUBMED Abstract]
    
    
13. Zuppan CW, Beckwith JB, Weeks DA, et al.: The effect of preoperative therapy on the histologic features of Wilms' tumor. An analysis of cases from the Third National Wilms' Tumor Study. Cancer 68 (2): 385-94, 1991.  [PUBMED Abstract]
    
    
14. Green DM, Breslow NE, Beckwith JB, et al.: Treatment with nephrectomy only for small, stage I/favorable histology Wilms' tumor: a report from the National Wilms' Tumor Study Group. J Clin Oncol 19 (17): 3719-24, 2001.  [PUBMED Abstract]
    
    
15. Nicolin G, Taylor R, Baughan C, et al.: Outcome after pulmonary radiotherapy in Wilms' tumor patients with pulmonary metastases at diagnosis: a UK Children's Cancer Study Group, Wilms' Tumour Working Group Study. Int J Radiat Oncol Biol Phys 70 (1): 175-80, 2008.  [PUBMED Abstract]
    
    
16. Kist-van Holthe JE, Ho PL, Stablein D, et al.: Outcome of renal transplantation for Wilms' tumor and Denys-Drash syndrome: a report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Transplant 9 (3): 305-10, 2005.  [PUBMED Abstract]
    
    
17. Shamberger RC, Ritchey ML, Haase GM, et al.: Intravascular extension of Wilms tumor. Ann Surg 234 (1): 116-21, 2001.  [PUBMED Abstract]
    
    
18. Thompson WR, Newman K, Seibel N, et al.: A strategy for resection of Wilms' tumor with vena cava or atrial extension. J Pediatr Surg 27 (7): 912-5, 1992.  [PUBMED Abstract]
    
    
19. Ritchey ML, Kelalis PP, Haase GM, et al.: Preoperative therapy for intracaval and atrial extension of Wilms tumor. Cancer 71 (12): 4104-10, 1993.  [PUBMED Abstract]
    
    
20. Green DM, Breslow NE, Evans I, et al.: The effect of chemotherapy dose intensity on the hematological toxicity of the treatment for Wilms' tumor. A report from the National Wilms' Tumor Study. Am J Pediatr Hematol Oncol 16 (3): 207-12, 1994.  [PUBMED Abstract]
    
    
21. Tournade MF, Com-Nougué C, Voûte PA, et al.: Results of the Sixth International Society of Pediatric Oncology Wilms' Tumor Trial and Study: a risk-adapted therapeutic approach in Wilms' tumor. J Clin Oncol 11 (6): 1014-23, 1993.  [PUBMED Abstract]
    
    

Back to Top

< Previous Section  |  Next Section >