EDITORIAL COMMENT
1
stage I disease. 11 The surgical technique used in this subset of children was not specified. Our series and those of others also demonstrate a severely decreased survival rate (10% to 26%) in children with bilateral Wilms tumor and anapla- sia. 1, 9 This finding is associated with the fact that chemo- therapy is less effective in anaplastic tumors. 13 Thus, in the rationale for nephron sparing surgery in this select group of patients is weakened. Perhaps a more aggressive surgical approach would increase survival in this group, although to our knowledge this remains unknown. For more than 3 decades bilateral nephrectomy and trans- plantation in children with bilateral Wilms tumor have been considered a last resort at our institution. 5, 7 Based on our review we consider diffuse anaplasia to be a contraindication to nephron sparing surgery in patients with bilateral Wilms tumor, and we recommend prompt exenterative surgery. Be- fore the identification of unfavorable histology as a poor prognostic factor DeLorimier et al also recommended prompt bilateral nephrectomy, dialysis and transplantation when tumor was not controlled by radiation and chemotherapy. 14 With the identification of an unfavorable histology as a poor prognostic factor Kumar 1 and Blute 11 et al also suggested that renal preservation should be a secondary consideration. CONCLUSIONS Preoperative chemotherapy in patients with bilateral Wilms tumor frequently permits nephron sparing surgery. Our data suggest that in patients with bilateral Wilms tumor who have a good response to initial chemotherapy and a favorable histology a nephron sparing approach has a high likelihood of cure with preservation of renal function. In patients with chemoresistant tumors brachytherapy should be considered for controlling local disease. In those with diffuse anaplasia the goal of nephron sparing treatment should be abandoned. Strong consideration should be given in this select population to immediate radical nephrectomy or bilateral nephrectomy and renal transplantation. REFERENCES 1. Kumar, R., Fitzgerald, R. and Breatnach, F.: Conservative sur- gical management of bilateral Wilms tumor: results of the United Kingdom Children’s Cancer Study Group. J Urol, 160: 1450, 1998. 2. Thoms, W. W., Jr., Goldwein, J. W. and D’Angio, G.: A technique for the use of afterloading 137 Cs brachytherapy in renal- sparing irradiation of bilateral Wilms tumor. Int J Radiat Oncol Biol Phys, 39: 1121, 1997. 3. Duckett, C. P., Zderic, S., Goldwein, J. et al: Brachytherapy for residual intra-renal Wilms’ tumor. Med Pediatr Oncol, 28: 316, 1997. 4. Farber, S.: Chemotherapy in the treatment of leukemia and Wilms’ tumor. JAMA, 198: 826, 1966. 5. Bishop, H. C. and Hope, J. W.: Bilateral Wilms’ tumor. J Pediatr Surg, 1: 476, 1966. 6. D’Angio, G. J., Breslow, N., Beckwith, J. B. et al: Treatment of Wilms’ tumor. Results of the Third National Wilms’ Tumor Study. Cancer, 64: 349, 1989. 7. Bishop, H. C., Tefft, M., Evans, A. E. et al: Survival in bilateral Wilms’ tumor: review of 30 National Wilms’ Tumor Study cases. J Pediatr Surg, 12: 631, 1977. 8. Asch, M. J., Siegal, S., White, L. et al: Prognostic factors and outcome in bilateral Wilms’ tumor. Cancer, 56: 2524, 1985. 9. Montgomery, B. T., Kelalis, P. P., Blute, M. L. et al: Extended followup of bilateral Wilms’ tumor: results of the National Wilms’ Tumor Study. J Urol, 146: 514, 1991. 10. Horwitz, J. R., Ritchey, M. L., Moksness, J. et al: Renal salvage procedures in patients with synchronous bilateral Wilms’ tu- mors: a report from the National Wilms’ Tumor Study Group. J Pediatr Surg, 31: 1020, 1996. 11. Blute, M. L., Kelalis, P. P., Offord, K. P. et al: Bilateral Wilms’ tumor. J Urol, 138: 968, 1987. 12. Shearer, P., Parham, D. M., Fontanesi, J. et al: Bilateral Wilms’ tumor. Review of outcome, associated abnormalities and late effects in 36 pediatric patients treated at a single insitution. Cancer, 72: 1422, 1993. 13. Faria, P., Beckwith, J. B., Mishra, K. et al: Focal versus diffuse anaplasia in Wilms’ tumor: new definitions with prognostic significance: a report from the National Wilms’ Tumor Study Group. Am J Surg Pathol, 20: 909, 1996. 14. DeLorimier, A. A., Belzer, F. O., Kountz, S. L. et al: Treatment of bilateral Wilms’ tumor. Am J Surg, 122: 275, 1971. EDITORIAL COMMENT This important article emphasizes the risk of parenchymal sparing surgery in patients with an anaplastic histology. The authors noted an unusually high incidence of anaplasia in this group of patients with bilateral Wilms tumor, which is an unfavorable histological feature. Anaplasia is a marker of chemoresistance and does not respond to conventional Wilms tumor chemotherapy. The only effec- tive treatment for anaplasia is complete surgical removal, as re- flected by the improved outcome in children with stage I diffuse anaplasia. The recommended protocol for treating bilateral Wilms tumor is to perform biopsy and then begin preoperative therapy. Most bilateral tumors respond to chemotherapy with a reduction in size. In our experience failure of the tumor to shrink is usually not due to anaplasia. In this circumstance we often observe the persistence of mature elements with some skeletal muscle component. We have more often noted anaplasia in tumors that responded to chemother- apy. Clearly some of the chemosensitive portions of the tumors shrink, leaving the anaplastic elements. The International Society of Pediatric Oncologists group reported a similar incidence of anaplasia in patients with bilateral Wilms tumor, suggesting that anaplasia is unaffected by chemotherapy and may be recognized after treatment. In patients known to have anaplasia all attempts at complete surgical excision are warranted. The National Wilms Tumor Study Group favors resection of tumors with a margin of renal tissue rather than enucleation. Enucleation is more likely to be associated with a positive margin, which has a deleterious outcome in patients with anaplasia. The experience in this study confirms that leaving resid- ual anaplasia results in a poor outcome. The discordance rate be- tween initial biopsy and final open surgery is reason for concern. If the initial biopsy shows only favorable tumor, a surgeon may be tempted to proceed with enucleation. In patients with a favorable histology adjuvant therapy results in a good outcome. However, if there is a positive margin with anaplastic cells after enucleation, local recurrence has a dramatic impact on survival. When the sur- geon knows that there is diffuse anaplasia, complete resection of the tumor to provide local tumor control is essential. If the tumor is large or centrally located, approaching the hilum of the kidney, complete nephrectomy should be considered rather than attempts at paren- chymal sparing surgery. It is difficult to assess the role of brachytherapy in bilateral Wilms tumor. In those with anaplasia brachytherapy should not be the first choice. Complete resection of the tumor is needed even if this includes nephrectomy. In patients who do not have an adequate response to chemotherapy surgical resection is usually required. As mentioned, histological examination of the tumor is needed since many of these nonresponding tumors have only mature elements. In select patients with a favorable histology and positive margins brachytherapy may provide effective local tumor control. However, the experience to date is anecdotal. With the small number of patients with bilateral Wilms tumor it is unlikely that a prospective controlled study would be done to determine the role of brachytherapy. This review of a large series of patients with bilateral Wilms tumors at a single institution provides an important take home message regarding the treatment of anaplastic tumors. All surgeons treating children with Wilms tumor should heed this advice. Michael L. Ritchey Division of Pediatric Surgery University of Texas Houston, Texas ROLE OF RENAL SALVAGE PROCEDURES FOR BILATERAL WILMS TUMOR 268
Transcript of EDITORIAL COMMENT
stage I disease.11 The surgical technique used in this subsetof children was not specified. Our series and those of othersalso demonstrate a severely decreased survival rate (10% to26%) in children with bilateral Wilms tumor and anapla-sia.1, 9 This finding is associated with the fact that chemo-therapy is less effective in anaplastic tumors.13 Thus, in therationale for nephron sparing surgery in this select group ofpatients is weakened. Perhaps a more aggressive surgicalapproach would increase survival in this group, although toour knowledge this remains unknown.
For more than 3 decades bilateral nephrectomy and trans-plantation in children with bilateral Wilms tumor have beenconsidered a last resort at our institution.5, 7 Based on ourreview we consider diffuse anaplasia to be a contraindicationto nephron sparing surgery in patients with bilateral Wilmstumor, and we recommend prompt exenterative surgery. Be-fore the identification of unfavorable histology as a poorprognostic factor DeLorimier et al also recommended promptbilateral nephrectomy, dialysis and transplantation whentumor was not controlled by radiation and chemotherapy.14
With the identification of an unfavorable histology as a poorprognostic factor Kumar1 and Blute11 et al also suggestedthat renal preservation should be a secondary consideration.
CONCLUSIONS
Preoperative chemotherapy in patients with bilateralWilms tumor frequently permits nephron sparing surgery.Our data suggest that in patients with bilateral Wilms tumorwho have a good response to initial chemotherapy and afavorable histology a nephron sparing approach has a highlikelihood of cure with preservation of renal function. Inpatients with chemoresistant tumors brachytherapy shouldbe considered for controlling local disease. In those withdiffuse anaplasia the goal of nephron sparing treatmentshould be abandoned. Strong consideration should be givenin this select population to immediate radical nephrectomy orbilateral nephrectomy and renal transplantation.
REFERENCES
1. Kumar, R., Fitzgerald, R. and Breatnach, F.: Conservative sur-gical management of bilateral Wilms tumor: results of theUnited Kingdom Children’s Cancer Study Group. J Urol, 160:1450, 1998.
2. Thoms, W. W., Jr., Goldwein, J. W. and D’Angio, G.: A techniquefor the use of afterloading 137Cs brachytherapy in renal-sparing irradiation of bilateral Wilms tumor. Int J RadiatOncol Biol Phys, 39: 1121, 1997.
3. Duckett, C. P., Zderic, S., Goldwein, J. et al: Brachytherapy forresidual intra-renal Wilms’ tumor. Med Pediatr Oncol, 28:316, 1997.
4. Farber, S.: Chemotherapy in the treatment of leukemia andWilms’ tumor. JAMA, 198: 826, 1966.
5. Bishop, H. C. and Hope, J. W.: Bilateral Wilms’ tumor. J PediatrSurg, 1: 476, 1966.
6. D’Angio, G. J., Breslow, N., Beckwith, J. B. et al: Treatment ofWilms’ tumor. Results of the Third National Wilms’ TumorStudy. Cancer, 64: 349, 1989.
7. Bishop, H. C., Tefft, M., Evans, A. E. et al: Survival in bilateralWilms’ tumor: review of 30 National Wilms’ Tumor Studycases. J Pediatr Surg, 12: 631, 1977.
8. Asch, M. J., Siegal, S., White, L. et al: Prognostic factors andoutcome in bilateral Wilms’ tumor. Cancer, 56: 2524, 1985.
9. Montgomery, B. T., Kelalis, P. P., Blute, M. L. et al: Extendedfollowup of bilateral Wilms’ tumor: results of the NationalWilms’ Tumor Study. J Urol, 146: 514, 1991.
10. Horwitz, J. R., Ritchey, M. L., Moksness, J. et al: Renal salvageprocedures in patients with synchronous bilateral Wilms’ tu-mors: a report from the National Wilms’ Tumor Study Group.J Pediatr Surg, 31: 1020, 1996.
11. Blute, M. L., Kelalis, P. P., Offord, K. P. et al: Bilateral Wilms’tumor. J Urol, 138: 968, 1987.
12. Shearer, P., Parham, D. M., Fontanesi, J. et al: Bilateral Wilms’tumor. Review of outcome, associated abnormalities and lateeffects in 36 pediatric patients treated at a single insitution.Cancer, 72: 1422, 1993.
13. Faria, P., Beckwith, J. B., Mishra, K. et al: Focal versus diffuseanaplasia in Wilms’ tumor: new definitions with prognosticsignificance: a report from the National Wilms’ Tumor StudyGroup. Am J Surg Pathol, 20: 909, 1996.
14. DeLorimier, A. A., Belzer, F. O., Kountz, S. L. et al: Treatment ofbilateral Wilms’ tumor. Am J Surg, 122: 275, 1971.
EDITORIAL COMMENT
This important article emphasizes the risk of parenchymal sparingsurgery in patients with an anaplastic histology. The authors notedan unusually high incidence of anaplasia in this group of patientswith bilateral Wilms tumor, which is an unfavorable histologicalfeature. Anaplasia is a marker of chemoresistance and does notrespond to conventional Wilms tumor chemotherapy. The only effec-tive treatment for anaplasia is complete surgical removal, as re-flected by the improved outcome in children with stage I diffuseanaplasia.
The recommended protocol for treating bilateral Wilms tumor is toperform biopsy and then begin preoperative therapy. Most bilateraltumors respond to chemotherapy with a reduction in size. In ourexperience failure of the tumor to shrink is usually not due toanaplasia. In this circumstance we often observe the persistence ofmature elements with some skeletal muscle component. We havemore often noted anaplasia in tumors that responded to chemother-apy. Clearly some of the chemosensitive portions of the tumorsshrink, leaving the anaplastic elements. The International Society ofPediatric Oncologists group reported a similar incidence of anaplasiain patients with bilateral Wilms tumor, suggesting that anaplasia isunaffected by chemotherapy and may be recognized after treatment.
In patients known to have anaplasia all attempts at completesurgical excision are warranted. The National Wilms Tumor StudyGroup favors resection of tumors with a margin of renal tissue ratherthan enucleation. Enucleation is more likely to be associated with apositive margin, which has a deleterious outcome in patients withanaplasia. The experience in this study confirms that leaving resid-ual anaplasia results in a poor outcome. The discordance rate be-tween initial biopsy and final open surgery is reason for concern. Ifthe initial biopsy shows only favorable tumor, a surgeon may betempted to proceed with enucleation. In patients with a favorablehistology adjuvant therapy results in a good outcome. However, ifthere is a positive margin with anaplastic cells after enucleation,local recurrence has a dramatic impact on survival. When the sur-geon knows that there is diffuse anaplasia, complete resection of thetumor to provide local tumor control is essential. If the tumor is largeor centrally located, approaching the hilum of the kidney, completenephrectomy should be considered rather than attempts at paren-chymal sparing surgery.
It is difficult to assess the role of brachytherapy in bilateral Wilmstumor. In those with anaplasia brachytherapy should not be the firstchoice. Complete resection of the tumor is needed even if this includesnephrectomy. In patients who do not have an adequate response tochemotherapy surgical resection is usually required. As mentioned,histological examination of the tumor is needed since many of thesenonresponding tumors have only mature elements. In select patientswith a favorable histology and positive margins brachytherapy mayprovide effective local tumor control. However, the experience to date isanecdotal. With the small number of patients with bilateral Wilmstumor it is unlikely that a prospective controlled study would be done todetermine the role of brachytherapy.
This review of a large series of patients with bilateral Wilmstumors at a single institution provides an important take homemessage regarding the treatment of anaplastic tumors. All surgeonstreating children with Wilms tumor should heed this advice.
Michael L. RitcheyDivision of Pediatric SurgeryUniversity of TexasHouston, Texas
ROLE OF RENAL SALVAGE PROCEDURES FOR BILATERAL WILMS TUMOR268
