Current Issues in the Diagnosis and Management of Wilms' Tumor

October 1, 1996

Dr. Paulino has written an excellent review of our present knowledge of Wilms' tumor. Not everyone would agree, however, that ultrasound has replaced the intravenous pyelogram (IVP). The National Wilms' Tumor Study Group (NWTSG) recommends IVP together with real-time ultrasonography as the preoperative imaging studies for the abdomen.[1] The former is used to establish the presence of a functioning opposite kidney and of any congenital abnormality. The latter identifies the presence and status of inferior vena cava thrombi.

Dr. Paulino has written an excellent review of our present knowledgeof Wilms' tumor. Not everyone would agree, however, that ultrasoundhas replaced the intravenous pyelogram (IVP). The National Wilms'Tumor Study Group (NWTSG) recommends IVP together with real-timeultrasonography as the preoperative imaging studies for the abdomen.[1]The former is used to establish the presence of a functioningopposite kidney and of any congenital abnormality. The latteridentifies the presence and status of inferior vena cava thrombi.

As neither CT nor MRI can determine, with certainty, the statusof the opposite kidney, the NWTSG still calls for its mobilizationat laparotomy, as Dr. Paulino notes. He appropriately points outthat those who advocate eliminating exploration of the oppositekidney[2,3] base their recommendation on data from a very smallnumbers of patients, compared with the NWTSG data. The NWTSG,therefore, continues to recommend mobilization of the oppositekidney based on the accuracy and lack of morbidity of this procedure.

National Wilms' Tumor Study 4

As the results of the third National Wilms' Tumor Study (NWTS3) were very good (see the author's Table 2), NWTS 4 (1985 to1994) was designed to attempt to simplify and shorten treatmentfor those considered at low risk, while intensifying treatmentfor those at high risk. Although, in NWTS 3, the addition of cyclophosphamide(Cytoxan, Neosar) to vincristine, dactinomycin (actinomycin D[Cosmegan]), and doxorubicin achieved better results in patientswith stages I to IV anaplastic Wilms' tumor, the numbers wereuneven due to weighing of the randomization (21 patients receivingthree drugs and 12 patients receiving four drugs), and it wasfelt appropriate to continue the randomization into NWTS 4.

For the remainder of the patients (excluding those with rhabdoidtumor of the kidney, who are not included in NWTS 4), the trialaimed to answer two questions: (1) Is pulse-intensive therapy(ie, a single dose of dactinomycin and doxorubicin for patientswith stage III or IV, favorable histology and clear cell sarcoma)more effective than standard therapy (5 days of dactinomycin and3 days of doxorubicin)? (2) What is the optimal duration of therapy(6 vs 15 months)? This issue of therapy duration was tested inall patients except those with stage I, favorable histology andanaplastic tumors.

A simplified version of the schema of NWTS 4 is shown in Figure1. The results, which have been partly published in abstract form,suggest that 2-year survival rates are equivalent with the pulse-intensiveand standard regimens,[4] and that toxicity (particularly hematologic)is less severe for most patients on the pulse-intensive arm.[5]

A recent analysis of NWTS 4 has also shown no demonstrable differencesbetween the 6- and 15-month courses of therapy.[unpublished data,NWTS 4]

Patients with anaplastic tumors (stages II-IV) derived a benefitfrom the addition of cyclophosphamide to dactinomycin, vincristine,and doxorubicin if the tumor histology showed a diffuse pattern.No benefit could be discerned for focal anaplasia, however.[6]

National Wilms' Tumor Study 5

In NWTS 5, which began enrollment in 1995, there are no randomizations.The outline is shown in Table 1, and the radiotherapy regimensare detailed in Table 2. A major objective of the protocol isto determine the prognostic significance of the loss of heterozygosityof chromosomes 16q and 1p. This stems from an analysis of 232patients from NWTS 3 and 4 showing that overall and relapse-freesurvival at 2 years was significantly worse for those with the16q abnormality and was marginally so for those with the 1p abnormality.[7]

Also, as Dr. Paulino discusses, there is evidence that stage Ipatients under 2 years of age with tumors weighing less than 550g may not need further therapy. In NWTS 1, 2, and 3, there wereno differences in disease-free or overall survival in these patientsregardless of the therapy employed.[8] In NWTS 5, therefore, thesepatients will be treated by nephrectomy only.

References:

1. D'Angio GJ, Rosenberg H, Sharples K, et al: Position paper:Imaging methods for primary renal tumors of childhood: Costs versusbenefits. Med Pediatr Oncol 21:205-212, 1993.

2. Koo AS, Koyle MA, Hurwitz RS, et al: The necessity of contralateralsurgical exploration in Wilms' tumor with modern non-invasiveimaging technique: A reassessment. J Urol 144:416-417, 1990.

3. Goleta Dy A, Shaw PJ, Stevens MM: Re: The necessity of contralateralsurgical exploration in Wilms' tumor with modern non-invasiveimaging technique: A reassessment (letter). J Urol 174:171, 1992.

4. Green DM, Breslow N, Beckwith JB, et al: A comparison betweensingle dose and divided dose administration of dactinomycin anddoxorubicin: a report from the National Wilms' Tumor Study Group(abstract). Proc Am Soc Clin Oncol 15:457, 1996.

5. Green DM, Breslow, NE, Evans I, et al: Effect of does intensityof chemotherapy on the hematological toxicity of the treatmentof Wilms tumor. A report from the National Wilms Tumor Study.Am J Pediatr Hematol Oncol 16:207-212, 1994.

6. Green DM, Beckwith JB, Breslow NE, et al: Treatment of childrenwith stages II to IV anaplastic Wilms' tumor: A report from theNational Wilms' Tumor Study Group. J Clin Oncol 12:2126-2131,1994.

7. Grundy PE, Tezerow PE, Breslow NE, et al: Loss of heterozygosityfor chromosomes 16q and 1p in Wilms' Tumors predicts an adverseoutcome. Cancer 54:2331-2333, 1994.

8. Green DM, Breslow NE, Beckwith JB, et al: Treatment outcomesin patients less than 2 years of age with small, stage 1, favorable-histologyWilms' tumor: A report from the National Wilms' Tumor Study. JClin Oncol 11:91-95, 1993.