Current Issues in the Diagnosis and Management of Wilms' Tumor
Current Issues in the Diagnosis and Management of Wilms' Tumor
Dr. Paulino provides an excellent summary of current knowledge about Wilms' tumor and its treatment. He stresses the need to improve treatment for those with aggressive tumors and possibly avoid adjuvant treatment in a subset of patients.
In 1966, Farber espoused adjuvant treatment of children with Wilms' tumor based on the supposition that, in children with Wilms' tumor who died, the tumor must have metastasized already at the time of discovery of the primary tumor. Since that time, essentially all children with Wilms' tumor have received adjuvant chemotherapy, and studies conducted by the National Wilms' Tumor Study Group (NWTSG) and the International Society of Pediatric Oncology (SIOP) have defined treatment protocols that are most efficacious in these children.
The most recent NWTSG trial, NWTS 5, is unique in two respects. First, it will prospectively evaluate several genetic factors for their prognostic implications, which may better define treatment requirements. Second, it has defined a specific cohort of children who will not receive adjuvant therapy. In 1990, Larsen and colleagues reported on a group of children who were treated by surgery alone; these patients were under 2 years of age with small encapsulated tumors weighing less than 550 g with no collecting system invasion. These children have done well, except for one child who developed a meta-chronous lesion in the contralateral kidney, which was subsequently cured.
A recent update of this series, which now numbers 11 patients, shows that these children continue to do well, with no deaths or late recurrences. A review of earlier untreated patients less than 2 years of age with small tumors in the NWTS series has also shown a generally favorable outcome. Clearly, a national prospective study of this approach is needed.
Adequacy of resection is critical, as Dr. Paulino states. Efforts should be made to remove the tumor intact, with adequate sampling of lymph nodes to define lymphatic spread. The incision utilized to resect the tumor depends on its location and size. Although a transverse supraumbilical incision is gen-erally used, in large tumors a thoracoabdominal incision will enhance exposure and facilitate resection without rupture of the often friable tumors. Size alone rarely limits resectability of the tumor.
Even though analysis of NWTS 3 demonstrated that preoperative treatment facilitated surgical resection of unresectable tumors, this should not be construed as support of routine preoperative chemotherapy. Clearly defined indications for utilization of preoperative chemotherapy include: (1) bilateral renal lesions; (2) tumor thrombus in the inferior vena cava above the level of the liver; (3) solitary kidney with tumor; (4) respiratory distress from metastatic disease; and (5) extensive tumor at exploration requiring resection of additional organs. This last criterion is difficult to assess based solely on radiographic imaging and generally requires surgical exploration to define.
Contralateral inspection of the kidney has been recommended by the National Wilms' Tumor Committee based on the finding that a significant number of bilateral lesions (7%) are not detected on preoperative imaging. Although the recent studies by Koo and Goleta Dy have questioned this approach, it must be stressed that their reports are based on a very small number of patients. Complications referable to the contralateral exploration have been extremely rare. Partial nephrectomy has been urged for children with bilateral involvement. In general, however, it has not been successful or recommended for children with unilateral disease. This is due to the fact that most of these children present with a large abdominal mass. The infrequent occurrence of small tumors amenable to partial nephrectomy was well demonstrated in the St. Jude series, in which only 2 of 43 cases seemed appropriate for attempts at partial nephrectomy.
The one exception may be children who are being prospectively evaluated with ultrasound for congenital syndromes associated with Wilms' tumor (eg, hemihypertrophy or Beckwith-Wiedemann syndrome) in whom the tumor is extremely small when found. In this setting, resection of the small primary by a partial nephrectomy will preserve maximum renal parenchyma in children predisposed to developing further tumors. Other studies evaluating pretreatment of children with unilateral tumors have demonstrated that, in most instances, a nephrectomy is still required because of the extensive involvement of the kidney with tumor at presentation.
Relapsed disease will be treated for the first time on protocol in the NWTS 5 study. It is hoped that this study can compile additional information on these children with aggressive recurrent tumors. Certain questions, such as the need for pulmonary radiation therapy in stage IV disease, remain unanswered. The number of children that would be required to assess the need for pulmonary radiation in a randomized fashion is too large to be accrued.
Dr. Paulino concludes that additional information is needed to clarify the role of partial nephrectomy, particularly in children with bilateral tumors, and to identify children who may not require adjuvant therapy. All these issues are being addressed in current studies. Hopefully, continued multi-institutional participation in these studies will achieve adequate patient accrual to resolve these remaining questions.
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