Treatment Option Overview
Because of the relative rarity of this tumor, all patients with Wilms tumor should be considered for entry into a clinical trial. Treatment planning by a multidisciplinary team of cancer specialists (pediatric surgeon or pediatric urologist, pediatric radiation oncologist, and pediatric oncologist) with experience treating Wilms tumor is required to determine and implement optimum treatment.
The majority of the randomized clinical studies for treatment of children with Wilms tumor have been conducted by two large clinical groups. The National Wilms Tumor Study (NWTS) Group, which is now part of the Children’s Oncology Group (COG), has established standard treatment for Wilms tumor in North America, which consists of initial surgery followed by chemotherapy and, in some patients, radiation therapy.[1-3] The Société Internationale d’Oncologie Pédiatrique (SIOP) is a European consortium. There are differences between the two groups that affect staging and classification. The SIOP trials provide preoperative chemotherapy before definitive resection. This statement will focus on the NWTS (now COG Renal Tumor Committee) results and studies. The major treatment conclusions of the National Wilms Tumor Studies (NWTS 1–5) are as follows:
- Routine, postoperative radiation therapy of the flank is not necessary for children with stage I tumors or stage II tumors with favorable histology (FH) when postnephrectomy combination chemotherapy consisting of vincristine and dactinomycin is administered.
- The prognosis for patients with stage III FH is best when treatment includes: (a) dactinomycin, vincristine, doxorubicin, and 10.8 Gy of radiation therapy to the flank; or (b) dactinomycin, vincristine, and 20 Gy of radiation therapy to the flank.
- The addition of cyclophosphamide to the combination of vincristine, dactinomycin, and doxorubicin does not improve prognosis for patients with stage IV FH tumors.
- A single-dose of dactinomycin per course (stages I–II FH, stage I anaplastic, stage III FH, stages III–IV, or stages I–IV clear cell sarcoma of the kidney) is equivalent to the divided-dose courses, results in the same event-free survival, achieves greater dose intensity, and is associated with less toxicity and expense.
- Eighteen weeks of therapy is adequate for patients with stage I FH whereas other patients can be treated with 6 months of therapy instead of 15 months.[1,4-7]
- Tumor-specific loss of heterozygosity for combined 1p and 16q predicts recurrence of FH Wilms tumor.
- About 2% of Wilms tumors have ureteral involvement. Presence of gross hematuria, nonfunctioning kidney, or hydronephrosis suggests the tumor may extend into the ureter and cystoscopy is recommended. En bloc resection to avoid tumor spill is recommended.
Operative principles have evolved from NWTS trials. The most important role for the surgeon is to ensure complete tumor removal without rupture and perform an assessment of the extent of disease. Radical nephrectomy and lymph node sampling via a transabdominal or thoracoabdominal incision is the procedure of choice. A flank incision should not be performed because of the limited exposure it provides. For patients with resectable tumors, preoperative or intraoperative biopsy should not be performed. Routine exploration of the contralateral kidney is not necessary if technically adequate imaging studies do not suggest a bilateral process. If the initial imaging studies are suggestive of bilateral kidney involvement and depending on the size of the tumor, biopsy or wedge resection may be performed. Alternatively, the contralateral kidney should be explored to rule out bilateral involvement. This should be done prior to nephrectomy since the diagnosis of bilateral disease would dramatically alter the approach.
Partial nephrectomy remains controversial and is not recommended except for children with bilateral tumors, children with a solitary kidney, or rare cases of horseshoe kidney. However, partial nephrectomy has been suggested for Wilms tumor in infants with Denys-Drash or Frasier syndrome in order to delay the need for dialysis.; [Level of evidence: 3iiB] Also, some children who are predisposed to bilateral tumors who have very small tumors detected by ultrasound screening may be considered for partial nephrectomy to preserve renal tissue. In North America, renal-sparing partial nephrectomy of unilateral Wilms tumor following administration of chemotherapy to shrink the tumor mass is considered investigational.[14,15]
Hilar, periaortic, iliac, and celiac lymph node sampling is mandatory even if the nodes appear normal.[10,16] Furthermore, any suspicious node basin should be sampled. Margins of resection, residual tumor, and any suspicious node basins should be marked with titanium clips. Resection of contiguous organs is rarely indicated and there is an increased incidence of complications occurring in more extensive resections involving removal of additional organs beyond the diaphragm and adrenal gland. This has led to the recommendation in current COG protocols that these patients should be considered for initial biopsy, neoadjuvant chemotherapy, and then secondary resection. Pathologically, Wilms tumor rarely invades adjacent organs. Primary resection of liver metastasis is not recommended. Wilms tumor arising in a horseshoe kidney is rare and accurate preoperative diagnosis is important in planning the operative approach. Primary resection is possible in most cases. Inoperable cases can usually be resected after chemotherapy.
- Metachronous bilateral Wilms tumor.
- Wilms tumor in a solitary kidney.
- Extension of tumor thrombus above the level of the hepatic veins.
- Tumor involves contiguous structures whereby the only means of removing the kidney tumor requires removal of the other structures (e.g., spleen, pancreas, colon but excluding the adrenal gland).
- Pulmonary compromise due to extensive pulmonary metastases.
Patients with massive, nonresectable unilateral tumors, bilateral tumors, or venacaval tumor thrombus extending above the hepatic veins are candidates for preoperative chemotherapy because of the risk of initial surgical resection.[10,17,20,21] Preoperative chemotherapy should follow a biopsy, except in the setting of bilateral disease (COG-AREN0534). The biopsy may be performed percutaneously through a flank approach.[24-29] Preoperative chemotherapy should include doxorubicin in addition to vincristine and dactinomycin unless there is anaplastic histology present, which then includes treatment with other agents. The chemotherapy generally makes tumor removal easier because of the decreased size and vascular supply of the tumor and may reduce the frequency of surgical complications.[17,20,29-31] Postoperative radiation therapy to the tumor bed is required when a biopsy is performed or in the setting of local tumor stage III.
Newborns and all infants younger than 12 months require a reduction in chemotherapy doses to 50% of those given to older children. This reduction diminishes toxic effects reported in children in this age group enrolled in NWTS studies while maintaining an excellent overall outcome. Liver function tests in children with Wilms tumor should be monitored closely during the early course of therapy based on hepatic toxic effects (sinusoidal obstructive syndrome, previously called veno-occlusive disease) reported in those patients.[34,35] Dactinomycin should not be administered during radiation therapy. Patients who develop renal failure while on therapy can continue receiving chemotherapy with vincristine, dactinomycin, and doxorubicin. Vincristine and doxorubicin can be given at full doses; however, dactinomycin is associated with severe neutropenia. Reductions in dosing these agents may not be necessary, but accurate pharmacologic and pharmacokinetic studies are needed while the patient is receiving the therapy.[36,37]
Children treated for Wilms tumor are at increased risk for developing second malignant neoplasms. Congestive heart failure has been shown to be a risk in children treated with doxorubicin with the degree of risk influenced by cumulative doxorubicin dose, radiation to the heart, and gender (females are at increased risk). Efforts, therefore, have been aimed toward reducing the intensity of therapy when possible. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for a full discussion of the late effects of cancer treatment in children and adolescents.)
As mentioned previously, clear cell sarcoma of the kidney, rhabdoid tumor of the kidney, neuroepithelial tumor of the kidney, and cystic partially-differentiated nephroblastoma are childhood renal tumors unrelated to Wilms tumor. Because of their renal location, they have been treated on clinical trials developed by the NWTS Group. The approach to their treatment, however, is distinctive from that of Wilms tumor, and requires timely and accurate diagnosis by a pathologist and pediatric oncologist with experience with these types of renal tumors.References
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