Wilms tumor, treatment for which includes surgery (radical or partial nephrectomy), is the fifth most common pediatric malignancy and the most common type of renal tumor in children. The outcome of current treatment for Wilms tumor is an example of success achieved through a multidisciplinary collaboration of the National Wilms' Tumor Study Group (NWTSG) and the Societe Internationale d'Oncologie Pediatrique (SIOP). Note the image below.
Fifty years ago, when Wilms tumor was treated with surgery alone, the survival rate 2 years after nephrectomy was 20%. The introduction of adjuvant radiotherapy raised the survival rate to 50% overall. Owing to the cooperative efforts of oncologists, surgeons, and pathologists and with the introduction of chemotherapy with vincristine, dactinomycin (actinomycin D), and doxorubicin, the overall survival rate since the late 20th century has risen to 90%.
See Wilms Tumor: A Pediatric Oncology Success Story, a Critical Images slideshow, to help identify the clinical features, staging evaluation, prognostic factors, and therapeutic options for this disease.
Wilms tumor arises from the primitive embryonal renal tissue. Grossly, Wilms tumor is typically an intrarenal solid or cystic mass, which may displace and, in rare cases, invade the renal collecting system. The tumor extends into the renal vein in 40% of cases. In very rare cases, it extends into the ureter and down to the bladder, where it may cause hematuria. Wilms tumor is bilateral in 6% of cases. Local invasion is rare and tumor spread is usually through lymphatic and vascular routes.
Surgical Indications and Contraindications
Indications for primary surgical excision of a Wilms tumor include tumors confined to the kidney, extending beyond the kidney but not crossing the midline, and with or without vascular extension. Postchemotherapy excision of the tumor is indicated in patients with bilateral tumors, tumors that extended beyond the midline and have shrunk, and tumors with vascular extension. Surgery alone is not recommended for Wilms tumor, based on the results of the NWTSG-5 study. [1, 2]
Contraindications to primary surgery for Wilms tumor include bilateral tumors and documented metastatic disease. Large tumors that extend beyond the midline, have vascular extension, or both are relative contraindications, since some surgeons elect to obtain tissue via surgical excision, but this may expose patients to increased surgical risks.
According to the NWTSG protocol, the first step in the treatment of Wilms tumor is surgical staging followed by radical nephrectomy, if possible. During the surgical staging procedure, exploration of the contralateral kidney is considered unnecessary because of the diagnostic reliability of current imaging techniques (computed tomography [CT] scanning, magnetic resonance imaging [MRI]).
If imaging studies demonstrate bilateral disease, nephrectomy is not performed, but biopsy specimens are obtained. New protocols in the management of bilateral Wilms tumor are being explored.
The role of partial nephrectomy remains controversial. Although end-stage renal disease after unilateral radical nephrectomy is uncommon (0.25% in the NWTSG trial), preserving healthy renal tissue may prevent this complication, especially in patients with an underlying intrinsic renal disease (eg, WAGR [Wilms tumor, aniridia, genitourinary anomalies, and mental retardation] syndrome, Denys-Drash syndrome). Partial nephrectomy may be feasible in only 10%-15% of patients, as most tumors are too large at initial diagnosis.
The main concern regarding a nephron-sparing procedure is that of local recurrence. The NWTS-4 study showed an 8% local recurrence rate following partial nephrectomy for patients with bilateral disease.  In the presence of bilateral Wilms tumors, solitary kidney, or renal insufficiency, partial nephrectomy is a reasonable consideration.
Laparoscopy has been used for 15 years in pediatric surgical oncology. [4, 5, 6] More recently, several authors have recommended the use of a laparoscopic approach in children with Wilms tumor that has favorable histology and has not spread locally or metastasized. [7, 8] A complete surgical procedure can be performed by laparoscopy when the tumor is small, allowing a first approach to the renal vessels without mobilization of the kidney. In some reports, all the procedures could be completed when the tumor did not cross the lateral edge of the vertebra on the CT scan. [9, 10]
In addition, preliminary but encouraging data indicate that a laparoscopic approach to nephrectomy in benign disease is associated with decreased lengths of hospital stay and analgesic requirements in the pediatric patient. [11, 12, 13, 14] In a child with cancer, faster recovery with a laparoscopic procedure would offer the further benefit of reducing the time required to begin or reinstitute chemo- or radiotherapy postoperatively. 
In recent years, robotic-assisted laparoscopic surgery (RAS) has gained popularity in both adult and pediatric urology. RAS has several advantages over conventional laparoscopic surgery, especially in the enhanced exposure with magnified three-dimensional view and simplification of suturing with the increased degree of freedom and movement of the robotic arm. 
Robotic-assisted nephrectomy is possible in children with Wilms tumor and offers some advantages but should be, at this time, considered experimental. In addition, expense currently limits its use. 
If the tumor is unresectable, biopsies are performed and the nephrectomy is deferred until after chemotherapy, which, in most cases, will shrink the tumor. Contiguous involvement of adjacent organs is frequently overdiagnosed. The overall surgical complication rate for Wilms tumor is approximately 20%. If inferior vena cava (IVC) thrombus is present, preoperative chemotherapy will reduce the cavotomy rate by 50%.
With bilateral Wilms tumor (6% of cases), surgical exploration, biopsy of both sides, and accurate surgical staging (including lymph node biopsy of both sides) are performed. This is followed by 6 weeks of chemotherapy that is appropriate to the stage and histology of the tumor. Reassessment is then performed using imaging studies, followed by definitive surgery with one of the following:
Unilateral radical nephrectomy and partial nephrectomy on the contralateral side
Bilateral partial nephrectomy
Unilateral nephrectomy only, if the response was complete on the opposite side
This approach dramatically reduces the renal failure rate following bilateral Wilms tumor therapy.The overall 2-year survival rate is higher than 80% with this approach, and the nephrectomy rate drops by 50% in patients with bilateral Wilms tumor. Bilateral partial nephrectomy is possible after chemotherapy or, if the tumor on one side responds completely to chemotherapy, with no subsequent need for nephrectomy.
Multimodal therapy (ie, surgery, radiation, chemotherapy) is the key to success when treating Wilms tumor.  The NWTSG recommends preoperative chemotherapy (after initial exploratory laparotomy and biopsy) in the following situations [5, 6, 7] :
Intracaval tumor extension - This occurs in 5% of cases of Wilms tumor and is associated with a 40% rate of surgical complications, even in experienced hands; up-front chemotherapy after staging and biopsy reduces tumor and thrombus size, which account for 25% of surgical complications
Inoperable tumors - Large tumors that involve vital structures make resection difficult; the complication rate is high, and the incidence of tumor spill soilage is also high, although up-front chemotherapy reduces soilage by 50%
Bilateral Wilms tumor
SIOP advocates up-front chemotherapy without previous laparotomy and biopsy. The NWTSG suggests that this approach results in a 1-5% risk of treating a benign disease. 
Chemotherapy without proper surgical staging (eg, staging by means of imaging studies only) may alter the actual initial stage of the disease by the time of surgery and may subsequently alter decisions regarding the adjuvant chemotherapy and radiation therapy, which is based on the surgical staging.
Through a transperitoneal approach, mobilize the ipsilateral colon and enter the Gerota (perinephric) fascia to examine the kidney. In cases of a unilateral tumor, perform a radical nephrectomy if the opposite side is normal. Evaluate the liver, lymph nodes, and peritoneum for metastases. The renal vein and inferior vena cava should be palpated to assess intravascular extension (present in 6% of the cases).
In cases of bilateral disease, excisional biopsy of visible tumor is indicated, followed by re-resection with nephron preservation after chemotherapy. Identify the involved nodes with clips to facilitate postoperative radiation therapy.
Integrity of the surgical specimen is of paramount importance, as tumor spillage has a deleterious impact on prognosis (six-fold increase in local abdominal recurrence).
The NWTSG has published guidelines for postoperative chemotherapy and radiotherapy protocols, based on the surgical staging, as follows:
Stage II with focal anaplasia: Abdominal radiation (1000 cGy); vincristine, actinomycin D, and doxorubicin for 24 wk
Stage III with favorable histology and focal anaplasia: Abdominal radiation (1000 cGy); vincristine, actinomycin D, and doxorubicin for 24 wk
Stage IV with favorable histology or focal anaplasia: Abdominal irradiation according to local stage; bilateral pulmonary irradiation (1200 cGy); trimethoprim/sulfamethoxazole prophylaxis for Pneumocystis jiroveci; c hemotherapy with vincristine, actinomycin D, and doxorubicin
Wilms tumor is designated as stage V if cancer cells are found in both kidneys when the disease is first diagnosed. After bilateral renal biopsies and staging of each kidney, treatment of stage V Wilms tumor varies by stage, as follows:
Stage I or II disease in both kidneys: Vincristine and dactinomycin, preoperatively and for 18 weeks postoperatively
Stage III or IV disease in both kidneys: Vincristine, dactinomycin, and doxorubicin, preoperatively and for 24 weeks postoperatively
Stage III or IV disease in both kidneys with favorable histology: Vincristine, doxorubicin, cyclophosphamide, and etoposide preoperatively and for 24 weeks postoperatively
Bilateral, high-stage tumors with unfavorable histology are associated with a poor prognosis in spite of multimodal therapy.
Follow-up care after treatment must be long (if possible, lifelong), because Wilms tumor may recur after several years. Follow-up consists of chest radiography and abdominal ultrasonography, CT scanning, or MRI every 3 months for the first 2 years, every 6 months for another 2 years, and once every 2 years thereafter.
Outcome and Prognosis
Tumor biomarkers, histology, and stage are the most important prognostic factors in cases of unilateral disease.
With the advent of multimodal therapy, patients with Wilms tumor have a good prognosis; the disease is considered an example of success in cancer therapy. The overall survival rate with Wilms tumor is 90%. Patients with cases that involve diffuse anaplasia and stage III or IV disease that recur despite complex therapy have a much poorer prognosis. However, the addition of newer chemotherapeutic agents, such as cyclophosphamide, ifosfamide, cisplatin, carboplatin, and etoposide, especially the ICE combination (ifosfamide, carboplatin, etoposide), have contributed to significantly increased postrelapse survival rates to 50%-60%. [17, 20, 21]
Complications may include the following:
Small-bowel obstruction (7%)
Wound infection, hernia (4%)
Vascular complications (2%)
Splenic and intestinal injury (1.5%)
Impaired renal function
Bilateral Wilms tumor
Approximately 5% of children with Wilms tumor will have bilateral involvement.  In these patients, the goals of treatment are oncologic control plus preservation of renal parenchyma to ensure sufficient renal function.  Renal insufficiency may adversely affect both overall health outcomes as well as quality of life.  This impact may be especially pronounced in children with bilateral Wilms tumor, who are often younger than their counterparts with unilateral disease and may also be afflicted with syndromes associated with poor renal function at baseline. [25, 26] Bilateral disease is an independent risk factor for the development of renal insufficiency, due in large part to the loss of renal parenchyma.
Overall, about 15% of children with bilateral involvement who were enrolled in National Wilms Tumor Studies 1–4 developed renal insufficiency in the two decades following diagnosis; children with metachronous disease and those with underlying syndromes such as WAGR or Denys–Drash had 50% increased risk of renal failure. In particular, risk was increased in children who had not undergone upfront chemotherapy or initial nephron-sparing surgery. 
Chemotherapy and nephron-sparing surgery (NSS) provide a safe and effective means of providing oncologic control. [27, 28] Current collaborative studies for patients with Wilms tumor aim at optimizing therapy while decreasing morbidity. Although NSS preserves renal parenchyma and thus may prevent renal failure, NSS can be considered a form of treatment questions remain over whether recurrence rates are higher with this approach. 
Using risk stratification based on the molecular profile of the tumor may allow treatment to be tailored for each patient individually. Clinical outcomes may be further improved with promising new cytotoxic agents, such as the camptothecin analogue topotecan. A promising class of chemotherapeutic drugs is the antiangiogenesis agents, which target the vascular endothelial growth factor (VEGF) pathway.