Surgery for Wilms Tumor 

Wilms tumor, treatment for which includes surgery (radical and/or partial nephrectomy), is the fifth most common pediatric malignancy and the most common type of renal tumor in children. The treatment used to treat 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). Fifty years ago, 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%.

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.

Indications

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

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.

Radical nephrectomy

According to the NWTSG protocol, the first step in the treatment of Wilms tumor is surgical staging followed by radical nephrectomy, if possible.

Begin the abdominal exploration through a transverse incision. The kidney is explored by mobilizing the ipsilateral colon and opening the Gerota fascia. Exploration of the contralateral kidney is currently not recommended because of the improvement in imaging techniques (computed tomography [CT] scanning, magnetic resonance imaging [MRI]). If bilateral disease is diagnosed, nephrectomy is not performed, but biopsy specimens are obtained. New protocols in the management of bilateral Wilms tumor are being explored. If the disease is unilateral, radical nephrectomy and regional lymph node dissection or sampling are performed.

Partial nephrectomy

The role of partial nephrectomy remains controversial. Although end-stage renal disease after unilateral radical nephrectomy is uncommon (0.25% in NWTSG trial), preserving healthy renal tissue may prevent this complication, especially in patients with an underlying intrinsic renal disease (eg, WAGR 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.^[3] In the presence of bilateral Wilms tumors, solitary kidney, or renal insufficiency, partial nephrectomy is a reasonable consideration.

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 (1) unilateral radical nephrectomy and partial nephrectomy on the contralateral side; (2) bilateral partial nephrectomy; and (3) 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.

Chemotherapy

Multimodal therapy (ie, surgery, radiation, chemotherapy) is the key to success when treating Wilms tumor.^[4] 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.^[8]

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, enter the Gerota (perinephric fascia) 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 IVC 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 (6-fold increase in local abdominal recurrence).

Postoperative chemotherapy and radiotherapy protocols are based on the surgical staging and follow the guidelines of the NWTSG.

Stage I favorable histology and unfavorable histology or stage II favorable histology includes the following:

• Nephrectomy
• Postoperative vincristine and actinomycin D (18 wk)

Stage II focal anaplasia or stage III favorable histology and focal anaplasia include the following:

• Nephrectomy
• Abdominal radiation (1000 cGy)
• Vincristine, actinomycin D, and doxorubicin (24 wk)

Stage IV favorable histology or focal anaplasia includes the following:

• Nephrectomy
• Abdominal irradiation according to local stage
• Bilateral pulmonary irradiation (1200 cGy) with sulfamethoxazole and trimethoprim (Bactrim) prophylaxis for Pneumocystis carinii
• Chemotherapy with vincristine, actinomycin D, and doxorubicin

Stage II and stage IV diffuse anaplasia include the following:

• Nephrectomy
• Abdominal irradiation
• Whole lung irradiation for stage IV
• Chemotherapy for 24 months with vincristine, actinomycin D, doxorubicin, etoposide, and cyclophosphamide

Bilateral, high-stage tumors with unfavorable histology are associated with a poor prognosis in spite of multimodal therapy.

Follow-up

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.

Tumor biomarkers, histology, and stage are the most important prognostic factors in cases of unilateral disease.

With the advent of multimodal therapy, the prognosis of Wilms tumor is good, and it is considered an example of success in cancer therapy. The overall survival rate of Wilms tumor is 90%. 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%.^{[9, 10, 11]}

Surgical complications

Complications may include the following:

• Small-bowel obstruction (7%)
• Hemorrhage (6%)
• Wound infection, hernia (4%)
• Vascular complications (2%)
• Splenic and intestinal injury (1.5%)

Future considerations

Using risk stratification based on tumor molecular profile 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.