Surgery for Wilms Tumor

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Overview

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.



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Gross nephrectomy specimen shows a Wilms tumor pushing the normal renal parenchyma to the side.

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.

Anatomy

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

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.

Surgical Approach

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.[3] 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.

Partial nephrectomy

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).[4] 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.[5] In the presence of bilateral Wilms tumors, solitary kidney, or renal insufficiency, partial nephrectomy is a reasonable consideration.

Laparoscopic Nephrectomy

Laparoscopy has been used for 15 years in pediatric surgical oncology.[6, 7, 8, 9] 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.[10, 11] 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.[12, 13]

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.[14, 15, 16, 17] 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.[18]

Robotic nephrectomy

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.[19]

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.[17]

Preoperative Details

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:

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.[6, 20] The NWTSG recommends preoperative chemotherapy (after initial exploratory laparotomy and biopsy) in the following situations[7, 8, 10] :

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.[11]

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.

Intraoperative Details

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).

Postoperative Details

The NWTSG has published guidelines for postoperative chemotherapy and radiotherapy protocols, based on the surgical staging, as follows:

A study by Pritchard-Jones et al on 583 children from 251 hospitals in 26 countries aimed to assess whether doxorubicin can be omitted safely from chemotherapy for stage II-III, histological intermediate-risk Wilms' tumor in order to avoid doxorubicin-related cardiotoxicity effects. The study concluded that doxorubicin does not need to be included in treatment of stage II-III intermediate risk Wilms' tumour when the histological response to preoperative chemotherapy is incorporated into the risk stratification.[21]

Stage V

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:

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.

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%.[22, 25, 26]

Complications may include the following:

Bilateral Wilms tumor

Approximately 5% of children with Wilms tumor will have bilateral involvement.[27] In these patients, the goals of treatment are oncologic control plus preservation of renal parenchyma to ensure sufficient renal function.[28] Renal insufficiency may adversely affect both overall health outcomes as well as quality of life.[29] 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.[30, 31] 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.[28]

Chemotherapy and nephron-sparing surgery (NSS) provide a safe and effective means of providing oncologic control.[32, 33] 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.[34]

Future considerations

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.

What is Wilms tumor?What is the anatomy of Wilms tumor?When is surgery indicated in the treatment of Wilms tumor?What are the contraindications to surgery for the treatment of Wilms tumor?What is the role of radical nephrectomy in the treatment of Wilms tumor?What is the role of partial nephrectomy in the treatment of Wilms tumor?What is the role of laparoscopic nephrectomy in the treatment of Wilms tumor?What is the role of robotic-assisted laparoscopic surgery (RAS) in the treatment of Wilms tumor?How are unresectable Wilms tumors treated?How are bilateral Wilms tumors treated?What is the role of chemotherapy in the treatment of Wilms tumor?How is radical nephrectomy performed for the treatment of Wilms tumor?What are the NWTSG guidelines on postoperative chemotherapy and radiotherapy for Wilms tumor?What is a stage V Wilms tumor?What is included in the long-term monitoring of Wilms tumor?What is the prognosis of Wilms tumor?What is the prognosis of bilateral Wilms tumor?Which treatments are under investigation for Wilms tumor?

Author

Tunc Ozan, MD, Assistant Professor of Urology, Chief of Pediatric Urology Division, Department of Urology, Firat University School of Medicine, Turkey

Disclosure: Nothing to disclose.

Coauthor(s)

Marc Cendron, MD, Associate Professor of Surgery, Harvard School of Medicine; Consulting Staff, Department of Urological Surgery, Children's Hospital Boston

Disclosure: Nothing to disclose.

Pablo Gomez, III, MD, Fellow in Pediatric Urology, Children's Hospital Boston, Harvard Medical School

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Bradley Fields Schwartz, DO, FACS, Professor of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Southern Illinois University School of Medicine

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: AUA Journal of Urology<br/>Serve(d) as a speaker or a member of a speakers bureau for: Cook Medical; Olympus, .

Additional Contributors

Leonard Gabriel Gomella, MD, FACS, The Bernard W Godwin Professor of Prostate Cancer Chairman, Department of Urology, Associate Director of Clinical Affairs, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Disclosure: Received consulting fee from GSK for consulting; Received honoraria from Astra Zeneca for speaking and teaching; Received consulting fee from Watson Pharmaceuticals for consulting.

Acknowledgements

Dan Theodorescu, MD, PhD Paul A Bunn Professor of Cancer Research, Professor of Surgery and Pharmacology, Director, University of Colorado Comprehensive Cancer Center

Dan Theodorescu, MD, PhD is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Urological Association, Medical Society of Virginia, Society for Basic Urologic Research, and Society of Urologic Oncology

Disclosure: Key Genomics Ownership interest Co-Founder-50% Stock Ownership; KromaTiD, Inc Stock Options Board membership

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Gross nephrectomy specimen shows a Wilms tumor pushing the normal renal parenchyma to the side.

CT scan in a patient with a right-sided Wilms tumor with favorable histology.

CT scan of child with a stage IV Wilms tumor with favorable histology. Note the bilateral pulmonary metastases.

Gross nephrectomy specimen shows a Wilms tumor pushing the normal renal parenchyma to the side.