Wilms' tumor medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sargun Singh Walia M.B.B.S.[2]Shanshan Cen, M.D. [3]

Overview

The mainstay of treatment of wilms tumor is nephrectomy. This is followed by chemotherapy with/without chemotherapy. Chemotherapeutic agent used is chosen based on the histology and stage of the tumor. The duration and dose of the chemotherapy varies depending on the stage and age of the patient .There are two schools of thought as to the best therapy for Wilms' tumor. The National Wilms' Tumor Study (NWTS) and The International Society of Paediatric Oncology(SIOP). Preoperative chemotherapy before nephrectomy is indicated in the situations like synchronous bilateral wilms tumor, wilms tumor in a solitary kidney, inoperable tumor. and pulmonary compromise.

Medical therapy

• The mainstay of treatment of wilms tumor is nephrectomy.
• This is followed by chemotherapy with/without chemotherapy.
• Chemotherapeutic agent used is chosen based on the histology and stage of the tumor.
• Chemotherapeutic agents used are:
  • Dactinomycin
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Etoposide
  • Carboplatin
• The duration and dose of the chemotherapy varies depending on the stage and age of the patient .

Chemotherapy of patient with favourable histology (FH) post nephrectomy:

Stage & Histology	Chemotherapy	Radiation therapy
Stage 1 or 2 without loss of heterozygosity	Vincristine Dactinomycin	Not required
Stage 1 or 2 with LOH 1p and 16q	Vincristine Dactinomycin Doxorubicin	Not requireed
Stage 3 and 4 without LOH 1p and 16q	Vincristine Dactinomycin Doxorubicin	Required
Stage 3 and 4 with LOH 1p and 16q	Vincristine Dactinomycin Doxorubicin Cyclophosphamide Etoposide	Required

This summary focuses on the NWTS (now COG Renal Tumor Committee) results and studies.

The major treatment and study conclusions of NWTS-1 through NWTS-5 (NWTS-1, NWTS-2, NWTS-3, NWTS-4, and NWTS-5) are as follows:

• The prognosis for patients with stage III favourable histology(FH) is best when treatment includes either:
  • Dactinomycin + vincristine + doxorubicin with 10.8 Gy of radiation therapy to the flank.
  • Dactinomycin + vincristine with20 Gy of radiation therapy to the flank.
  • Whole abdominal radiation is indicated for extensive intraperitoneal disease or widespread intraperitoneal tumor spill.
• The addition of cyclophosphamide at the protocol dose (10 mg/kg/d for 3 days every 6 weeks) 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 EFS, achieves greater dose intensity, and is associated with less toxicity and expense.
• Eighteen weeks of therapy is adequate for patients with stage I and II FH, whereas other patients can be treated with 6 months of therapy instead of 15 months.
• Tumor-specific loss of heterozygosity for combined 1p and 16q predicts recurrence of FH Wilms tumor.

There are two schools of thought as to the best therapy for Wilms' tumor.

• The National Wilms' Tumor Study (NWTS)
  • It has been studying this tumor in the United States since 1969.
  • This group recommends surgery as the primary therapy for Wilms' tumor.
  • They have carried out extensive research on this tumor which has been used to guide therapy, as well as to classify tumors into high and low risk groups based on molecular features and to estimate prognosis.

• The International Society of Paediatric Oncology(SIOP)
  • It is followed in Europe.
  • It recommends preoperative chemotherapy to downstage the tumor prior to surgery to reduce the risk of intraoperative rupture of the tumor and dissemination of the malignant cells.
  • A 4 week period of preoperative chemotherapy decreases the risk of intraoperative rupture of the tumor.

Preoperative chemotherapy before nephrectomy is indicated in the following situations:

• Synchronous bilateral Wilms tumor.
• Wilms tumor in a solitary kidney.
• Extension of tumor thrombus in the inferior vena cava 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, or colon but excluding the adrenal gland).
• Inoperable Wilms tumor.
• Pulmonary compromise due to extensive pulmonary metastases.

This image is provided by the National Library of Medicine.

This image is provided by the National Library of Medicine.

This image is provided by the National Library of Medicine.

This image is provided by the National Library of Medicine.

This image is provided by the National Library of Medicine.

Treatment options for stage V and those predisposed to developing bilateral Wilms tumor

• Currently, there is not a standard approach for the treatment of stage V Wilms tumor (bilateral Wilms tumor at diagnosis) and those predisposed to developing Wilms tumor.

• Management of a child with bilateral Wilms tumor is very challenging. The goals of therapy are to eradicate all tumor and to preserve as much normal renal tissue as possible, with the hope of decreasing the risk of chronic renal failure among these children.