What are the diagnosis and management options for Wilms tumor?

Diagnosis and Management of Wilms Tumor

Diagnosis

Wilms tumor diagnosis requires imaging with ultrasound or CT scan to identify the renal mass, followed by surgical excision or biopsy for histopathological confirmation, with genetic testing strongly recommended to identify predisposition syndromes that guide surveillance and treatment intensity. 1, 2

Initial Diagnostic Workup

• Imaging studies should include abdominal ultrasound as the initial screening modality, followed by CT or MRI for detailed anatomical assessment and staging 2
• Histopathological examination is essential to distinguish favorable histology (90% of cases) from unfavorable histology (anaplastic features), which dramatically impacts prognosis and treatment intensity 1, 2
• Genetic testing for predisposition syndromes (TRIM28, REST, CTR9, DIS3L2, WT1) should be performed as part of comprehensive evaluation, particularly in patients with epithelial-predominant histology (86% harbor TRIM28 variants) or bilateral tumors 3

Screening in High-Risk Populations

• Children with WT1 pathogenic variants (Denys-Drash syndrome, WAGR syndrome) require abdominal ultrasound every 3 months from birth through age 7 years 4
• Patients with overgrowth syndromes (Beckwith-Wiedemann syndrome) require renal ultrasound every 3 months until the 7th birthday 4
• DICER1 syndrome carriers require biannual abdominal ultrasound until age 8, then annually thereafter, as Wilms tumor has been reported up to age 13 years in this population 4

Management

All patients with Wilms tumor must be managed by a multidisciplinary team with pediatric oncology expertise, with treatment consisting of surgery combined with risk-stratified chemotherapy and radiation therapy to achieve the current >90% survival rate. 2, 5

Surgical Approach

The major difference between international protocols is timing of surgery:

• North American approach (COG/NWTSG) recommends primary nephrectomy before chemotherapy to obtain accurate histological staging and guide subsequent therapy 1, 2, 5
• European approach (SIOP) recommends preoperative chemotherapy followed by delayed nephrectomy to reduce tumor size and surgical complications 1

Surgical principles include:

• Radical nephrectomy with en bloc removal of tumor, kidney, ureter, and perirenal fat without tumor spillage 5
• Nephron-sparing surgery may be considered in bilateral disease or patients with predisposition syndromes at risk for metachronous tumors 1, 2
• Careful lymph node sampling for accurate staging 5
• Avoidance of tumor rupture, which upstages disease and necessitates more intensive therapy 5

Chemotherapy

Actinomycin D is FDA-approved for Wilms tumor as part of multi-phase combination chemotherapy 6:

• Recommended dose: 45 mcg/kg intravenously once every 3 to 6 weeks for up to 26 weeks as part of multi-agent regimen 6
• Standard regimens combine actinomycin D with vincristine for favorable histology, with addition of doxorubicin for higher-stage or unfavorable histology disease 6, 2
• Treatment duration and intensity are stratified by stage (I-IV) and histology (favorable vs. unfavorable) 2

Radiation Therapy

• Stage I-II favorable histology: No radiation therapy required 2
• Stage III favorable histology: Flank radiation (10.8 Gy) indicated for residual disease, lymph node involvement, or tumor spillage 2
• Stage IV or unfavorable histology: Radiation therapy to primary site and metastatic sites as indicated 2
• Critical caveat: Lack of adequate radiotherapy facilities significantly compromises outcomes, as demonstrated in resource-limited settings where survival dropped to 35.6% 7

Risk Stratification

Treatment intensity must be tailored based on:

• Stage (I-IV based on extent of disease) 2
• Histology (favorable vs. unfavorable/anaplastic) - unfavorable histology carries significantly worse prognosis 1, 2, 7
• Genetic factors: Patients with TRIM28, REST, or CTR9 variants may require modified surveillance 3
• Bilateral disease: Requires careful consideration as 4-year event-free survival is only 43.8% with overall survival of 55.2% 3

Surveillance After Treatment

Post-treatment surveillance is critical, especially for patients with genetic predisposition:

• Patients with genetic syndromes require continued renal ultrasound surveillance every 3 months until age 8 years 3
• All patients require monitoring for recurrence and second malignancies, as risk is elevated in those with predisposition syndromes 3
• Long-term follow-up should address treatment-related toxicities including cardiac dysfunction (from doxorubicin), renal insufficiency, and secondary malignancies 2

Common Pitfalls

• Late presentation (mean symptom duration 4.9 months in some series) results in larger tumors (mean 1040g) and worse outcomes 7
• Treatment abandonment: Non-compliance with chemotherapy dramatically reduces survival from 73.7% to 35.6% 7
• Inadequate staging: Failure to properly stage disease leads to under- or over-treatment 5
• Tumor spillage during surgery: Upstages disease and necessitates additional radiation therapy 5