What is the staging and treatment approach for a pediatric patient with confirmed Wilms tumor?

Wilms Tumor Staging and Treatment Approach

Wilms tumor staging follows the Children's Oncology Group (COG) system, which stratifies patients by anatomic extent of disease and histology to guide risk-adapted therapy combining surgery, chemotherapy, and selective radiation therapy. 1, 2

Staging System

The COG staging system classifies Wilms tumor based on surgical and pathologic findings:

• Stage I: Tumor confined to kidney, completely resected with intact capsule, no vascular invasion beyond renal capsule 1, 2

• Stage II: Tumor extends beyond kidney but completely resected; includes penetration through renal capsule, invasion of renal sinus vessels, or tumor biopsy prior to removal 1, 2

• Stage III: Residual nonhematogenous tumor confined to abdomen; includes positive surgical margins, peritoneal contamination, lymph node involvement, or tumor rupture before/during surgery 1, 2

• Stage IV: Hematogenous metastases (lung, liver, bone, brain) or lymph node metastases outside abdomen 1, 2

• Stage V: Bilateral renal involvement at diagnosis 1, 2

Histologic Classification

Histology is the critical prognostic determinant that fundamentally alters treatment intensity:

• Favorable histology (FH): Standard triphasic pattern without anaplasia; represents approximately 90% of cases with 4-year overall survival exceeding 98% for stage I-II disease 3

• Anaplastic histology (AH): Presence of enlarged, hyperchromatic nuclei with abnormal mitotic figures; subdivided into focal versus diffuse anaplasia 3

• Diffuse anaplasia: Carries significantly worse prognosis with 4-year event-free survival of 82.6% for stage II, 64.7% for stage III, and only 33.3% for stage IV disease 3

Treatment Algorithm by Stage and Histology

Stage I-II Favorable Histology

• No radiation therapy required 4, 1
• Postoperative chemotherapy with vincristine and dactinomycin (45 mcg/kg IV every 3-6 weeks for up to 26 weeks per FDA labeling) 5, 4
• 4-year overall survival: 98.3% for stage I, 92% for stage II 3

Stage III Favorable Histology

• Postoperative abdominal radiation therapy to tumor bed 4, 1
• Triple-agent chemotherapy: vincristine, dactinomycin, and doxorubicin using either conventional or pulsed dosing schedules 4
• Critical to avoid local recurrence given residual disease risk 3

Stage IV Favorable Histology

• Aggressive triple-agent chemotherapy (vincristine, dactinomycin, doxorubicin) 4
• Radiation therapy to metastatic sites as indicated, particularly lung metastases 4, 1
• Caveat: Pulmonary nodules <5 mm at diagnosis remain controversial regarding clinical significance and treatment implications 2

Stage I Anaplastic Histology

• Vincristine and dactinomycin for 18 weeks 3
• Important: 4-year overall survival of 82.6% is significantly worse than stage I favorable histology (98.3%), despite lower stage 3

Stage II-IV Diffuse Anaplastic Histology

• Intensive four-drug regimen: vincristine, doxorubicin, cyclophosphamide, and etoposide for 24 weeks 3
• Mandatory flank/abdominal radiation therapy 3
• Critical pitfall: Stage II diffuse anaplasia had no local recurrences with this approach, validating the aggressive combined modality strategy 3

Stage V (Bilateral Disease)

• Requires specialized approach with nephron-sparing surgery when feasible 1
• 4-year event-free survival of 43.8% and overall survival of 55.2% for bilateral anaplastic histology 3
• Universal genetic testing mandatory for all bilateral cases including methylation/copy-number analysis of chromosome 11p15.5, WT1 sequencing, and testing for REST, TRIM28, DIS3L2, and CTR9 6

Genetic Testing and Surveillance Implications

Genetic Testing Recommendations

All patients with Wilms tumor should undergo panel testing for predisposition genes, particularly:

• REST, CTR9, TRIM28, DIS3L2: Found in 2-7% of nonfamilial cases 6
• TRIM28 variants: Present in 86% of epithelial-predominant tumors; these patients have better prognosis and may be candidates for reduced-intensity therapy 6
• Bilateral disease: Requires comprehensive testing including 11p15.5 methylation analysis and WT1 sequencing regardless of syndromic features 6

Post-Treatment Surveillance

• All bilateral tumor survivors: Abdominal ultrasound every 3 months until at least 8 years of age, regardless of genetic findings, due to field defect risk for second tumors 6
• Identified pathogenic variants (REST, CTR9, TRIM28, DIS3L2): Renal ultrasound every 3 months until 8 years of age for carriers 6
• Female patients with bilateral disease: Higher risk for subsequent tumors than males; requires particularly vigilant surveillance 6

Critical Management Principles

All patients must be managed by multidisciplinary teams with pediatric oncology expertise to maximize the current >90% overall survival rate while minimizing long-term treatment toxicities. 1, 7

The dramatic improvement from <20% survival historically to current rates exceeding 80-90% represents careful risk stratification balancing cure against treatment-related morbidity. 4, 1, 7