What is the stage and recommended treatment for an 8-month-old female with favorable/non-anaplastic histology Wilms tumor, who underwent neoadjuvant chemotherapy and nephrectomy of the right kidney, with residual tumor suspected at the margin of resection and viable tumor thrombus present at the resection margins of the renal vessels?

Stage III Wilms Tumor with Positive Vascular Margins: Treatment Intensification Required

This patient has Stage III Wilms tumor by both COG and SIOP criteria due to positive vascular margins at the renal vein resection site, requiring intensified adjuvant chemotherapy with dactinomycin and vincristine plus radiation therapy to the tumor bed. 1

Staging Confirmation

The pathology report clearly establishes Stage III disease based on two independent staging systems:

• Children's Oncology Group (COG): Stage III due to residual tumor suspected with viable tumor present at margin of resection 2
• International Society of Pediatric Oncology (SIOP): Stage III due to viable tumor thrombus present at resection margins of the renal vessels 2

The positive vascular margin on the renal vein is the critical factor that upstages this tumor from Stage II to Stage III, despite negative lymph nodes and no capsular penetration. 2

Risk Stratification

This tumor demonstrates intermediate-risk histology with the following characteristics:

• Favorable/non-anaplastic histology (most important prognostic factor) 3
• Post-therapy classification showing >33% viable tumor remaining after neoadjuvant chemotherapy 2
• Blastemal histology present in <66% of viable tumor 2

The intermediate-risk classification indicates partial response to neoadjuvant therapy but not complete response, necessitating treatment intensification. 2

Recommended Treatment Protocol

Adjuvant Chemotherapy

Dactinomycin plus vincristine combination chemotherapy is required for Stage III favorable histology Wilms tumor. 1

• Dactinomycin dosing: 45 mcg/kg intravenously once every 3 to 6 weeks as part of multi-agent combination chemotherapy for up to 26 weeks 1
• This represents intensification beyond Stage I-II protocols due to the positive surgical margins 1
• The combination regimen should be administered according to COG protocols for Stage III disease 3

Radiation Therapy

Flank radiation therapy to the tumor bed is mandatory for Stage III disease with positive margins. 2

• Radiation is indicated specifically because of the residual disease at the vascular margin 2
• The radiation field should encompass the entire tumor bed and the area of positive margin 3
• Timing should be coordinated with chemotherapy cycles to optimize efficacy while minimizing toxicity 3

Critical Management Considerations

Genetic Testing

Comprehensive genetic testing should be performed immediately given the young age (8 months) and to guide surveillance:

• Test for REST, CTR9, TRIM28, and DIS3L2 pathogenic variants (found in 2-7% of nonfamilial cases) 2
• WT1 sequencing and 11p15.5 methylation analysis should be considered 2
• TRIM28 testing is particularly relevant given the intermediate-risk histology; 86% of epithelial-predominant tumors harbor TRIM28 variants, and these patients may be candidates for reduced-intensity therapy in future protocols 2

Long-Term Surveillance Protocol

Intensive surveillance is required due to the positive margins and young age:

• Abdominal ultrasound every 3 months until at least 8 years of age, regardless of genetic findings, due to field defect risk for second tumors 2
• If pathogenic variants are identified (REST, CTR9, TRIM28, DIS3L2), continue renal ultrasound every 3 months until 8 years of age 2, 4
• Female patients have higher risk for subsequent tumors than males and require particularly vigilant surveillance 2

Monitoring During Treatment

• Serial imaging to assess response to adjuvant therapy 3
• Careful monitoring for chemotherapy-related toxicity, particularly hematologic toxicity with dactinomycin 1, 5
• Renal function monitoring given single kidney status 6

Common Pitfalls to Avoid

Do not treat this as Stage II disease despite the favorable histology and negative lymph nodes—the positive vascular margin definitively establishes Stage III classification and requires both chemotherapy intensification and radiation therapy. 2, 1

Do not delay radiation therapy—it should be initiated promptly after surgical recovery and coordinated with chemotherapy cycles. 3

Do not omit genetic testing in this very young patient, as identification of predisposition syndromes will fundamentally alter surveillance strategies and inform family counseling. 2, 4

Do not use single-agent chemotherapy—Stage III disease requires combination chemotherapy with both dactinomycin and vincristine. 1

Prognosis

With appropriate multimodal therapy including combination chemotherapy and radiation, survival rates for Stage III favorable histology Wilms tumor exceed 90%. 3 The favorable histology is the most important positive prognostic factor, while the positive margins and intermediate-risk post-therapy classification necessitate aggressive treatment but do not preclude excellent outcomes. 3