Treatment of Isolated Lung Relapse in Wilms Tumor
For pediatric patients with isolated lung relapse of Wilms tumor, aggressive multimodal therapy combining salvage chemotherapy with surgical metastasectomy (when feasible) and consideration of lung radiation therapy offers the best chance for cure, with long-term survival rates approaching 40-60% in appropriately selected patients. 1, 2
Risk Stratification at Relapse
The prognosis and treatment approach depend critically on several factors that must be assessed immediately:
Primary tumor histology is the most important prognostic factor: patients with favorable histology at initial diagnosis have significantly better outcomes (5-year OS 89.2%) compared to high-risk histology (5-year OS 44.4%), with diffuse anaplasia having the worst prognosis (OS 22.2%) 2
Initial treatment intensity determines salvage options: patients who received less intensive primary therapy (no doxorubicin or radiation) have more therapeutic options available at relapse 1
Time to relapse influences prognosis: later relapses generally respond better to retreatment than early relapses 1
Response to salvage chemotherapy is a critical prognostic marker, with non-responding disease associated with significantly worse outcomes 2
Salvage Chemotherapy Regimen
The specific chemotherapy approach should be tailored based on prior treatment:
For patients who did not receive doxorubicin initially: incorporate anthracyclines into the salvage regimen as these patients retain sensitivity to this drug class 1
For patients previously treated with vincristine/dactinomycin/doxorubicin: consider cyclophosphamide/etoposide-based regimens (Regimen M), which have demonstrated efficacy in the metastatic setting 3
High-dose chemotherapy with stem cell rescue should be considered for high-risk relapses, though the optimal role continues to be investigated 1
Ifosfamide versus cyclophosphamide: the comparative benefit and toxicity profile between these agents in the relapse setting remains under investigation, though both are active against Wilms tumor 1
Role of Surgical Metastasectomy
Complete surgical resection of lung metastases is a critical component of curative therapy:
Pulmonary metastasectomy is indicated when complete remission can be achieved, as this allows avoidance of lung irradiation and its associated late effects 2
Complete resection of all visible metastases is essential, as persistence of metastases after local treatment is associated with significantly worse outcomes 2
Repeated thoracotomies are often indicated to achieve complete clearance of all pulmonary disease 4
Timing of surgery: metastasectomy should be performed after initial response to salvage chemotherapy has been assessed, typically after 2-3 cycles 2
Radiation Therapy Considerations
Lung radiation therapy plays an important role in selected patients:
Lung RT should be administered to patients with incomplete response to chemotherapy or those with viable tumor in resected metastases 2, 3
Patients who achieve complete radiographic response may avoid lung RT if all disease is surgically resected, though this must be balanced against relapse risk 3
For patients who received lung RT during primary treatment: re-irradiation requires careful consideration of cumulative doses and late effects, particularly cardiac toxicity given prior anthracycline exposure 4
Response Assessment and Monitoring
Rigorous imaging surveillance is essential during salvage therapy:
Chest CT with thin cuts (approximately 1 cm slice thickness) is required to accurately evaluate pulmonary metastases and response to therapy 5
Response evaluation should occur after every 2 cycles of chemotherapy to avoid delaying surgery in non-responding disease 5
Radiographic complete response does not equal pathologic complete response: 25-40% of patients with apparent complete radiographic response harbor viable tumor, underscoring the need for surgical resection even with excellent imaging response 5
Critical Pitfalls to Avoid
Do not delay surgical intervention in patients with resectable disease showing good response to chemotherapy, as complete resection is essential for cure 2
Do not rely solely on imaging to determine treatment completion; histologic confirmation of response through surgical resection is critical 5
Do not use standard chest imaging protocols: ensure thin-cut chest CT is performed, as small pulmonary nodules may be missed with thicker slices 5
Do not underestimate the importance of tumor biology: patients with anaplastic histology, rhabdoid tumor of the kidney (RTK), or clear cell sarcoma of the kidney (CCSK) require more aggressive approaches and have poorer outcomes 1
Special Considerations for Genetic Predisposition
For patients with identified genetic predisposition syndromes (WT1, Beckwith-Wiedemann, DICER1, TRIM28):
Continue surveillance of the contralateral kidney with renal ultrasound every 3 months, as these patients remain at risk for second primary tumors 4, 6, 5
Genetic counseling and cascade testing of family members should be pursued if not already completed 4
Surveillance should continue until at least age 8 years for most predisposition syndromes 4, 6
Expected Outcomes
With appropriate multimodal therapy:
Overall 5-year survival for isolated lung relapse ranges from 40-60% in more recently treated patients, representing substantial improvement from historical 30% survival rates 7, 1
Patients with favorable histology and complete response to salvage therapy have the best outcomes, with some series reporting survival exceeding 70% 2
Patients with high-risk features (anaplastic histology, incomplete response, early relapse) have significantly worse prognosis and may benefit from investigational approaches 1, 2