What is the SIOP (Societe Internationale d'Oncologie Pediatrique) regimen for Wilms tumor?

SIOP Regimen for Wilms Tumor

The SIOP (International Society of Paediatric Oncology) approach to Wilms tumor involves preoperative chemotherapy followed by surgery and risk-adapted postoperative treatment, in contrast to the North American upfront surgery approach. 1

Core Treatment Strategy

The SIOP protocol follows a sequential treatment paradigm that fundamentally differs from the Children's Oncology Group (COG) approach:

Preoperative Chemotherapy Phase

• All patients receive preoperative chemotherapy before surgical resection, which aims to reduce tumor volume and facilitate safer surgical resection 1, 2
• This initial chemotherapy is administered regardless of clinical stage at presentation 1
• The preoperative approach results in different histological assessment patterns compared to upfront surgery, as tumor response to chemotherapy becomes a prognostic factor 1

Surgical Phase

• Surgery is performed after completion of preoperative chemotherapy, with the goal of complete tumor resection 1
• Laparoscopic nephrectomy may be considered for selected cases meeting SIOP criteria, though these criteria can be expanded at experienced centers after multidisciplinary discussion 3
• Surgical timing is critical, and the procedure should be performed once adequate tumor response is achieved 2

Postoperative Treatment Stratification

Treatment intensity after surgery depends primarily on histological classification and stage, with recent protocols incorporating additional prognostic factors 1:

For Blastemal-Type Wilms Tumor (High-Risk Histology)

• Intensified postoperative chemotherapy is administered for blastemal-type tumors, which represent approximately 8.6% of unilateral non-metastatic cases 4
• The SIOP WT 2001 protocol demonstrated improved 5-year event-free survival of 80% compared to 67% in the previous SIOP 93-01 protocol through treatment intensification 4
• Stage I blastemal-type tumors showed the most significant benefit, with event-free survival improving from 71% to 96% with the addition of doxorubicin 4
• Age at diagnosis, tumor stage, and tumor volume at surgery are independent prognostic factors requiring consideration 4

Radiotherapy Considerations

• Local radiotherapy is administered when indicated based on stage and histology, though timely implementation within recommended timeframes can be challenging in real-world settings 2
• Radiotherapy should ideally be initiated promptly after surgery, though median delays of 21 days have been reported in practice 2

Outcomes and Comparative Effectiveness

• The SIOP strategy achieves 5-year overall survival of approximately 92%, comparable to North American approaches despite different treatment sequences 2
• Both SIOP and COG approaches achieve excellent outcomes exceeding 90% survival for all stages combined, demonstrating that either strategy is effective when properly implemented 1
• The preoperative chemotherapy approach results in higher-stage tumors at diagnosis being downstaged, with greater volume decrease observed compared to other Wilms tumor subtypes 4

Critical Implementation Considerations

Common pitfalls to avoid:

• Do not delay surgery indefinitely waiting for complete tumor response - proceed with resection once adequate response is achieved, as prolonged chemotherapy without surgery does not improve outcomes 2
• Ensure multidisciplinary team coordination for treatment decisions, particularly regarding surgical timing and approach 3
• Monitor for treatment compliance closely - the SIOP approach requires strict adherence to chemotherapy protocols before surgery 2
• Plan radiotherapy logistics in advance to minimize delays in administration, as timely delivery impacts local control 2

Historical Context and Evolution

• Early SIOP trials in the 1960s-1970s demonstrated progressive improvement in recurrence-free survival from 22% without chemotherapy to 56.6% with SIOP trial chemotherapy 5
• The protocol has evolved to incorporate more sophisticated risk stratification based on histology, molecular markers, and treatment response 1
• Recent protocols (SIOP WT 2001 and beyond) have intensified treatment for high-risk histologies while maintaining excellent outcomes 4