Risk-Adjusted Real-World Survival Outcomes Across SIOP-RTSG And NWTSG/COG Protocol–Care Ecosystems In Children With Wilms Tumor: A Two-Country, Multicenter Cohort Study
Background: The SIOP-RTSG and NWTSG/COG approaches differ primarily in the timing of nephrectomy and the clinical information used for risk stratification. Direct comparisons are complicated because protocol selection is closely linked to treatment center, institutional practice, and healthcare-system context. We compared real-world survival outcomes between two protocol–care ecosystems after adjustment for harmonizable baseline risk factors. Methods: This retrospective, two-country, multicenter cohort study included 183 consecutive children treated for Wilms tumor between 1997 and 2025 at centers in Azerbaijan and Türkiye. Of these, 78 received SIOP-RTSG-based treatment and 105 received NWTSG/COG-based treatment. Overall survival (OS) and event-free survival (EFS) were estimated using the Kaplan–Meier method and compared using the log-rank test. Cox proportional hazards models were used to evaluate the association of protocol–care ecosystem with OS and EFS after adjustment for age category and harmonized disease stage. Preoperative response and histological risk were evaluated exploratively within the SIOP-RTSG cohort. Results: Five-year OS was 84.8% in the SIOP-RTSG group and 87.0% in the NWTSG/COG group, with no difference between the survival curves (log-rank p=0.978). Five-year EFS was 76.3% and 80.7%, respectively (log-rank p=0.661). In the multivariable OS model, the protocol–care ecosystem was not independently associated with mortality (adjusted hazard ratio [aHR] 1.046, 95% confidence interval [CI] 0.453–2.413; p=0.916). Older age category (aHR 2.858, 95% CI 1.513–5.400; p=0.0012) and stage III–V disease (aHR 3.364, 95% CI 1.117–10.132; p=0.031) were independently associated with poorer OS. Similarly, the protocol–care ecosystem was not associated with EFS (aHR 0.963, 95% CI 0.501–1.853; p=0.911), whereas older age category (aHR 1.869, 95% CI 1.173–2.978; p=0.0085) and stage III–V disease (aHR 2.556, 95% CI 1.186–5.510; p=0.0166) were associated with a higher event risk. Within the SIOP-RTSG cohort, poor preoperative response was associated with inferior OS (HR 5.957, 95% CI 1.542–23.016; p=0.0097) and EFS (HR 3.640, 95% CI 1.341–9.883; p=0.0112). High-risk histology was associated with inferior EFS (HR 3.748, 95% CI 1.010–13.903; p=0.0482), but not significantly with OS.Conclusions: After adjustment for age and stage, the protocol–care ecosystem was not independently associated with OS or EFS. Older age and advanced-stage disease were the principal unfavorable prognostic factors, while poor preoperative response and high-risk histology provided additional prognostic information within the SIOP-RTSG cohort. These findings do not establish equivalence between the SIOP-RTSG and NWTSG/COG strategies but indicate that both may achieve satisfactory survival outcomes when implemented within structured multidisciplinary care systems. Due to the retrospective, observational nature of the study and the use of anonymized patient data, the requirement for written informed consent was waived by the institutional review boards.