Residual Absolute Volume of Blastema as a Predictor of Clinical Outcomes in Patients With Wilms Tumor: A Report From the SIOP WT 2001 Study

PURPOSE The International Society of Paediatric Oncology–Renal Tumour Study Group (SIOP-RTSG) classifies blastemal-type Wilms tumor (WT) after preoperative chemotherapy as high-risk (HRWT). It remains unresolved whether residual absolute volume of blastema (AVB) functions as an independent prognostic factor across WT subtypes. MATERIALS AND METHODS AVB was calculated from preoperative tumor volume, necrosis percentage, and viable blastema using prospectively collected data from 3,459 patients with unilateral WT treated in the SIOP WT 2001 study between 2001 and 2018. Martingale residual plots defined AVB thresholds discriminating survival in localized HRWT, intermediate-/low-risk WT (IRWT/LRWT), and metastatic WT (stage IV). Complete AVB data were available for 1,802 patients (51.2%); 298 (16.5%) had stage IV disease. Of 1,504 patients with localized WT, 265 (17.6%) had HRWT, 1,203 (79.9%) had IRWT, and 36 (2.4%) had LRWT. RESULTS Multivariable Cox regression adjusted for age, sex, and local stage confirmed significantly worse survival for patients exceeding these AVB thresholds: (1) IRWT (≥20 mL): Hazard ratio for event-free survival (EFS) 2.93 (95% CI, 2.08 to 4.12) and overall survival (OS) 2.76 (95% CI, 1.32 to 5.77); (2) HRWT (≥100 mL): EFS 2.89 (95% CI, 1.59 to 5.26) and OS 3.25 (95% CI, 1.45 to 7.27); and (3) stage IV (≥10 mL): EFS 5.78 (95% CI, 3.65 to 9.17) and OS 4.59 (95% CI, 2.57 to 8.17). Patients above these thresholds had significantly lower 2-year EFS ( P < .0001). In stage II to III IRWT patients with AVB ≥20 mL, those treated with doxorubicin had superior EFS versus those without (87.6%, 95% CI, 81.5 to 94.1 v 69.2%, 95% CI, 59.8 to 80.1; P = .0064). CONCLUSION AVB after preoperative chemotherapy is a strong, independent predictor of both EFS and OS in WT across risk groups. An AVB of ≥20 mL identifies a clinically relevant subset of patients with IRWT who may benefit from intensified therapy with doxorubicin. These findings support the use of AVB as a stratification criterion in future SIOP-RTSG protocols.