Residual absolute volume of blastema as a predictor of clinical outcomes in patients with Wilms tumor

Blastemal-type Wilms tumor (WT) after preoperative chemotherapy is considered high risk (HRWT). The multinational SIOP WT 2001 study investigated whether residual absolute volume of blastema (AVB) functions as an independent prognostic factor across WT subtypes. AVB was calculated from preoperative tumor volume, necrosis percentage, and viable blastema using prospectively collected data from 3,549 patients with unilateral WT treated 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%). Multivariable Cox regression adjusted for age, sex, and local stage confirmed significantly worse event-free survival (EFS) and overall survival (OS) for patients exceeding AVB thresholds: IRWT (≥ 20 mL): EFS HR 2.93 (95% CI 2.08-4.12) and OS 2.76 (1.32-5.77); HRWT (≥ 100 mL) EFS 2.89 (1.59-5.26) and OS 3.25 (1.45-7.27); stage IV (≥ 10 mL) EFS 5.78 (3.65-9.17) and OS 4.59 (2.57-8.17). Patients above these thresholds had significantly lower 2-year EFS (p<0.0001). Among stage II-III IRWT patients with AVB ≥ 20 mL, those treated with doxorubicin had superior 2-year EFS versus those not treated with doxorubicin (87% versus 69.2%; p=0.0064). The authors conclude that AVB after preoperative chemotherapy is a strong, independent predictor of both EFS and OS in WT across risk groups.