Sex Differences in Complications and Outcomes of Wilms Tumor: Is There a Role for Sex-based Approaches in Nephroblastoma Management?

Abstract

Background: Sex-specific differences in complications and outcomes among patients with Wilms tumor (WT) during treatment and follow-up remain poorly understood. This study aimed to investigate these differences, hypothesizing that outcomes may be improved through sex-based management considerations.

Methods: We conducted a retrospective, single-center comparative study of patients treated between 2009 and 2024 at a pediatric tertiary care center.

Results: One hundred thirty-four patients with WT were included. No significant sex differences were observed in age, weight, height, or presenting symptoms. Bilateral WT was significantly more frequent in females (13 [18%] vs. 2 [3%], P = 0.011), whereas left-sided WT in males (35 [57%] vs. 28 [38%], P = 0.037). At diagnosis, no sex-related differences were noted in imaging findings (metastases, renal or caval vein thrombus, tumor size) or laboratory values. A caval thrombus was identified in 9 patients (7%), with no initial sex difference. After neoadjuvant therapy, persistent thrombus was significantly more common in females (6 [8%] vs. 0 [0%], P = 0.007). No sex differences were found in intraoperative renal vein thrombosis, but intraoperative caval thrombosis occurred significantly more often in females (6 [8%] vs. 0 [0%], P = 0.007). Tumor rupture/spillage, nodal sampling, and nodal involvement were comparable between groups. Histologic subtype and risk distribution were comparable between sexes, whereas local stage differed significantly, with stage III disease more frequent in females (45% vs. 17%, P = 0.001) and stage II disease more frequent in males (34% vs. 12%, P = 0.004). Follow-up included 131 patients (3 lost). Median age at last follow-up was 9.2 years (range: 2.3 to 25.7). Event-free survival (EFS) was significantly higher in males than in females (56 boys [94%] vs. 57 girls [80%], P = 0.040). Females experienced significantly more events (14 [20%] vs. 4 [6%], P = 0.040), although no differences were observed in event type, relapse site, overall survival (OS), or mortality.

Conclusions: Female patients with WT may experience a more complex clinical course, reflected by higher rates of bilateral disease, persistent and intraoperative caval thrombus, inferior EFS, and a greater frequency of events during follow-up.