Analysis of Genitourinary Rhabdomyosarcoma in Phase 3 Clinical Trials

Abstract Purpose: Pediatric Rhabdomyosarcoma (RMS) is a morbid and often lethal condition characterized by a paucity of clinical data. Beyond a detailed risk categorization system, it is unclear if genitourinary (GU) sites (bladder/prostate, paratesticular, female organs) have outcomes distinct from non-GU sites. This study pools primary data from phase-3 clinical trials involving pediatric RMS to evaluate this question. Methods and Materials: We obtained primary data from three Children’s Oncology Group pediatric RMS trials (NCT00075582, NCT00354744, NCT00354835) evaluating low- (LR), intermediate- (IMR), and high risk (HR) Pediatric RMS. Survival analysis was conducted using the Kaplan-Meier method, with Event-Free Survival (EFS) defined per protocol specifications. Results: 599 subject records were included in the analysis (111 GU RMS, 488 non-GU RMS). For subjects with GU RMS, overall survival (OS) was superior to non-GU RMS (HRR 0.55, 95% CI 0.35-0.87, p=0.009). In this same group EFS superiority was not statistically significant compared to non-GU RMS (HRR 0.88 95% CI, 0.63-1.22, p=0.43). In the LR population, GU primary site was associated with improved OS that was not statistically significant (HRR 0.37 95% CI 0.07-1.84, p=0.21) and less favorable EFS (HRR 2.84 95% CI, 1.13-7.12, p=0.02). Conclusions: In RMS, a GU primary site is linked to improved OS compared to non-GU sites, although LR GU RMS shows less favorable EFS. Our findings reinforce the association between GU primary sites and better OS outcomes in RMS, warranting further investigation into the surrogacy of EFS for OS in GU RMS.