Insights into rhabdomyosarcoma in the adolescent and young adult population: a comprehensive clinical study from the French Society of Pediatric Oncology (SFCE) Malignant Mesenchymal Tumor (MMT) Committee and the French Sarcoma Group (GSF-GETO)

BACKGROUND: Rhabdomyosarcoma (RMS) in adolescent and young adults (AYAs) has a poor prognosis. This study aims to evaluate the prognostic significance of patient, disease, and treatment characteristics, including factors known to impact survival in patients with pediatric RMS, in the AYA population. PATIENTS AND METHODS: We conducted a retrospective review of patients aged 15-25 years treated for RMS in France between 2006 and 2014. Patients were either enrolled in the RMS-2005 study (NCT00379457) or identified through the French databases RRePS, NetSarc, and Conticabase. RESULTS: A total of 115 patients were included: 64 (56%) aged 15-18 years and 51 (44%) aged 19-25 years. Most patients were male (70%), had a fusion-positive alveolar subtype (51%), lymph node involvement (53%), and metastatic disease (44%). The 5-year overall survival and event-free survival for the entire cohort were 46% [95% confidence interval (CI) 36-55] and 41% (95% CI 32-50), respectively. Multivariate analysis confirmed the prognostic significance of Intergroup Rhabdomyosarcoma Study groups III and IV, analyzed as distinct groups and compared with pooled groups I-II [hazard ratio (HR) 2.21, 95% CI 0.78-6.27 for group III; HR 5.62, 95% CI 2.06-15.33 for group IV; P < 0.001], alveolar subtype (HR 2.50, 95% CI 1.42-4.40, P = 0.002), and the 19-25 years age group (HR 1.85, 95% CI 1.10-3.12, P = 0.02). The care setting (pediatric, AYA, or adult unit) did not significantly impact outcome (P = 0.84). Seventy-seven percent of patients with localized disease had a chemotherapy score of 1 (defined as ≥8 cycles of chemotherapy including an alkylating agent with doxorubicin or d-actinomycin or vincristine), which was associated with improved prognosis (HR 0.25, 95% CI 0.09-0.74, P = 0.012, stratified on propensity score). CONCLUSIONS: Despite multimodal treatment, RMS in AYAs has a poorer prognosis than in children, partly due to the higher frequency of unfavorable risk factors. Their inclusion in the ongoing FaR-RMS study (NCT04625907) should lead to a homogenization of their therapeutic management and, ultimately, improve their prognosis.