# Renal sarcomas in children and adolescents: a retrospective, multicenter cohort study

## TL;DR

This study examines the characteristics and outcomes of rare kidney cancers in children and adolescents, highlighting the need for tailored treatment strategies.

## Contribution

The study provides a comprehensive analysis of patient and disease characteristics across a large pediatric renal sarcoma cohort.

## Key findings

- Clear cell sarcoma of the kidney and Ewing sarcoma were the most common types, with significant differences in age at diagnosis.
- Overall survival varied significantly by sarcoma type, with metastases strongly associated with worse outcomes.
- Molecular alterations were most frequently observed in clear cell sarcoma of the kidney and Ewing sarcoma.

## Abstract

Renal sarcomas arise rarely in children and adolescents and represent a histologically and biologically diverse disease category. Consequently, standardizing optimal therapies for pediatric renal sarcomas remains challenging. Leveraging a large North American research collaborative, the purposes of this study were to evaluate the current state of patient, disease, and survival characteristics among pediatric renal sarcomas and to expose knowledge gaps that will inform future discovery.

Patients 21 years or younger and treated for a primary renal sarcoma between January 1st, 2000 and November 30th, 2022 were identified through the Pediatric Surgical Oncology Research Collaborative. Patient (e.g., demographics) and disease (e.g., histology, stage, molecular alterations) characteristics were abstracted from contributing institutions. Descriptive statistics, Pearson-Chi square (categorical variables), Kruskal–Wallis (continuous variables), Cox regression (Hazard ratios), and Kaplan–Meier 4-year event-free and overall survival (OS) analyses were completed.

Among 158 patients, clear cell sarcoma of the kidney (CCSK; n = 94), Ewing sarcoma (EWS; n = 33), and undifferentiated sarcoma (n = 8) predominated. Sarcoma type correlated significantly with age at diagnosis (p < 0.0001), with infantile fibrosarcoma (IFS) and CCSK occurring in the youngest patients, whereas EWS and synovial sarcoma presented in the oldest. Predisposition syndromes were identified in 11/155 (7.1%) patients, most commonly DICER1 and Li-Fraumeni. Multimodal therapies varied significantly across sarcoma types (p = 0.0008), although nephrectomy was uniform. Tumor thrombectomy was performed in 9 patients (6 with EWS). When tested, somatic molecular alterations were observed principally in CCSK (17/38; 45%) and EWS (26/26; 100%; p = 0.001). At 4 years, OS differed significantly by sarcoma type, ranging from highest to lowest as follows: CCSK 0.927 (95% CI 0.845–0.967), EWS 0.901 (95% CI 0.723–0.967), undifferentiated sarcoma 0.833 (95% CI 0.273–0.975), IFS 0.667 (95% CI 0.054–0.945), and rhabdomyosarcoma 0.500 (95% CI 0.111–0.804; p = 0.036). Hematogenous metastases occurred most in the lungs (n = 19 total; 10 with EWS), followed by bone (n = 12), which occurred only with CCSK (n = 9) and EWS (n = 3). Two patients developed brain metastases (one each with CCSK and rhabdomyosarcoma). At 4 years, OS was 0.957 (95% CI 0.888–0.984) for patients presenting without metastases and 0.717 (95% CI 0.545–0.833) for those with metastases (p = 0.00015).

Renal sarcomas presenting in children and adolescents comprise a heterogeneous disease category with unique patient, clinical, and molecular characteristics that complicate standardizing therapeutic strategies beyond CCSK and EWS.

None.