Prognostic biomarkers in retroperitoneal dedifferentiated liposarcoma and their clinical impact on patient management.

11546 Background: The prognosis of patients (pts) with retroperitoneal dedifferentiated liposarcoma (DDLPS) is mainly driven by tumor size, grade, patient age, and completeness of resection. Furthermore, the expression of myogenic markers has been associated with poorer outcomes. Prognostic nomograms, such as Sarculator, and transcriptomic signatures—most notably the Complexity INdex in SARComas (CINSARC)—have improved risk stratification. However, given the rarity of DDLPS and the limited evidence guiding treatment, identifying robust prognostic biomarkers remains a major challenge. This study evaluated the prognostic impact of clinical, morphological, and molecular features and assessed the performance of Sarculator and CINSARC in retroperitoneal DDLPS. Methods: A retrospective observational study was conducted on pts with retroperitoneal DDLPS treated at the Veneto Institute of Oncology (IOV)-IRCCS between 2004 and 2024. Tumor samples with adequate material underwent morphological, immunohistochemical, and molecular analyses, including CINSARC assessment. Disease-free survival (DFS) and overall survival (OS) were evaluated in surgically treated pts (Cohort 1), while progression-free survival (PFS) and OS were assessed in pts receiving first-line chemotherapy (Cohort 2). Sarculator was applied to Cohort 1, and its discriminative ability was evaluated using ROC curves. Concordance between CINSARC and Sarculator was also examined. Results: A total of 119 pts were included. In the overall population, tumor grade (3 vs 2: HR, 2.23; 95% CI 1.06 - 4.70; p = 0.03) and age (<65 vs ≥65: HR, 0.43; 95% CI 0.22 - 0.85; p = 0.02) were the most significant predictors of OS. In Cohort 1, these variables remained determinants of survival. In Cohort 2, sex, tumor size and differentiation significantly affected survival, with rhabdomyoblastic differentiation conferring the worst prognosis (p = 0.04). When Sarculator was applied to Cohort 1, a moderate discriminative ability was observed for OS (AUC = 0.75), with a lower performance for DFS (AUC = 0.64). Molecular analyses were performed on 32 samples; MYOG transcripts, indicative of rhabdomyoblastic differentiation, were detected in 8 cases. Based on CINSARC, 11 pts (34.4%) were low risk and 21 (65.6%) high risk. Agreement between Sarculator and CINSARC was moderate for both OS (Cohen’s Kappa, κ = 0.40) and DFS (κ = 0.55). Conclusions: To our knowledge, our study is among the largest conducted in retroperitoneal DDLPS specifically evaluating clinico-pathological features and the performance of Sarculator and CINSARC. Our findings support the negative prognostic impact of rhabdomyoblastic differentiation. Further investigation of differentiation patterns, combined with prognostic nomograms and transcriptomic signatures, may improve the identification of high-risk pts and support more personalized therapeutic strategies.