Abstract
OBJECTIVES: Retroperitoneal sarcoma (RPS) is highly heterogeneous, leading to different risks of distant metastasis (DM) among patients with the same clinical stage. This study aims to develop a quantitative method for assessing intratumoral heterogeneity (ITH) using preoperative contrast-enhanced CT (CECT) scans and evaluate its ability to predict DM risk. METHODS: We conducted a retrospective analysis of 274 PRS patients who underwent complete surgical resection and were monitored for ≥ 36 months at two centers. Conventional radiomics (C-radiomics), ITH radiomics, and deep-learning (DL) features were extracted from the preoperative CECT scans and developed single-modality models. Clinical indicators and high-throughput CECT features were integrated to develop a combined model for predicting DM. The performance of the models was evaluated by measuring the receiver operating characteristic curve and Harrell's concordance index (C-index). Distant metastasis-free survival (DMFS) was also predicted to further assess survival benefits. RESULTS: The ITH model demonstrated satisfactory predictive capability for DM in internal and external validation cohorts (AUC: 0.735, 0.765; C-index: 0.691, 0.729). The combined model that combined clinicoradiological variables, ITH-score, and DL-score achieved the best predictive performance in internal and external validation cohorts (AUC: 0.864, 0.801; C-index: 0.770, 0.752), successfully stratified patients into high- and low-risk groups for DM (p < 0.05). CONCLUSIONS: The combined model demonstrated promising potential for accurately predicting the DM risk and stratifying the DMFS risk in RPS patients undergoing complete surgical resection, providing a valuable tool for guiding treatment decisions and follow-up strategies. CRITICAL RELEVANCE STATEMENT: The intratumoral heterogeneity analysis facilitates the identification of high-risk retroperitoneal sarcoma patients prone to distant metastasis and poor prognoses, enabling the selection of candidates for more aggressive surgical and post-surgical interventions. KEY POINTS: Preoperative identification of retroperitoneal sarcoma (RPS) with a high potential for distant metastasis (DM) is crucial for targeted interventional strategies. Quantitative assessment of intratumoral heterogeneity achieved reasonable performance for predicting DM. The integrated model combining clinicoradiological variables, ITH radiomics, and deep-learning features effectively predicted distant metastasis-free survival.