BACKGROUND: The role of preoperative inflammatory markers in predicting postoperative outcomes has been investigated in different types of cancer. However, little is known about retroperitoneal sarcoma (RPS). This study aimed to evaluate the association between preoperative inflammatory status and major postoperative morbidity in patients undergoing RPS surgery. METHODS: Data on patients undergoing surgery for primary RPS between 2008 and 2022 at three specialist sarcoma centers were analyzed. The preoperative inflammatory status was evaluated, assessing the C-reactive protein (CRP) value, the neutrophil/lymphocyte ratio (NLR), and the platelet/lymphocyte ratio (PLR). The primary outcome was 90-day major postoperative morbidity. The best-balanced cutoff values to apply in the uni- and multivariable analysis were calculated using a receiver operating characteristic (ROC) curve analysis. RESULTS: Data were available for 239 patients. Major postoperative complications occurred in 52 of 235 patients (22.1%). Increased median values of CRP, NLR, and PLR were significantly higher in patients with dedifferentiated liposarcoma (DDLPS) (p <
0.002). As such, further analysis focused only on this specific histotype. On multivariable analysis, after adjusting for potential confounders, the association between increasing CRP and NLR with 90-day major postoperative morbidity remained significant, with an OR of 2.96 (95% CI: 1.03-8.49, p = 0.044) for CRP >
61 mg/L, and with an OR of 4.69 (1.55-14.20, p = 0.006) for NLR >
4.85. CONCLUSION: Elevated preoperative levels of CRP and NLR are independently associated with major postoperative morbidity in patients affected by primary retroperitoneal DDLPS. These findings may help decision-making and optimize perioperative management in these patients.