Extent of macroscopic vascular invasion predicts distant metastasis in primary leiomyosarcoma of the inferior vena cava

Background In retroperitoneal leiomyosarcoma (RP LMS), the predominant issue is distant metastasis (DM). We sought to determine variables associated with this outcome and disease‐specific death (DSD). Methods Data were retrospectively collected on patients with primary RP LMS treated at a high‐volume center from 2002 to 2023. For inferior vena cava (IVC)‐origin tumors, the extent of macroscopic vascular invasion was re‐assessed on each resection specimen and correlated with preoperative cross‐sectional imaging. Crude cumulative incidences were estimated for DM and DSD and univariable and multivariable models were performed. Results Among 157 study patients, median tumor size was 11.0 cm and 96.2% of cases were intermediate or high grade. All patients underwent complete resection, 56.7% received chemotherapy (43.9% neoadjuvant) and 14.6% received radiation therapy. Only tumor size and grade and not site of tumor origin (e.g., IVC vs. other) were associated with DM and DSD ( p < 0.05). Among 64 patients with IVC‐origin tumors, a novel 3‐tier classification was devised based on the level of intimal disruption, which was associated with both DM ( p = 0.007) and DSD (0.002). Conclusion In primary RP LMS, only tumor size and grade are predictive of DM and DSD. In IVC‐origin tumors, the extent of macroscopic vascular invasion is also strongly predictive of these outcomes.