(P 329) DISTANT METASTASIS IN RETROPERITONEAL LEIOMYOSARCOMA: TUMOR SIZE, GRADE AND MORE?

Objective: Distant metastasis is the predominant issue in patients with retroperitoneal leiomyosarcoma (RP LMS) after complete resection. This is the rationale for including this histologic type in the ongoing STRASS2 phase 3 study, which randomizes retroperitoneal sarcoma patients to neoadjuvant chemotherapy followed by surgery versus surgery alone. We sought to determine variables associated with distant metastasis (DM) and disease-specific death (DSD) in RP LMS to apply clinical practice as well as STRASS2 trial analysis and future translational investigation.

Methods: Data were collected on patients with primary RP LMS who underwent surgery at the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, a high-volume specialist center, from 2002-2023. Patients who had incomplete resection, recurrence or metastatic disease at presentation and gynecologic- or genitourinary-origin tumors were excluded. Descriptive data were summarized and crude cumulative incidence curves were estimated for DM and DSD in a competing risk setting. Univariable and multivariable Fine and Gray models were performed to assess the association of specific variables of interest (e.g., tumor size) on outcome.

Results: Our study included 157 patients with a 2:1 female to male ratio. Median tumor size was 11.0 cm and 96.2% of patients had an intermediate or high grade (FNCLCC 2 or 3) tumor. The tumor origin as determined at surgery and by pathologic examination of the resection specimen was inferior vena cava in 40.8% of patients, another major vessel (e.g., renal, iliac) in 18.5%, gonadal vein in 14.6% and unclear in 26.1%. All patients underwent complete resection. Blood transfusions were given at surgery in 46.5% of patients and the overall frequency of major complications was low (14.0%). Chemotherapy was given in 56.7% (43.9% neoadjuvant) and radiation therapy in 14.6% of patients. With a median follow-up of 3.8 years, the overall 5-year incidence of local recurrence was extremely low (2.4%) but was as high as 60.1% for DM. On univariable and multivariable models, only tumor size and grade were significantly associated with DM and DSD (all p < 0.05). No other variable, including site of tumor origin or chemotherapy given was found to have any association with these outcomes. Female gender was found to demonstrate a trend for lower incidences of DM (p = 0.09) and DSD (p = 0.08) on multivariable analysis. Five-year incidences of DM and DSD by tumor size and grade are shown in the Table. Post-hoc analysis of preselected patients with 1) DM less than 1 year from surgery or 2) no evidence of disease > 5 years confirmed that tumor size and grade are the only variables that significantly differ in these subgroups.

Conclusion: Among conventional clinicopathologic data, tumor size and grade are the only predictors of DM and DSD in patients with RP LMS. As data from the prospective STRASS2 trial emerge, these two variables can help to identify subgroups that are most impacted by neoadjuvant chemotherapy. Our study also highlights the critical unmet need for better biomarkers (e.g., in the tumor microenvironment or circulating blood) to stratify DM risk in RP LMS.