(P 376) IMPACT OF SITE OF ORIGIN ON THE PROGNOSIS OF PATIENTS WITH PRIMARY RESECTABLE NON-UTERINE ABDOMINAL LEIOMYOSARCOMA

Objective: Leiomyosarcoma (LMS) accounts for 20% of primary non-uterine abdominal (retroperitoneal/intraperitoneal/pelvic) sarcomas. Prognosis following resection is driven by the propensity for distant recurrence. Current efforts are focused on understanding the biologic factors, and underlying molecular determinants, that promote metastatic progression, and how to mitigate these. Further refinement of prognostic algorithms requires high-quality prospectively collected data with complete long-term follow-up. Here we aimed to determine the impact of site of origin of abdominal LMS on oncologic outcomes.

Methods: Sequential patients who underwent resection of primary non-metastatic abdominal LMS between January 1997 and December 2022 at two high-volume referral centres were included. We excluded patients with recurrent sarcoma, synchronous distant metastases at presentation, radiation-associated LMS, and LMS of uterine, cutaneous, subcutaneous, or abdominal wall origin. We included LMS arising from the following sites of origin: i) Vascular (named vein - IVC, renal, ovarian, iliac, SMV & etc.); ii) Visceral (stomach, intestinal, adrenal, ureter, prostate); iii) Indeterminate (site could not be discerned on review of preoperative imaging and examination of resected specimen). LMS of vascular origin were further sub-classified as within the sex-hormone drainage pathway (SHDP) or not (non-SHDP). SHDP was defined as originating from ovarian/testicular, medial left renal, or adrenal veins, or mid-IVC (i.e. primary and secondary veins draining the sex-hormone producing organs), as assessed by expert body imaging specialists/sarcoma pathologists. Disease-specific survival (DSS) following resection (t=0) was calculated using the Kaplan-Meier method and curves compared using the log rank test. Crude cumulative incidence (CCI) of subsequent local recurrence (LR) and distant metastasis (DM) were calculated within a competing risks framework.

Results: A total of 305 patients with abdominal LMS (203 female, 102 male, median age 60 yrs) met inclusion criteria and comprise the study cohort. For the entire cohort, DSS at 5 years following resection was 73% (95% CI 67-79), with a median follow-up time of 40 mos (IQR 21-86). Site of origin was Vascular in 216, Visceral in 49, and Indeterminate in 40 patients. The three site groups were comparable with respect to patient age, sex and resection status, while Visceral LMS were more commonly Grade 1, and Indeterminate LMS were larger (Table 1). DSS at 5yrs was 73% for the Vascular, 84% for the Visceral, and 60% for the Indeterminate groups (p=0.1, Fig.1A). CCI of DM was higher in LMS of Indeterminate origin (72% at 5yrs), than for Vascular (58%) and Visceral origin (41%) (p=0.025, Fig.1B). CCI of LR was low, and did not differ between site groups (at 5 yrs: 2.4% for Vascular, 4.2% for Visceral, 2.6% for Indeterminate). Upon univariate analysis, DSS was found to depend on grade and size, while CCI-DM depended on grade, size and site of origin (Table 2).

Of the 216 patients with LMS of Vascular origin, 133 were within the SHDP, while 83 were not. These two subgroups were comparable with respect to patient age, resection status, tumour grade and size, but sex was more commonly female in the SHDP than non-SHDP subgroup (80% vs. 52%, p=0.0001). There was a trend towards higher DSS and lower DM in the SHDP than the non-SDHP subgroup (Fig.2A, B); this trend was more pronounced in male patients, where 5-yr DSS was 82% vs. 66%, and CCI-DM 49% vs. 63%, in SHDP vs. non-SHDP cases, respectively (Fig.2C, D).


Conclusion: Patients with LMS arising from a Visceral site had a relatively good prognosis. A site of origin that could not be determined was associated with a very high probability of distant metastasis, and compromised survival. Site of origin of abdominal LMS, in particular as it relates to the sex-hormone drainage pathway, may contribute to prognosis through as yet undefined molecular drivers.