Impact of time to relapse (TTR) and metastasectomy (MTS) on survival in leiomyosarcoma (LMS): A CanSaRCC study.

Abstract

11567 Background: Approximately 40% of LMS patients (pts) experience relapse despite standard care of surgical resection ± radiotherapy. Upon relapse, pts with advanced disease receive palliative systemic therapy. Often reserved for pts with oligometastatic disease, the role of MTS remains unclear due to a lack of randomized trials. Longer time from curative surgery to relapse (TTR) is associated with better outcomes in LMS pts who undergo MTS but its prognostic value has not been established in those treated without MTS. This study evaluates the effect of TTR on outcomes in LMS pts with metachronous metastases treated with systemic therapy ± surgery. Methods: This real-world study included advanced LMS pts treated at 4 Canadian sarcoma centers (2010–2022) who underwent curative resection, subsequent relapse, and systemic treatment ± MTS. Data were retrieved from the ethics-approved Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) database. Primary and secondary endpoints were overall survival (OS) stratified by TTR (< 6 vs ≥6 months from the completion of curative resection); and MTS, respectively. Exploratory analysis evaluated the impact of MTS in pts with low disease burden at relapse ( < 2 sites). Kaplan-Meier survival analysis and log-rank tests were used to compare OS, and Cox proportional hazards models identified independent predictors, with p < 0.05 considered significant. Results: A total of 113 pts (median age 56y) were included. Median follow-up was 38.4 months (mo). Majority (n = 93, 82%) were female and 38 (34%) had uterine leiomyosarcoma (uLMS). Relapse occurred in 109 pts (96%) with 73/109 pts (70%) having < 2 metastatic sites at relapse. TTR was < 6 months (TTR < 6) in 31/109 pts (28%) and 43/109 pts (39%) underwent MTS. Pts with TTR ≥6 months (TTR≥6) had significantly longer median OS (mOS) than those with TTR < 6 (32.9 vs 15.6mo, p = 0.006). Metastasectomy was associated with a significantly longer mOS in the whole cohort (50.4 vs 17.6mo, p < 0.0001) as well as the subgroup of patients with < 2 metastatic sites at relapse (50.6 vs 15.6mo, p < 0.0001). The mOS was 50.4 vs 24.7mo in pts with TTR≥6 who underwent MTS and those who did not, respectively (p < 0.0001). Among pts with TTR < 6 who had MTS, median OS was 44.8mo compared with 9.4mo in pts without surgery (p = 0.005). No other variables (e.g., tumor grade, primary site, metastatic burden, gender, or age) impacted OS. Both MTS (HR 0.26, 95% CI 0.16-0.49, p = 0.000) and TTR ≥ 6 (HR 0.55, 95% CI 0.33-0.91, p = 0.02) remained independent predictors of favorable OS in multivariate analysis. Conclusions: TTR≥6 was associated with longer OS in LMS pts. OS improved significantly with MTS, particularly in pts with longer TTR, though those with TTR < 6 also benefited to a lesser extent. These results underscore the role of MTS as part of an individualized treatment strategy to optimize outcomes in advanced LMS.