The Prognostic Impact of Substantial Lymphovascular Space Invasion in Women with FIGO Stage I Uterine Endometrioid Carcinoma with Pathologically Negative Nodal Evaluation

Abstract

Substantiallymphovascular space invasion (LVSI) is an important predictor of lymph node involvement in women with endometrial carcinoma. However, its prognostic significance in women with stage I who had pathologic negative nodal evaluation (PNNE) was not fully evaluated. We aimed to evaluate the prognostic significance of substantial LVSI on recurrence-free (RFS), disease-specific (DSS) and overall survival (OS) in women with FIGO stage I uterine endometrioid adenocarcinoma (EC). Our uterine cancer database was queried for women with stage I EC who had a hysterectomy and PNNE at our institution between 1/1990 and 11/2022. Postoperatively, patients were managed with observation or adjuvant radiation therapy (RT) with pelvic external beam RT or vaginal cuff brachytherapy (VB). Women with synchronous malignancies and those who received adjuvant chemotherapy were excluded. Pathologic specimens were retrieved and LVSI was quantified by Gynecology pathologists (none, focal or substantial). Patients' demographics, surgical and pathologic variables were analyzed. Predictors of RFS, DSS and OS using univariate (UVA) and multivariate analysis (MVA) were studied. One thousand fifty-two patients were identified with a median age of 63 years and median follow-up of 9.7 years. Median number of examined lymph node (LN) were 9 (range 4-18). 907 patients (86.2%) had no LVSI, 87 (8.3%) had focal and 58 (5.5%) had substantial LVSI. In patients with focal LVSI, 32.2% received pelvic RT and 39.1% received VB. In patients with substantial LVSI, 20.7% received pelvic RT and 58.6% received VB.Recurrence was diagnosed in 86 patients (8.2%). While any LVSI was associated with tumor recurrence, there was no significant difference for the site of initial recurrence between patients with focal vs. substantial LVSI. 5-year RFS was 93.3% (95% CI 91.5-95.1), 76.8% (67.2-87.7) and 79.1% (67.6-95.3) for no, focal and substantial LVSI. The 5-year DSS was 97.6% (96.5-98.7), 83.5% (75-93.1), and 90% (81.8-99.9); and 5-year OS was 90.7% (88.7-92.8), 72.8% (62.9-84.2) and 86% (76.2-97.2), respectively. Independent predictors of worse 5-year RFS and DSS include any LVSI, age > 60 years, higher tumor grade. Independent predictors of worse 5- year OS include any LVSI, age > 60, high comorbidity burden, and higher tumor grade. Our large data suggest similar recurrence-free, disease specific and OS for women with stage I uterine endometrioid carcinoma who had pathologically negative nodal evaluation and substantial or focal LVSI. There was no significant difference for the site of initial recurrence between patients with focal or substantial LVSI. Multi-institutional pooled analyses may be needed to validate our results.