Substantial Lymphovascular Space Invasion Is an Adverse Prognostic Factor in High-Risk Endometrial Cancer

Abstract

Approximately 15% of patients with endometrial cancer present with high-risk disease (HREC). Moreover, assessing the extent of lymphovascular space invasion (LVSI) may provide prognostic insight among patients with HREC. The aim of this study was to determine whether the extent of LVSI can serve as a prognostic factor in HREC. All cases of ESMO-ESGO-ESTRO 2016 classified HREC in the Danish Gynecological Cancer Database (DGCD) diagnosed from 2005 to 2012 were reviewed for the presence and extent of LVSI (categorized using a 3-tiered definition). We used the Kaplan-Meier analysis to calculate actuarial survival rates, both adjusted and unadjusted Cox regression analyses were used to calculate the proportional hazard ratio (HR). A total of 376 patients were included in our analysis. Among 305 patients with stage I/II HREC, 8.2% and 6.2% had focal or substantial LVSI, respectively, compared with 12.7% and 38.0% of 71 patients with stage III/IV HREC, respectively. Moreover, the estimated 5-yr recurrence-free survival rate was significantly lower among patients with substantial LVSI compared with patients with no LVSI for both stage I/II (HR: 2.8; P=0.011) and stage III/IV (HR: 2.9; P=0.003) patients. Similarly, overall survival was significantly lower among patients with substantial LVSI for both stage I/II (HR: 3.1; P<0.001) and stage III/IV (HR: 3.2; P=0.020) patients. In patients with HREC, substantial LVSI is an independent adverse prognostic factor for lymph node and distant metastases, leading to reduced survival. Thus, the extent of LVSI should be incorporated into routine pathology reports in order to guide the appropriate choice of adjuvant treatment.

Prognostic relevance of the molecular classification in high-grade endometrial cancer for patients staged by lymphadenectomy and without adjuvant treatment

“…LVSI is a known risk factor for lymph node metastasis, recurrence and shorter survival in EC [8,[36][37][38][39]. Studies have now reported on the clinical relevance of assessing the extent of LVSI, independent of other clinicopathological features [16,39,40]. The prognostic role of substantial LVSI has previously been explored in the context of the molecular subgroups in intermediate (−high) risk EC patients [3,40], where substantial LVSI was an independent prognostic factor.…”

“…There were 713 patients with high-grade EC registered in the DGDC, of which 460 had haematoxylin and eosin-stained slides available for pathology review regarding assessment and quantification of LVSI, by four pathologists, as described in detail by Peters et al [16](Supplementary methods), and selection of tumour tissue for molecular profiling. Formalin-fixed paraffin-embedded tumour tissue was collected from 426 EC.…”

FIGO staging of endometrial cancer: 2023

“…An extensive body of literature supports these findings. Randomized trials, prospective cohort studies, large database series, and single-institution reports consistently demonstrate that LVSI is an independent and strong prognostic factor for the recurrence of endometrial carcinoma [ 66 67 68 69 ]. A retrospective registry study of more than 1,500 patients from Sweden with Stage I–III identified LVSI as the strongest independent risk factor for lymph node metastases and decreased survival, even in the absence of lymph node metastases in patients with endometrioid adenocarcinomas [ 67 ].…”

Endometrial cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

“…In contrast to substantial LVSI, minimal or focal LVSI has limited impact on prognosis. [12][13][14] Alongside these characteristics, L1 cell adhesion molecule (L1CAM) is another significant indicator of high-risk disease. 15,16 Expression of L1CAM is most frequent in p53-abnormal (p53-abn) tumours but is also predictive of worse outcome among tumours with no specific molecular profile (NSMP).…”