Lymphovascular space invasion is an independent risk factor for nodal disease and poor outcomes in endometrioid endometrial cancer

Abstract

Objective

Adjuvant radiotherapy improves local control but not survival in women with endometrial cancer. This benefit was shown in staged patients with “high intermediate risk” (HIR) disease. Other studies have challenged the need for systematic staging including lymphadenectomy. We sought to determine whether LVSI alone or in combination with other histologic factors predicts lymph node (LN) metastasis in patients with endometrioid endometrial cancer.

Methods

A retrospective review was conducted of patients with endometrioid endometrial carcinoma who had confirmed presence/absence of LVSI and clinicopathologic data necessary to identify HIR criteria. Kaplan–Meier curves were generated and univariate and multivariate analyses performed as appropriate.

Results

We identified 757 eligible patients and 628 underwent systematic lymphadenectomy for staging purposes. In the surgically staged group, 242 (38%) patients met uterine HIR criteria and 196 (31%) had LVSI. Both HIR and LVSI were significantly associated with LN metastasis. Among the HIR positive group, 59 had LN metastasis (OR 4.46, 95% CI 2.72–7.32, P < 0.0001). Sixty-six LVSI positive patients had nodal metastasis (OR 11.04, 95% CI 6.39–19.07, P < 0.0001). The NPV of LVSI and HIR negative specimens was 95.6% and 93.4% respectively. In multivariate analysis, PFS and OS were significantly reduced in both LVSI positive (P < 0.0001) and HIR patients (P < 0.0001) when compared to patients who were LVSI and HIR negative.

Conclusions

HIR status and LVSI are highly associated with LN metastasis. These features are useful in assessing risk of metastatic disease and may serve as a surrogate for prediction of extrauterine disease.

Introduction

Endometrial cancer is the most common gynecologic malignancy in the United States with 43,000 new cases and 7900 deaths in 2010 alone [1]. Eighty percent of women present at an early stage and thus overall 5-year survival rates approach 90–97% [2], [3]. Systematic surgical staging including lymph node (LN) evaluation remains an important prognostic tool in women with endometrial cancer. Recently however, two large European studies have called into question the therapeutic value of routine lymph node sampling in patients afflicted with this disease. These studies evaluated 1914 patients and found that survival was not different between patients who received lymphadenectomy and those who only underwent a total abdominal hysterectomy and removal of adnexae alone [4], [5]. There is however, extensive controversy surrounding these results with regards to study design and inclusion criteria.

In the near future, uterine histopathologic features may become increasingly important and used as a surrogate risk marker and determinant of adjuvant therapy for patients with high risk disease. Several trials including PORTEC-1 and GOG protocol 99 have established factors such as age, grade, and depth of myometrial invasion as characteristics associated with increased risk for recurrence [2], [6]. Interestingly, these studies did not examine the association of these markers with lymph node metastasis, a significant predictor of outcome. LVSI in particular has been previously shown in a few, small scale studies to be a biomarker for both nodal disease and recurrence but the use of this finding remains controversial [7], [8]. We hypothesized that LVSI may independently serve as a predictor of nodal disease in patients with endometrioid endometrial cancer in comparison to patients who meet other high risk criteria. The secondary aims of this study are the impact that LVSI has on overall and progression free survival in a cohort of nearly 800 patients.