What is the prognostic importance of lymphovascular space invasion in the absence of lymph node metastasis for early-stage endometrial cancer?

To the Editor,

We read with great interest the recently published article “Substantial lymph-vascular space invasion (LVSI) as a predictor of distant relapse and poor prognosis in low-risk early-stage endometrial cancer” from Tortorella et al. [1]. The authors aimed to assess the prognostic impact of a three-tiered scoring system of LVSI in patients with endometrioid histology, well-moderately differentiated (G1–G2), superficially infiltrating (<50% myometrial invasion) endometrial cancer. They excluded patients with type II, poorly differentiated, myometrial invasion >50% or International Federation of Obstetrics and Gynecology (FIGO) stage higher than IA endometrial cancer. In this way, they intended to address the pure effect of LVSI on prognosis in patients with no other risk factors.

In the current study, 43.5% (228/524) of the whole study population, 38.8% (22/57) of the LVSI positive group did not undergo lymph node evaluation. However, the presence of LVSI in women without lymph node evaluation constitutes a substantial risk for occult lymph node metastasis. In a National Cancer Database Analysis, Jorge et al. [2] included 25,907 patients with endometrioid adenocarcinomas who underwent surgical staging, including lymph node assessment. The authors aimed to define the risk of lymph node metastasis associated with LVSI stratified by grade and stage. The study revealed that the presence of LVSI increased the risk of nodal metastases from 0.7% to 11.4% for women with T1A grade 1 tumor and from 1.3% to 13.2% for women with T1A grade 2 tumor [2]. In this context, it is clear that there may be patients with occult lymph node metastases in the LVSI positive group without lymph node evaluation in the Tortorella study.

Surgical treatment of patients predicted to have early-stage endometrial adenocarcinoma is total hysterectomy, bilateral salpingo-oophorectomy, and staging [3]. The lymph node metastasis is addressed as stage IIIC according to the FIGO 2009 staging system and associated with adverse survival outcomes in endometrial adenocarcinoma patients [4, 5]. Therefore, possible occult lymph node metastasis possesses an important confounding effect when evaluating the prognostic value of the LVSI in the present study.

We thank authors for this significant study. However, we suggest the authors to estimate the prognostic value of focal and substantial LVSI in a subgroup analysis, including only women who underwent lymph node evaluation.