The Prognostic Role of Lymphovascular Space Invasion in Endometrioid Endometrial Cancer

A newly published retrospective cohort study underscores the significant prognostic role of lymphovascular space invasion (LVSI) in patients with early-stage, node-negative endometrioid endometrial cancer. Drawing from over three decades of clinical data, the study reinforces the integration of LVSI into modern risk stratification systems and adjuvant treatment decisions for FIGO stage I disease.

Conducted at a tertiary academic center in Turkey, the study analyzed outcomes in 469 patients with FIGO 2009 stage I endometrioid endometrial carcinoma who underwent full surgical staging, including lymphadenectomy. All patients had confirmed negative lymph node status, eliminating confounding from occult nodal metastases. LVSI was present in 17.7% of the cohort and was independently associated with significantly worse disease-free survival (DFS) and overall survival (OS).

At five years, patients with LVSI had a DFS rate of 86.4% compared to 96.3% in those without, and an OS rate of 72.1% versus 91.2%. On multivariate analysis, LVSI remained a robust predictor of poor prognosis, with hazard ratios of 4.80 for recurrence and 3.33 for overall mortality—even after adjusting for tumor grade, depth of myometrial invasion, and adjuvant therapy.

These findings are consistent with prior multicenter investigations, including the LySEC study, which similarly demonstrated that LVSI significantly increases recurrence risk and diminishes survival, even in the absence of nodal disease. Notably, the current study reinforces these conclusions with a particularly homogeneous population and long-term follow-up data.

Beyond its statistical significance, LVSI was found to cluster with other high-risk features. Patients with positive LVSI were more likely to present with larger tumors, grade 3 histology, deep myometrial invasion, and stage IB disease. Importantly, they were also more likely to experience distant rather than locoregional recurrence—a pattern that may suggest hematogenous dissemination and points to the biological aggressiveness associated with LVSI.

Despite the use of adjuvant therapies—primarily external beam radiotherapy and, in some cases, chemotherapy—patients with LVSI still fared worse. Multivariate models showed that receipt of adjuvant therapy itself was associated with poorer survival outcomes, a finding the authors attribute to treatment indication bias. In real-world clinical settings, patients with more aggressive disease are naturally selected for additional treatment, potentially masking therapeutic benefit.

The study also provides relevant context for current staging and treatment guidelines. The 2023 FIGO revision incorporated LVSI extent—specifically, involvement of five or more vessels—as a staging criterion, following evidence from the PORTEC trials that highlighted its link with pelvic recurrence and distant metastasis. However, in this study, LVSI was evaluated in binary terms (present vs. absent), due to limitations in archival pathology data. Still, the results support the predictive value of even focal LVSI and justify its inclusion in risk models when quantification is not feasible.

In clinical practice, these findings reinforce the need for pathologic assessment of LVSI during initial diagnosis and for its consideration in decisions about postoperative management. For patients in the high–intermediate-risk group—which includes all LVSI-positive individuals in this study—tailored adjuvant strategies may be necessary to reduce distant recurrence and improve long-term outcomes.

The authors also highlight a growing intersection between oncologic risk and reproductive planning. For women of reproductive age diagnosed with early-stage disease, fertility-preserving strategies, such as oocyte cryopreservation, must be weighed against the risk of recurrence associated with features like LVSI. Recent literature suggests that long-term monitoring of children born via fertility-preserving approaches is critical, particularly regarding cardiovascular and neurodevelopmental outcomes.

While the study is limited by its retrospective design, absence of molecular profiling, and lack of SLN mapping in earlier years, its findings are highly relevant to global clinical practice—especially in resource-limited settings where access to molecular testing remains variable. The authors call for future prospective studies integrating molecular and histopathologic data to refine risk stratification even further.

As staging and treatment protocols continue to evolve, this study makes a compelling case for anchoring lymphovascular space invasion as a cornerstone variable in early-stage endometrial cancer management.