Effect of substantial lymphovascular space invasion on location of first disease recurrence in surgical stage I endometrioid endometrial adenocarcinoma.

Objective: Lymphovascular invasion can predict nodal spread and recurrence in endometrioid endometrial cancer; however, the impact of lymphovascular invasion quantification on local versus distant recurrence in surgically staged patients has not yet been established.

Methods: This multicenter, retrospective cohort study included surgically staged patients with International Federation of Obstetrics and Gynecology 2009 stage I node-negative endometrioid endometrial cancer. Patients were treated between January 2012 and December 2019 at 2 tertiary cancer centers. Staging included a total hysterectomy and lymph node assessment. The extent of lymphovascular invasion was defined using the World Health Organization criteria as focal (<5 vessels involved on at least 1 pathology slide) or substantial (≥5 vessels involved). Recurrence and death were considered as events. A competing risk analysis was performed and controlled for multicenter clustering.

Results: Overall, 1555 patients met the inclusion criteria: 65 (4.2%) had substantial invasion, 119 (7.7%) had focal, and 1371 (88.2%) had no invasion. The median follow-up was 61.5 months (range; 0.8-133.9). There were 173 evaluable events among the 1554 patients: 56 local recurrences, 43 distant recurrences, and 74 deaths without recurrence. Deep (>50%) myoinvasion and grade 3 histology were more frequently observed in patients with substantial myoinvasion. Overall, 323 patients (20.8%) received adjuvant therapy. The 5-year cumulative incidence failure rates for any recurrence were 6.0% for no, 19.5% for focal, and 19.0% for substantial invasion. Compared to no lymphovascular invasion, substantial invasion was associated with an increased risk of distant recurrence (adjusted HR 2.29, 95% CI 1.17 to 4.46).

Conclusions: In patients with surgical stage I endometrioid endometrial cancer, the focal and substantial lymphovascular invasion was associated with a 3-fold increased risk of cumulative incidence failure versus no lymphovascular invasion. Patients with substantial invasion had more deeply invasive and grade 3 tumors and appeared to experience more distant than local recurrences. These findings challenge the International Federation of Obstetrics and Gynecology 2023 staging classification that combines no lymphovascular invasion and focal lymphovascular invasion into a single risk category.