Introduction/Background Lymphovascular space invasion (LVSI) is a recognized predictor of nodal spread and survival in endometrioid endometrial adenocarcinoma (EEC). However, the impact of LVSI extent on local versus distant recurrence has not been established.

Methodology We conducted a multicenter retrospective cohort study of patients with FIGO 2009 stage I node-negative EEC surgically staged between 01/01/2012 and 12/31/2019 at two tertiary cancer centers. Staging included total hysterectomy and lymph node assessment. LVSI extent was categorized according to WHO/FIGO 2023 criteria as focal (F-LVSI; <5 vascular spaces involved) or substantial (S-LVSI; ≥5 vascular spaces involved). Recurrence and death were considered events. Competing-risk analysis was performed and controlled for multicenter clustering.

Results Over a median follow-up of 61 months (range, 0.8–164), 1555 patients met inclusion criteria, of whom 65 (4.2%) had S-LVSI, 119 (7.7%) F-LVSI, and 1371 (88%) no LVSI. Overall, there were 172 events: 56 local recurrences, 43 distant recurrences, and 73 deaths without recurrence. Stage IB disease was noted in 35 patients (54%) with S-LVSI, 44 (37%) with F-LVSI, and 115 (8.4%) with no LVSI (P<0.001). Overall, 345 patients (22%) received adjuvant treatment—55% in the S-LVSI, 67% in the F-LVSI, and 15% in the no-LVSI groups (P<0.001). Of these patients, 304 (88%) received brachytherapy alone and 40 (12%) chemotherapy alone. On multivariate analysis, compared to no LVSI, S-LVSI was associated with increased risk of distant recurrence (aHR 2.29; 95% CI: 1.17–4.46) but not local recurrence. Compared to F-LVSI, S-LVSI was not associated with increased risk of local recurrence (aHR 0.59; 95% CI: 0.36–0.96). Age at surgery, histological grade, and depth of myoinvasion were independently associated with local or distant recurrence (figure 1).

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Abstract 587 Figure 1

a-Graph showing cumulative incidence of local recurrence based on extent of LVSI. b-Graph showing cumulative incidence of distant recurrence based on extent of LVSI. c-Multivariate competing risk analysis for progression comparing local versus distant recurrence (N=1550)

Conclusion S-LVSI, compared to no LVSI, was associated with increased risk of distant recurrence. S-LVI was not associated with increased risk of local recurrence compared to F-LVSI.

Disclosures Vicky Makker reports providing unpaid consultion for: ArQule, AstraZeneca, Clovis Oncology, Cullinan, Duality, Eisai, Faeth Therapeutics, GlaxoSmithKline, Jazz, Immunocore, ITeos Therapeutics, Kartos Therapeutics, Karyopharm Therapeutics, Lilly, Merck, Moreo, Morphosys, Prelude, Novartis, Takeda, Zymeworks. Research Funding for: AstraZeneca (Inst), Bayer (Inst), Bristol-Myers Squibb (Inst), Clovis Oncology (Inst), Duality (Inst), Eisai (Inst), Faeth Therapeutics (Inst), Karyopharm Therapeutics (Inst), Lilly (Inst), Merck (Inst), Takeda (Inst), Zymeworks (Inst), Cullinan (Inst). Receiving travel, and accommodation expenses from Eisai, and Merck. Other Relationship with: IBM. She is supported in part by the NIH/NCI Cancer Center Support Grant P30 CA008748.

Mario M. Laitao Jr. is an ad hoc speaker for Intuitive Surgical, Inc., has consulted for Medtronic, and has served on the advisory boards of Ethicon/Johnson & Johnson and Immunogen.

Ane Gerda Eriksson reports receiving funds from Intuitive Surgical, Inc. and AstraZeneca.

Nadeem R. Abu-Rustum reports grant funding from GRAIL paid to the institution.