<h3>Study Objective</h3> To compare oncological outcomes of women with stage II -IIIc endometrial cancer (EC) who underwent minimally invasive surgery (MIS) versus laparotomy. <h3>Design</h3> A retrospective cohort study. <h3>Setting</h3> Academic multi-center. <h3>Patients or Participants</h3> Consecutive women with EC treated at 11 Israeli institutions between 2002 and 2017 were recorded in an assimilated database with a median follow-up of 52 months (range 12-120 months). Women with stage II -IIIc were stratified into groups by intentional route of surgery; MIS vs. laparotomy. Clinical, pathological and outcome data were compared. <h3>Interventions</h3> MIS and laparotomy. <h3>Measurements and Main Results</h3> Three hundred and four women met criteria: 200 underwent laparotomy and 104 MIS. Women in the MIS group were younger, had lower rate of diabetes and lower CA-125 level. Women who underwent laparotomy had higher grade EC and more advanced stage disease; Odds Ratio (OR) and 95% Confidence Interval (CI) 0.34 (0.21-0.56) and 0.56 (0.34-0.92), respectively. Brachytherapy rate was comparable between groups (p=0.715). In a multivariable analysis, including age, comorbidities, disease stage, tumor grade and lymph-vascular space invasion, MIS was not associated with an increased risk for recurrence, progression or decreased overall survival. However, patients operated by MIS had higher risk to recur locally (vaginal cuff or pelvic) (26.9% vs. 16.5%, p=0.032, OR, 1.86, 95% CI 1.05-3.30). MIS was the only independent factor associated with local recurrence, adjusted OR, 2.09, 95% CI 1.12-3.90. <h3>Conclusion</h3> In women with stage II-IIIc EC, MIS was associated with an increased risk for local recurrence compared to laparotomy.
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