OBJECTIVE: To report the learning curve and outcomes after our first 105 patients underwent robotic hysterectomy and pelvic–aortic lymphadenectomy for the comprehensive staging of endometrial cancer. METHODS: We prospectively collected patient demographics, operative times, complications, pathologic results, and length of stay on all patients who underwent robotic hysterectomy pelvic–aortic lymphadenectomy for clinical stage I or occult stage II endometrial carcinoma. RESULTS: One hundred five patients at The Ohio State University between March 2006 and April 2008 underwent exploration with the intent of robotic hysterectomy pelvic–aortic lymphadenectomy. Ninety-two (87.6%) were completed robotically and 13 (12.4%) were converted. The probability of conversion was 15% (95% confidence interval [CI] 8.4–25.7), 24% (95% CI 12.4–39.9), 35% (95% CI 15.9–59.6), and 48% (95% CI 19.1–77.8) for a body mass index of 40, 45, 50, and 55 kg/m², respectively. The median body mass index was 34 kg/m² (range 19–58). In patients who underwent a robotic hysterectomy pelvic–aortic lymphadenectomy (n=79, 75%) or a robotic hysterectomy–pelvic lymphadenectomy (n=6, 5.7%), the average operating time from skin opening to closure was 242 minutes (±50 minutes). The median estimated blood loss was 99 mL (±83 mL). The median number of lymph nodes recovered was 29 (range 9–56), 21 (range 5–40) pelvic nodes and 9 (range 2–21) aortic nodes. The median length of stay was 1 night. After analysis of the data, we determined approximately 20 cases are needed to gain proficiency. CONCLUSION: Early experience demonstrates that robotic hysterectomy pelvic–aortic lymphadenectomy for endometrial cancer is feasible, with approximately 20 procedures needed to gain proficiency. LEVEL OF EVIDENCE: III

OBJECTIVE: To evaluate the effect of tumor capsule rupture on disease prognosis in stage I epithelial ovarian cancer. METHODS: All patients with International Federation of Gynecology and Obstetrics stage I epithelial ovarian cancer operated on at the Mayo Clinic and The Ohio State University between January 1991 and December 2007 were identified. Relevant tumor characteristics, procedures performed, adjuvant therapies, and follow-up were recorded and analyzed. Inclusion criteria included comprehensive staging. Cox proportional hazards, Kaplan-Meier estimation, log rank test, and χ² test were used for statistical analyses. RESULTS: There were 161 cases that met inclusion criteria. Seventy-four (46%) patients had intact capsules without positive cytology or surface involvement; 61 (38%) had capsule rupture; 33 (20%) had positive cytology; and 22 (14%) had surface involvement. Overall, 22 of 161 (14%) patients recurred and 12 of 161 (7%) patients died of their disease. In univariable analysis, both intraoperative capsule rupture and positive cytologic washings portended worse disease-free survival (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.5–8.9; P=.004 and HR 5.2, 95% CI 2.1–12.3; P<.001, respectively) and disease-specific survival (HR 4.1, 95% CI 1.3–15.4; P=.018 and HR 5.9, 95% CI 1.8–19.3; P=.005, respectively). In multivariable analysis, capsule rupture (HR 4.2, 95% CI 1.8–10.9; P=.001) and positive cytologic washings (HR 6.4, 95% CI 2.5–16.0; P<.001) remained independent predictors of worse disease-free survival. Disease-free survival and disease-specific survival were shortest for stage IC cases with positive cytology, surface involvement, or both, that also had intraoperative rupture. CONCLUSION: In stage I epithelial ovarian cancer, intraoperative capsule rupture portends a higher risk of disease recurrence and death from disease. Careful intraoperative removal of ovarian masses is important, and recognizing the higher-risk nature of such cases is imperative. LEVEL OF EVIDENCE: III

PURPOSE: Selinexor inhibits exportin-1 (XPO1) resulting in nuclear accumulation of tumor suppressor proteins including p53 and has clinical activity in endometrial cancer (EC). The primary end point was to assess progression-free survival (PFS) with once-weekly oral selinexor in patients with advanced or recurrent EC. PATIENTS AND METHODS: ENGOT-EN5/GOG-3055/SIENDO was a randomized, prospective, multicenter, double-blind, placebo-controlled, phase III study at 107 sites in 10 countries. Patients 18 years or older with histologically confirmed EC were enrolled. All had completed a single line of at least 12 weeks of taxane-platinum combination chemotherapy and achieved partial or complete response. Patients were assigned to receive 80 mg oral selinexor once weekly or placebo with 2:1 random assignment (ClinicalTrials.gov identifier: NCT03555422 ). RESULTS: Between January 2018 and December 2021, 263 patients were randomly assigned, with 174 allocated to selinexor and 89 to placebo. The median PFS was 5.7 months (95% CI, 3.81 to 9.20) with selinexor versus 3.8 months (95% CI, 3.68 to 7.39) with placebo (hazard ratio [HR], 0.76 [95% CI, 0.54 to 1.08]; two-sided P = .126), which did not meet the criteria for statistical significance in the intent-to-treat population. Incorrect chemotherapy response stratification data for 7 (2.7%) patients were identified. In a prespecified exploratory analysis of PFS in audited stratification data, PFS for selinexor met the threshold for statistical significance (HR, 0.71; 95% CI, 0.499 to 0.996; two-sided P = .049). Furthermore, patients with the TP53 wild-type (wt) EC had a median PFS of 13.7 and 3.7 months with selinexor and placebo. The most common grade 3 treatment-related adverse events were nausea (9%), neutropenia (9%), and thrombocytopenia (7%). CONCLUSION: The significance level for PFS was only met in the audited analysis. However, a preliminary analysis of a prespecified exploratory subgroup of patients with TP53wt EC showed promising results with selinexor maintenance therapy.